CN108135863B - 用于治疗炎性和过度增殖性病况的egr1靶向分子 - Google Patents
用于治疗炎性和过度增殖性病况的egr1靶向分子 Download PDFInfo
- Publication number
- CN108135863B CN108135863B CN201680037911.9A CN201680037911A CN108135863B CN 108135863 B CN108135863 B CN 108135863B CN 201680037911 A CN201680037911 A CN 201680037911A CN 108135863 B CN108135863 B CN 108135863B
- Authority
- CN
- China
- Prior art keywords
- group
- disease
- diseases
- term
- autoimmune
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 230000003463 hyperproliferative effect Effects 0.000 title abstract description 33
- 102100023226 Early growth response protein 1 Human genes 0.000 title description 35
- 238000011282 treatment Methods 0.000 title description 30
- 230000002757 inflammatory effect Effects 0.000 title description 20
- 230000008685 targeting Effects 0.000 title description 4
- 101001049697 Homo sapiens Early growth response protein 1 Proteins 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 95
- 206010061218 Inflammation Diseases 0.000 claims abstract description 47
- 230000004054 inflammatory process Effects 0.000 claims abstract description 47
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 239000001257 hydrogen Substances 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- 206010028980 Neoplasm Diseases 0.000 claims description 29
- 239000003814 drug Substances 0.000 claims description 26
- 201000004681 Psoriasis Diseases 0.000 claims description 25
- 201000011510 cancer Diseases 0.000 claims description 20
- 125000004122 cyclic group Chemical group 0.000 claims description 20
- 201000004624 Dermatitis Diseases 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 12
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 12
- 208000027866 inflammatory disease Diseases 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 208000004434 Calcinosis Diseases 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 230000001154 acute effect Effects 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 4
- 206010012442 Dermatitis contact Diseases 0.000 claims description 4
- 208000019872 Drug Eruptions Diseases 0.000 claims description 4
- 201000008937 atopic dermatitis Diseases 0.000 claims description 4
- 208000037976 chronic inflammation Diseases 0.000 claims description 4
- 208000010247 contact dermatitis Diseases 0.000 claims description 4
- 208000002874 Acne Vulgaris Diseases 0.000 claims description 3
- 206010012456 Dermatitis exfoliative generalised Diseases 0.000 claims description 3
- 206010012468 Dermatitis herpetiformis Diseases 0.000 claims description 3
- 206010015218 Erythema multiforme Diseases 0.000 claims description 3
- 206010015226 Erythema nodosum Diseases 0.000 claims description 3
- 201000005708 Granuloma Annulare Diseases 0.000 claims description 3
- 241001303601 Rosacea Species 0.000 claims description 3
- 206010039793 Seborrhoeic dermatitis Diseases 0.000 claims description 3
- 206010042033 Stevens-Johnson syndrome Diseases 0.000 claims description 3
- 206010044223 Toxic epidermal necrolysis Diseases 0.000 claims description 3
- 231100000087 Toxic epidermal necrolysis Toxicity 0.000 claims description 3
- 206010000496 acne Diseases 0.000 claims description 3
- 208000037893 chronic inflammatory disorder Diseases 0.000 claims description 3
- 201000004700 rosacea Diseases 0.000 claims description 3
- 208000008742 seborrheic dermatitis Diseases 0.000 claims description 3
- 208000002419 toxicodendron dermatitis Diseases 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 66
- 201000010099 disease Diseases 0.000 abstract description 55
- 238000000034 method Methods 0.000 abstract description 39
- 101000641015 Homo sapiens Sterile alpha motif domain-containing protein 9 Proteins 0.000 description 46
- 102100034291 Sterile alpha motif domain-containing protein 9 Human genes 0.000 description 45
- 241000699670 Mus sp. Species 0.000 description 44
- 125000000217 alkyl group Chemical group 0.000 description 42
- 210000004027 cell Anatomy 0.000 description 35
- 239000000203 mixture Substances 0.000 description 35
- 108010051542 Early Growth Response Protein 1 Proteins 0.000 description 34
- 210000003491 skin Anatomy 0.000 description 34
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 32
- 230000014509 gene expression Effects 0.000 description 31
- 125000003118 aryl group Chemical group 0.000 description 29
- 125000000753 cycloalkyl group Chemical group 0.000 description 29
- 125000001072 heteroaryl group Chemical group 0.000 description 29
- 230000001363 autoimmune Effects 0.000 description 28
- 208000023275 Autoimmune disease Diseases 0.000 description 26
- 230000000694 effects Effects 0.000 description 24
- 239000008194 pharmaceutical composition Substances 0.000 description 24
- 206010020751 Hypersensitivity Diseases 0.000 description 23
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 21
- 125000001424 substituent group Chemical group 0.000 description 21
- 239000004480 active ingredient Substances 0.000 description 18
- 229940079593 drug Drugs 0.000 description 18
- 208000026935 allergic disease Diseases 0.000 description 17
- 238000009472 formulation Methods 0.000 description 17
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 14
- 125000003545 alkoxy group Chemical group 0.000 description 14
- 150000001412 amines Chemical class 0.000 description 14
- -1 hydroxy, mercapto Chemical class 0.000 description 14
- 125000005309 thioalkoxy group Chemical group 0.000 description 14
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 14
- 239000002246 antineoplastic agent Substances 0.000 description 13
- 125000004429 atom Chemical group 0.000 description 13
- 150000002431 hydrogen Chemical group 0.000 description 13
- 208000011580 syndromic disease Diseases 0.000 description 13
- 125000004385 trihaloalkyl group Chemical group 0.000 description 13
- 210000002950 fibroblast Anatomy 0.000 description 12
- 229910052736 halogen Inorganic materials 0.000 description 12
- 150000002367 halogens Chemical class 0.000 description 12
- 239000007924 injection Substances 0.000 description 12
- 238000002347 injection Methods 0.000 description 12
- 108090000623 proteins and genes Proteins 0.000 description 12
- 239000011734 sodium Substances 0.000 description 12
- 229910052708 sodium Inorganic materials 0.000 description 12
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 11
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 11
- 108060001084 Luciferase Proteins 0.000 description 11
- 239000005089 Luciferase Substances 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- 239000003981 vehicle Substances 0.000 description 11
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 10
- 230000007815 allergy Effects 0.000 description 10
- 229910052799 carbon Inorganic materials 0.000 description 10
- 150000004820 halides Chemical class 0.000 description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
- DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 description 10
- 229960002751 imiquimod Drugs 0.000 description 10
- 125000005647 linker group Chemical group 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 9
- 230000006378 damage Effects 0.000 description 9
- 208000035475 disorder Diseases 0.000 description 9
- 230000000762 glandular Effects 0.000 description 9
- 206010025135 lupus erythematosus Diseases 0.000 description 9
- 230000001404 mediated effect Effects 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 8
- 150000004660 O-thiocarbamates Chemical class 0.000 description 8
- 210000001744 T-lymphocyte Anatomy 0.000 description 8
- 206010052779 Transplant rejections Diseases 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 238000004113 cell culture Methods 0.000 description 8
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 125000003396 thiol group Chemical class [H]S* 0.000 description 8
- 206010008027 Cerebellar atrophy Diseases 0.000 description 7
- 208000035473 Communicable disease Diseases 0.000 description 7
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 125000004104 aryloxy group Chemical group 0.000 description 7
- 230000004071 biological effect Effects 0.000 description 7
- 239000004202 carbamide Substances 0.000 description 7
- 125000004093 cyano group Chemical group *C#N 0.000 description 7
- 229940127089 cytotoxic agent Drugs 0.000 description 7
- 239000012634 fragment Substances 0.000 description 7
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 7
- 208000015181 infectious disease Diseases 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 7
- 230000001185 psoriatic effect Effects 0.000 description 7
- 238000003762 quantitative reverse transcription PCR Methods 0.000 description 7
- 150000003462 sulfoxides Chemical class 0.000 description 7
- 125000005296 thioaryloxy group Chemical group 0.000 description 7
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 description 6
- 208000012902 Nervous system disease Diseases 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 6
- 125000003342 alkenyl group Chemical group 0.000 description 6
- 125000000304 alkynyl group Chemical group 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- CREUERHWPBNLFU-UHFFFAOYSA-N azanylidyne-[(nitrodiazenyl)sulfonylamino]methane Chemical compound [O-][N+](=O)N=NS(=O)(=O)NC#N CREUERHWPBNLFU-UHFFFAOYSA-N 0.000 description 6
- 238000001574 biopsy Methods 0.000 description 6
- 150000001721 carbon Chemical group 0.000 description 6
- 229960003957 dexamethasone Drugs 0.000 description 6
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 6
- 230000028709 inflammatory response Effects 0.000 description 6
- 201000001119 neuropathy Diseases 0.000 description 6
- 230000007823 neuropathy Effects 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- 208000033808 peripheral neuropathy Diseases 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- 108010010803 Gelatin Proteins 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 206010025323 Lymphomas Diseases 0.000 description 5
- 206010027476 Metastases Diseases 0.000 description 5
- 208000005927 Myosarcoma Diseases 0.000 description 5
- 206010029260 Neuroblastoma Diseases 0.000 description 5
- 208000027418 Wounds and injury Diseases 0.000 description 5
- 206010003246 arthritis Diseases 0.000 description 5
- 230000005784 autoimmunity Effects 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 230000001684 chronic effect Effects 0.000 description 5
- 239000006071 cream Substances 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 239000003974 emollient agent Substances 0.000 description 5
- 206010014599 encephalitis Diseases 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 229920000159 gelatin Polymers 0.000 description 5
- 239000008273 gelatin Substances 0.000 description 5
- 229940014259 gelatin Drugs 0.000 description 5
- 235000019322 gelatine Nutrition 0.000 description 5
- 235000011852 gelatine desserts Nutrition 0.000 description 5
- 125000000623 heterocyclic group Chemical group 0.000 description 5
- 230000009610 hypersensitivity Effects 0.000 description 5
- 208000014674 injury Diseases 0.000 description 5
- 230000000670 limiting effect Effects 0.000 description 5
- 239000006210 lotion Substances 0.000 description 5
- 201000002077 muscle cancer Diseases 0.000 description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 230000009885 systemic effect Effects 0.000 description 5
- 210000002435 tendon Anatomy 0.000 description 5
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 208000023328 Basedow disease Diseases 0.000 description 4
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 4
- 208000024172 Cardiovascular disease Diseases 0.000 description 4
- 208000011231 Crohn disease Diseases 0.000 description 4
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
- 208000015023 Graves' disease Diseases 0.000 description 4
- 108010050904 Interferons Proteins 0.000 description 4
- 102000014150 Interferons Human genes 0.000 description 4
- 239000004166 Lanolin Substances 0.000 description 4
- 206010028372 Muscular weakness Diseases 0.000 description 4
- 201000002481 Myositis Diseases 0.000 description 4
- 208000025966 Neurological disease Diseases 0.000 description 4
- MITFXPHMIHQXPI-UHFFFAOYSA-N Oraflex Chemical compound N=1C2=CC(C(C(O)=O)C)=CC=C2OC=1C1=CC=C(Cl)C=C1 MITFXPHMIHQXPI-UHFFFAOYSA-N 0.000 description 4
- 201000011152 Pemphigus Diseases 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 208000024799 Thyroid disease Diseases 0.000 description 4
- 108700009124 Transcription Initiation Site Proteins 0.000 description 4
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 208000018631 connective tissue disease Diseases 0.000 description 4
- 239000012990 dithiocarbamate Substances 0.000 description 4
- 239000008298 dragée Substances 0.000 description 4
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 239000000411 inducer Substances 0.000 description 4
- 229940079322 interferon Drugs 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 235000019388 lanolin Nutrition 0.000 description 4
- 229940039717 lanolin Drugs 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 230000009401 metastasis Effects 0.000 description 4
- 230000036473 myasthenia Effects 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- 239000005022 packaging material Substances 0.000 description 4
- 230000007170 pathology Effects 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 201000007094 prostatitis Diseases 0.000 description 4
- 238000001959 radiotherapy Methods 0.000 description 4
- WVYADZUPLLSGPU-UHFFFAOYSA-N salsalate Chemical compound OC(=O)C1=CC=CC=C1OC(=O)C1=CC=CC=C1O WVYADZUPLLSGPU-UHFFFAOYSA-N 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000003381 stabilizer Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 229960003676 tenidap Drugs 0.000 description 4
- LXIKEPCNDFVJKC-QXMHVHEDSA-N tenidap Chemical compound C12=CC(Cl)=CC=C2N(C(=O)N)C(=O)\C1=C(/O)C1=CC=CS1 LXIKEPCNDFVJKC-QXMHVHEDSA-N 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- 230000003612 virological effect Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 3
- YXQLOAPVCIQVBA-UHFFFAOYSA-N 7,9-dichloro-5,5-dioxo-10-propylphenothiazin-3-amine Chemical compound ClC1=CC(Cl)=C2N(CCC)C3=CC=C(N)C=C3S(=O)(=O)C2=C1 YXQLOAPVCIQVBA-UHFFFAOYSA-N 0.000 description 3
- 206010003827 Autoimmune hepatitis Diseases 0.000 description 3
- 208000031212 Autoimmune polyendocrinopathy Diseases 0.000 description 3
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 201000009030 Carcinoma Diseases 0.000 description 3
- 208000012514 Cumulative Trauma disease Diseases 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 208000017452 Epidermal disease Diseases 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 208000018522 Gastrointestinal disease Diseases 0.000 description 3
- 206010019280 Heart failures Diseases 0.000 description 3
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
- 229930182816 L-glutamine Natural products 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 206010028665 Myxoedema Diseases 0.000 description 3
- 206010028851 Necrosis Diseases 0.000 description 3
- 229930012538 Paclitaxel Natural products 0.000 description 3
- 208000002193 Pain Diseases 0.000 description 3
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 3
- 241000242739 Renilla Species 0.000 description 3
- 108010052090 Renilla Luciferases Proteins 0.000 description 3
- 206010038584 Repetitive strain injury Diseases 0.000 description 3
- 206010039710 Scleroderma Diseases 0.000 description 3
- 208000024780 Urticaria Diseases 0.000 description 3
- 206010047115 Vasculitis Diseases 0.000 description 3
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 150000007942 carboxylates Chemical group 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 229940044683 chemotherapy drug Drugs 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 230000002500 effect on skin Effects 0.000 description 3
- 210000002615 epidermis Anatomy 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 208000006454 hepatitis Diseases 0.000 description 3
- 231100000283 hepatitis Toxicity 0.000 description 3
- 229960001680 ibuprofen Drugs 0.000 description 3
- 208000026278 immune system disease Diseases 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 239000007928 intraperitoneal injection Substances 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 208000019423 liver disease Diseases 0.000 description 3
- 208000020816 lung neoplasm Diseases 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 238000010172 mouse model Methods 0.000 description 3
- 201000006417 multiple sclerosis Diseases 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 206010028417 myasthenia gravis Diseases 0.000 description 3
- 210000000822 natural killer cell Anatomy 0.000 description 3
- 230000017074 necrotic cell death Effects 0.000 description 3
- 230000002956 necrotizing effect Effects 0.000 description 3
- 230000002232 neuromuscular Effects 0.000 description 3
- 229960001592 paclitaxel Drugs 0.000 description 3
- 239000012188 paraffin wax Substances 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 229960002702 piroxicam Drugs 0.000 description 3
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000003753 real-time PCR Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 208000017520 skin disease Diseases 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 239000012453 solvate Substances 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 125000000547 substituted alkyl group Chemical group 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 230000008961 swelling Effects 0.000 description 3
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 3
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 3
- 238000011144 upstream manufacturing Methods 0.000 description 3
- KDQAABAKXDWYSZ-PNYVAJAMSA-N vinblastine sulfate Chemical compound OS(O)(=O)=O.C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 KDQAABAKXDWYSZ-PNYVAJAMSA-N 0.000 description 3
- 229960004982 vinblastine sulfate Drugs 0.000 description 3
- 230000003442 weekly effect Effects 0.000 description 3
- AUDFHJLSHQWFQQ-SFHVURJKSA-N (2s)-2-[[2-[1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetyl]amino]-3-hydroxypropanoic acid Chemical compound CC1=C(CC(=O)N[C@@H](CO)C(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 AUDFHJLSHQWFQQ-SFHVURJKSA-N 0.000 description 2
- SHCYQUDTKWHARF-UHFFFAOYSA-N (3-oxo-1h-2-benzofuran-1-yl) 2-acetyloxybenzoate Chemical compound CC(=O)OC1=CC=CC=C1C(=O)OC1C2=CC=CC=C2C(=O)O1 SHCYQUDTKWHARF-UHFFFAOYSA-N 0.000 description 2
- PPQZABOURJVKNI-UHFFFAOYSA-N (4-fluorophenyl)-[4-(4-fluorophenyl)-4-hydroxy-1-methylpiperidin-3-yl]methanone Chemical compound C1N(C)CCC(O)(C=2C=CC(F)=CC=2)C1C(=O)C1=CC=C(F)C=C1 PPQZABOURJVKNI-UHFFFAOYSA-N 0.000 description 2
- SWXOGPJRIDTIRL-DOUNNPEJSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-n-[(2s)-1-amino-3-(1h-indol-3-yl)-1-oxopropan-2-yl]-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-16-[(4-hydroxyphenyl)methyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-7-propan-2-yl-1,2-dithia-5,8,11,14,17-pent Chemical compound C([C@H]1C(=O)N[C@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](N)CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(N)=O)=O)C(C)C)C1=CC=C(O)C=C1 SWXOGPJRIDTIRL-DOUNNPEJSA-N 0.000 description 2
- MWWSFMDVAYGXBV-FGBSZODSSA-N (7s,9s)-7-[(2r,4s,5r,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione;hydron;chloride Chemical compound Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 MWWSFMDVAYGXBV-FGBSZODSSA-N 0.000 description 2
- RCFNNLSZHVHCEK-YGCMNLPTSA-N (7s,9s)-7-[(2s,4r,6s)-4-amino-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione;hydrochloride Chemical compound Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)C[C@H](C)O1 RCFNNLSZHVHCEK-YGCMNLPTSA-N 0.000 description 2
- FONKWHRXTPJODV-DNQXCXABSA-N 1,3-bis[2-[(8s)-8-(chloromethyl)-4-hydroxy-1-methyl-7,8-dihydro-3h-pyrrolo[3,2-e]indole-6-carbonyl]-1h-indol-5-yl]urea Chemical compound C1([C@H](CCl)CN2C(=O)C=3NC4=CC=C(C=C4C=3)NC(=O)NC=3C=C4C=C(NC4=CC=3)C(=O)N3C4=CC(O)=C5NC=C(C5=C4[C@H](CCl)C3)C)=C2C=C(O)C2=C1C(C)=CN2 FONKWHRXTPJODV-DNQXCXABSA-N 0.000 description 2
- YETULFFXNIHQLK-UHFFFAOYSA-N 1-ethynyl-4-(2-fluorophenyl)benzene Chemical compound FC1=CC=CC=C1C1=CC=C(C#C)C=C1 YETULFFXNIHQLK-UHFFFAOYSA-N 0.000 description 2
- CNQCTSLNJJVSAU-UHFFFAOYSA-N 132937-89-4 Chemical compound O.Cl.Cl.Cl.Cl.OCCNCCN1N=C2C3=CC=CC(O)=C3C(=O)C3=C2C1=CC=C3NCCNCCO.OCCNCCN1N=C2C3=CC=CC(O)=C3C(=O)C3=C2C1=CC=C3NCCNCCO CNQCTSLNJJVSAU-UHFFFAOYSA-N 0.000 description 2
- SRETXDDCKMOQNE-UHFFFAOYSA-N 2,3-bis(4-methoxyphenyl)-1h-indole Chemical compound C1=CC(OC)=CC=C1C1=C(C=2C=CC(OC)=CC=2)C2=CC=CC=C2N1 SRETXDDCKMOQNE-UHFFFAOYSA-N 0.000 description 2
- ODZUWQAFWMLWCF-UHFFFAOYSA-N 2-(3-phenyl-1-benzofuran-7-yl)propanoic acid Chemical compound C=1OC=2C(C(C(O)=O)C)=CC=CC=2C=1C1=CC=CC=C1 ODZUWQAFWMLWCF-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- DCXHLPGLBYHNMU-UHFFFAOYSA-N 2-[1-(4-azidobenzoyl)-5-methoxy-2-methylindol-3-yl]acetic acid Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(N=[N+]=[N-])C=C1 DCXHLPGLBYHNMU-UHFFFAOYSA-N 0.000 description 2
- IDCAZKFFVIMCCS-UHFFFAOYSA-N 2-[3-(4-chlorophenyl)-4-imino-2-oxoimidazolidin-1-yl]acetonitrile Chemical compound C1=CC(Cl)=CC=C1N1C(=O)N(CC#N)CC1=N IDCAZKFFVIMCCS-UHFFFAOYSA-N 0.000 description 2
- ANMLJLFWUCQGKZ-UHFFFAOYSA-N 2-[3-(trifluoromethyl)anilino]-3-pyridinecarboxylic acid (3-oxo-1H-isobenzofuran-1-yl) ester Chemical compound FC(F)(F)C1=CC=CC(NC=2C(=CC=CN=2)C(=O)OC2C3=CC=CC=C3C(=O)O2)=C1 ANMLJLFWUCQGKZ-UHFFFAOYSA-N 0.000 description 2
- JIEKMACRVQTPRC-UHFFFAOYSA-N 2-[4-(4-chlorophenyl)-2-phenyl-5-thiazolyl]acetic acid Chemical compound OC(=O)CC=1SC(C=2C=CC=CC=2)=NC=1C1=CC=C(Cl)C=C1 JIEKMACRVQTPRC-UHFFFAOYSA-N 0.000 description 2
- GTJXPMSTODOYNP-BTKVJIOYSA-N 3-[(e)-1-[4-[2-(dimethylamino)ethoxy]phenyl]-2-phenylbut-1-enyl]phenol;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C=1C=CC=CC=1C(/CC)=C(C=1C=C(O)C=CC=1)\C1=CC=C(OCCN(C)C)C=C1 GTJXPMSTODOYNP-BTKVJIOYSA-N 0.000 description 2
- UZFPOOOQHWICKY-UHFFFAOYSA-N 3-[13-[1-[1-[8,12-bis(2-carboxyethyl)-17-(1-hydroxyethyl)-3,7,13,18-tetramethyl-21,24-dihydroporphyrin-2-yl]ethoxy]ethyl]-18-(2-carboxyethyl)-8-(1-hydroxyethyl)-3,7,12,17-tetramethyl-22,23-dihydroporphyrin-2-yl]propanoic acid Chemical compound N1C(C=C2C(=C(CCC(O)=O)C(C=C3C(=C(C)C(C=C4N5)=N3)CCC(O)=O)=N2)C)=C(C)C(C(C)O)=C1C=C5C(C)=C4C(C)OC(C)C1=C(N2)C=C(N3)C(C)=C(C(O)C)C3=CC(C(C)=C3CCC(O)=O)=NC3=CC(C(CCC(O)=O)=C3C)=NC3=CC2=C1C UZFPOOOQHWICKY-UHFFFAOYSA-N 0.000 description 2
- QNKJFXARIMSDBR-UHFFFAOYSA-N 3-[2-[bis(2-chloroethyl)amino]ethyl]-1,3-diazaspiro[4.5]decane-2,4-dione Chemical compound O=C1N(CCN(CCCl)CCCl)C(=O)NC11CCCCC1 QNKJFXARIMSDBR-UHFFFAOYSA-N 0.000 description 2
- CLPFFLWZZBQMAO-UHFFFAOYSA-N 4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound C1=CC(C#N)=CC=C1C1N2C=NC=C2CCC1 CLPFFLWZZBQMAO-UHFFFAOYSA-N 0.000 description 2
- AKJHMTWEGVYYSE-AIRMAKDCSA-N 4-HPR Chemical compound C=1C=C(O)C=CC=1NC(=O)/C=C(\C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C AKJHMTWEGVYYSE-AIRMAKDCSA-N 0.000 description 2
- LQVMQEYROPXMQH-UHFFFAOYSA-N 4-dibenzofuran-2-yl-4-oxobutanoic acid Chemical compound C1=CC=C2C3=CC(C(=O)CCC(=O)O)=CC=C3OC2=C1 LQVMQEYROPXMQH-UHFFFAOYSA-N 0.000 description 2
- SYCHUQUJURZQMO-UHFFFAOYSA-N 4-hydroxy-2-methyl-1,1-dioxo-n-(1,3-thiazol-2-yl)-1$l^{6},2-benzothiazine-3-carboxamide Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=CS1 SYCHUQUJURZQMO-UHFFFAOYSA-N 0.000 description 2
- KYNQVALQBVIVGA-UHFFFAOYSA-N 5,11-dimethyl-6h-pyrido[4,3-b]carbazole-1-carboxamide;hydrochloride Chemical compound Cl.N1=CC=C2C(C)=C(NC=3C4=CC=CC=3)C4=C(C)C2=C1C(N)=O KYNQVALQBVIVGA-UHFFFAOYSA-N 0.000 description 2
- HEOZYYOUKGGSBJ-UHFFFAOYSA-N 5-(4-methoxybenzoyl)-2,3-dihydro-1h-pyrrolizine-1-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C(=O)C1=CC=C2N1CCC2C(O)=O HEOZYYOUKGGSBJ-UHFFFAOYSA-N 0.000 description 2
- IDPUKCWIGUEADI-UHFFFAOYSA-N 5-[bis(2-chloroethyl)amino]uracil Chemical compound ClCCN(CCCl)C1=CNC(=O)NC1=O IDPUKCWIGUEADI-UHFFFAOYSA-N 0.000 description 2
- WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 2
- VHRSUDSXCMQTMA-PJHHCJLFSA-N 6alpha-methylprednisolone Chemical compound C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)CO)CC[C@H]21 VHRSUDSXCMQTMA-PJHHCJLFSA-N 0.000 description 2
- LPDLEICKXUVJHW-QJILNLRNSA-N 78nz2pmp25 Chemical compound OS(O)(=O)=O.O([C@]12[C@H](OC(C)=O)[C@]3(CC)C=CCN4CC[C@@]5([C@H]34)[C@H]1N(C)C1=C5C=C(C(=C1)OC)[C@]1(C(=O)OC)C3=C(C4=CC=CC=C4N3)CCN3C[C@H](C1)C[C@@](C3)(O)CC)C(=O)N(CCCl)C2=O LPDLEICKXUVJHW-QJILNLRNSA-N 0.000 description 2
- 206010000871 Acute monocytic leukaemia Diseases 0.000 description 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- 206010001935 American trypanosomiasis Diseases 0.000 description 2
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 2
- 244000105975 Antidesma platyphyllum Species 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 208000035143 Bacterial infection Diseases 0.000 description 2
- 206010005003 Bladder cancer Diseases 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical group NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 208000024699 Chagas disease Diseases 0.000 description 2
- JWBOIMRXGHLCPP-UHFFFAOYSA-N Chloditan Chemical compound C=1C=CC=C(Cl)C=1C(C(Cl)Cl)C1=CC=C(Cl)C=C1 JWBOIMRXGHLCPP-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 206010008748 Chorea Diseases 0.000 description 2
- 206010008909 Chronic Hepatitis Diseases 0.000 description 2
- KATBVKFXGKGUFE-UHFFFAOYSA-N Cintazone Chemical compound C12=CC=CC=C2N2C(=O)C(CCCCC)C(=O)N2C=C1C1=CC=CC=C1 KATBVKFXGKGUFE-UHFFFAOYSA-N 0.000 description 2
- PPASFTRHCXASPY-UHFFFAOYSA-N Cl.Cl.NCCCNc1ccc2c3c(nn2CCNCCO)c4c(O)ccc(O)c4C(=O)c13 Chemical compound Cl.Cl.NCCCNc1ccc2c3c(nn2CCNCCO)c4c(O)ccc(O)c4C(=O)c13 PPASFTRHCXASPY-UHFFFAOYSA-N 0.000 description 2
- 208000015943 Coeliac disease Diseases 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 206010010356 Congenital anomaly Diseases 0.000 description 2
- 206010011732 Cyst Diseases 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 108010092160 Dactinomycin Proteins 0.000 description 2
- 101000582926 Dictyostelium discoideum Probable serine/threonine-protein kinase PLK Proteins 0.000 description 2
- WYQPLTPSGFELIB-JTQPXKBDSA-N Difluprednate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2CC[C@@](C(=O)COC(C)=O)(OC(=O)CCC)[C@@]2(C)C[C@@H]1O WYQPLTPSGFELIB-JTQPXKBDSA-N 0.000 description 2
- ZQZFYGIXNQKOAV-OCEACIFDSA-N Droloxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=C(O)C=CC=1)\C1=CC=C(OCCN(C)C)C=C1 ZQZFYGIXNQKOAV-OCEACIFDSA-N 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 206010015150 Erythema Diseases 0.000 description 2
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 description 2
- 206010018364 Glomerulonephritis Diseases 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- 208000008899 Habitual abortion Diseases 0.000 description 2
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 2
- 208000027761 Hepatic autoimmune disease Diseases 0.000 description 2
- 206010019755 Hepatitis chronic active Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- 102100040018 Interferon alpha-2 Human genes 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 229930126263 Maytansine Natural products 0.000 description 2
- 208000035489 Monocytic Acute Leukemia Diseases 0.000 description 2
- 208000029578 Muscle disease Diseases 0.000 description 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
- LYPFDBRUNKHDGX-SOGSVHMOSA-N N1C2=CC=C1\C(=C1\C=CC(=N1)\C(=C1\C=C/C(/N1)=C(/C1=N/C(/CC1)=C2/C1=CC(O)=CC=C1)C1=CC(O)=CC=C1)\C1=CC(O)=CC=C1)C1=CC(O)=CC=C1 Chemical compound N1C2=CC=C1\C(=C1\C=CC(=N1)\C(=C1\C=C/C(/N1)=C(/C1=N/C(/CC1)=C2/C1=CC(O)=CC=C1)C1=CC(O)=CC=C1)\C1=CC(O)=CC=C1)C1=CC(O)=CC=C1 LYPFDBRUNKHDGX-SOGSVHMOSA-N 0.000 description 2
- 229930193140 Neomycin Natural products 0.000 description 2
- 206010029240 Neuritis Diseases 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 208000003435 Optic Neuritis Diseases 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 description 2
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
- 208000030852 Parasitic disease Diseases 0.000 description 2
- 206010034277 Pemphigoid Diseases 0.000 description 2
- 208000027086 Pemphigus foliaceus Diseases 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- HFVNWDWLWUCIHC-GUPDPFMOSA-N Prednimustine Chemical compound O=C([C@@]1(O)CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)[C@@H](O)C[C@@]21C)COC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 HFVNWDWLWUCIHC-GUPDPFMOSA-N 0.000 description 2
- 239000005822 Propiconazole Substances 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 206010071141 Rasmussen encephalitis Diseases 0.000 description 2
- 208000004160 Rasmussen subacute encephalitis Diseases 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 238000011579 SCID mouse model Methods 0.000 description 2
- OTKJDMGTUTTYMP-ROUUACIJSA-N Safingol ( L-threo-sphinganine) Chemical compound CCCCCCCCCCCCCCC[C@H](O)[C@@H](N)CO OTKJDMGTUTTYMP-ROUUACIJSA-N 0.000 description 2
- 206010048908 Seasonal allergy Diseases 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- 206010072148 Stiff-Person syndrome Diseases 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 201000009594 Systemic Scleroderma Diseases 0.000 description 2
- 208000018359 Systemic autoimmune disease Diseases 0.000 description 2
- 206010042953 Systemic sclerosis Diseases 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 2
- 206010043561 Thrombocytopenic purpura Diseases 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 208000000323 Tourette Syndrome Diseases 0.000 description 2
- 208000016620 Tourette disease Diseases 0.000 description 2
- 241000223109 Trypanosoma cruzi Species 0.000 description 2
- 206010045240 Type I hypersensitivity Diseases 0.000 description 2
- 206010054000 Type II hypersensitivity Diseases 0.000 description 2
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 2
- QPWBZVAOCWJTFK-UHFFFAOYSA-L [2-(azanidylmethyl)-3-hydroxy-2-(hydroxymethyl)propyl]azanide;cyclobutane-1,1-dicarboxylate;platinum(4+) Chemical compound [Pt+4].[NH-]CC(C[NH-])(CO)CO.[O-]C(=O)C1(C([O-])=O)CCC1 QPWBZVAOCWJTFK-UHFFFAOYSA-L 0.000 description 2
- NAFFDQVVNWTDJD-UHFFFAOYSA-L [4-(azanidylmethyl)oxan-4-yl]methylazanide;cyclobutane-1,1-dicarboxylate;platinum(4+) Chemical compound [Pt+4].[NH-]CC1(C[NH-])CCOCC1.[O-]C(=O)C1(C([O-])=O)CCC1 NAFFDQVVNWTDJD-UHFFFAOYSA-L 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 229930183665 actinomycin Natural products 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
- 208000009956 adenocarcinoma Diseases 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 229950004955 adozelesin Drugs 0.000 description 2
- BYRVKDUQDLJUBX-JJCDCTGGSA-N adozelesin Chemical compound C1=CC=C2OC(C(=O)NC=3C=C4C=C(NC4=CC=3)C(=O)N3C[C@H]4C[C@]44C5=C(C(C=C43)=O)NC=C5C)=CC2=C1 BYRVKDUQDLJUBX-JJCDCTGGSA-N 0.000 description 2
- 229960004229 alclometasone dipropionate Drugs 0.000 description 2
- DJHCCTTVDRAMEH-DUUJBDRPSA-N alclometasone dipropionate Chemical compound C([C@H]1Cl)C2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)COC(=O)CC)(OC(=O)CC)[C@@]1(C)C[C@@H]2O DJHCCTTVDRAMEH-DUUJBDRPSA-N 0.000 description 2
- 108700025316 aldesleukin Proteins 0.000 description 2
- 229960005310 aldesleukin Drugs 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 150000001345 alkine derivatives Chemical class 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 2
- QZNJPJDUBTYMRS-UHFFFAOYSA-M amfenac sodium hydrate Chemical compound O.[Na+].NC1=C(CC([O-])=O)C=CC=C1C(=O)C1=CC=CC=C1 QZNJPJDUBTYMRS-UHFFFAOYSA-M 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 125000004103 aminoalkyl group Chemical group 0.000 description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 229950004699 anirolac Drugs 0.000 description 2
- HDNJXZZJFPCFHG-UHFFFAOYSA-N anitrazafen Chemical compound C1=CC(OC)=CC=C1C1=NN=C(C)N=C1C1=CC=C(OC)C=C1 HDNJXZZJFPCFHG-UHFFFAOYSA-N 0.000 description 2
- 229950002412 anitrazafen Drugs 0.000 description 2
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
- 230000003432 anti-folate effect Effects 0.000 description 2
- 230000000469 anti-sperm effect Effects 0.000 description 2
- 229940127074 antifolate Drugs 0.000 description 2
- 238000002617 apheresis Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 206010003230 arteritis Diseases 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 208000010216 atopic IgE responsiveness Diseases 0.000 description 2
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 2
- 201000004339 autoimmune neuropathy Diseases 0.000 description 2
- 208000010928 autoimmune thyroid disease Diseases 0.000 description 2
- 229960001671 azapropazone Drugs 0.000 description 2
- WOIIIUDZSOLAIW-NSHDSACASA-N azapropazone Chemical compound C1=C(C)C=C2N3C(=O)[C@H](CC=C)C(=O)N3C(N(C)C)=NC2=C1 WOIIIUDZSOLAIW-NSHDSACASA-N 0.000 description 2
- HRXVDDOKERXBEY-UHFFFAOYSA-N azatepa Chemical compound C1CN1P(=O)(N1CC1)N(CC)C1=NN=CS1 HRXVDDOKERXBEY-UHFFFAOYSA-N 0.000 description 2
- XFILPEOLDIKJHX-QYZOEREBSA-N batimastat Chemical compound C([C@@H](C(=O)NC)NC(=O)[C@H](CC(C)C)[C@H](CSC=1SC=CC=1)C(=O)NO)C1=CC=CC=C1 XFILPEOLDIKJHX-QYZOEREBSA-N 0.000 description 2
- 229950001858 batimastat Drugs 0.000 description 2
- 229960005430 benoxaprofen Drugs 0.000 description 2
- MMIMIFULGMZVPO-UHFFFAOYSA-N benzyl 3-bromo-2,6-dinitro-5-phenylmethoxybenzoate Chemical compound [O-][N+](=O)C1=C(C(=O)OCC=2C=CC=CC=2)C([N+](=O)[O-])=C(Br)C=C1OCC1=CC=CC=C1 MMIMIFULGMZVPO-UHFFFAOYSA-N 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- QRZAKQDHEVVFRX-UHFFFAOYSA-N biphenyl-4-ylacetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1C1=CC=CC=C1 QRZAKQDHEVVFRX-UHFFFAOYSA-N 0.000 description 2
- 229950006844 bizelesin Drugs 0.000 description 2
- 208000026555 breast adenosis Diseases 0.000 description 2
- PZOHOALJQOFNTB-UHFFFAOYSA-M brequinar sodium Chemical compound [Na+].N1=C2C=CC(F)=CC2=C(C([O-])=O)C(C)=C1C(C=C1)=CC=C1C1=CC=CC=C1F PZOHOALJQOFNTB-UHFFFAOYSA-M 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 208000000594 bullous pemphigoid Diseases 0.000 description 2
- 230000002308 calcification Effects 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 229950010667 cedefingol Drugs 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 208000012601 choreatic disease Diseases 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 208000031513 cyst Diseases 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 description 2
- 229960000616 diflunisal Drugs 0.000 description 2
- 229960004875 difluprednate Drugs 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 208000032625 disorder of ear Diseases 0.000 description 2
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 2
- 229960004679 doxorubicin Drugs 0.000 description 2
- 229950004203 droloxifene Drugs 0.000 description 2
- NOTIQUSPUUHHEH-UXOVVSIBSA-N dromostanolone propionate Chemical compound C([C@@H]1CC2)C(=O)[C@H](C)C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](OC(=O)CC)[C@@]2(C)CC1 NOTIQUSPUUHHEH-UXOVVSIBSA-N 0.000 description 2
- 229950004683 drostanolone propionate Drugs 0.000 description 2
- MGQRRMONVLMKJL-KWJIQSIXSA-N elsamitrucin Chemical compound O1[C@H](C)[C@H](O)[C@H](OC)[C@@H](N)[C@H]1O[C@@H]1[C@](O)(C)[C@@H](O)[C@@H](C)O[C@H]1OC1=CC=CC2=C(O)C(C(O3)=O)=C4C5=C3C=CC(C)=C5C(=O)OC4=C12 MGQRRMONVLMKJL-KWJIQSIXSA-N 0.000 description 2
- 229950002339 elsamitrucin Drugs 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 229950010625 enloplatin Drugs 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 229950001426 erbulozole Drugs 0.000 description 2
- KLEPCGBEXOCIGS-QPPBQGQZSA-N erbulozole Chemical compound C1=CC(NC(=O)OCC)=CC=C1SC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C=CC(OC)=CC=2)OC1 KLEPCGBEXOCIGS-QPPBQGQZSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- WCDWBPCFGJXFJZ-UHFFFAOYSA-N etanidazole Chemical compound OCCNC(=O)CN1C=CN=C1[N+]([O-])=O WCDWBPCFGJXFJZ-UHFFFAOYSA-N 0.000 description 2
- 229950006566 etanidazole Drugs 0.000 description 2
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229950011548 fadrozole Drugs 0.000 description 2
- 239000010685 fatty oil Substances 0.000 description 2
- NMUSYJAQQFHJEW-ARQDHWQXSA-N fazarabine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-ARQDHWQXSA-N 0.000 description 2
- 229950005096 fazarabine Drugs 0.000 description 2
- 229960000192 felbinac Drugs 0.000 description 2
- IDKAXRLETRCXKS-UHFFFAOYSA-N fenclofenac Chemical compound OC(=O)CC1=CC=CC=C1OC1=CC=C(Cl)C=C1Cl IDKAXRLETRCXKS-UHFFFAOYSA-N 0.000 description 2
- 229950006236 fenclofenac Drugs 0.000 description 2
- 229950003662 fenretinide Drugs 0.000 description 2
- 229960002679 fentiazac Drugs 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 229950004322 flazalone Drugs 0.000 description 2
- WEGNFRKBIKYVLC-XTLNBZDDSA-N flunisolide acetate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)COC(=O)C)[C@@]2(C)C[C@@H]1O WEGNFRKBIKYVLC-XTLNBZDDSA-N 0.000 description 2
- 229960000588 flunixin Drugs 0.000 description 2
- NOOCSNJCXJYGPE-UHFFFAOYSA-N flunixin Chemical compound C1=CC=C(C(F)(F)F)C(C)=C1NC1=NC=CC=C1C(O)=O NOOCSNJCXJYGPE-UHFFFAOYSA-N 0.000 description 2
- MGCCHNLNRBULBU-WZTVWXICSA-N flunixin meglumine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.C1=CC=C(C(F)(F)F)C(C)=C1NC1=NC=CC=C1C(O)=O MGCCHNLNRBULBU-WZTVWXICSA-N 0.000 description 2
- 229960000469 flunixin meglumine Drugs 0.000 description 2
- 229950003750 fluretofen Drugs 0.000 description 2
- 239000004052 folic acid antagonist Substances 0.000 description 2
- 229950008156 furaprofen Drugs 0.000 description 2
- 229950006099 furobufen Drugs 0.000 description 2
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 235000009424 haa Nutrition 0.000 description 2
- 239000007902 hard capsule Substances 0.000 description 2
- 210000002443 helper t lymphocyte Anatomy 0.000 description 2
- 208000007475 hemolytic anemia Diseases 0.000 description 2
- 238000013537 high throughput screening Methods 0.000 description 2
- 238000007489 histopathology method Methods 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- CYWFCPPBTWOZSF-UHFFFAOYSA-N ibufenac Chemical compound CC(C)CC1=CC=C(CC(O)=O)C=C1 CYWFCPPBTWOZSF-UHFFFAOYSA-N 0.000 description 2
- 229950009183 ibufenac Drugs 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 229950008443 indoxole Drugs 0.000 description 2
- 208000000509 infertility Diseases 0.000 description 2
- 231100000535 infertility Toxicity 0.000 description 2
- 230000036512 infertility Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 201000006334 interstitial nephritis Diseases 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 229950010897 iproplatin Drugs 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- QFGMXJOBTNZHEL-UHFFFAOYSA-N isoxepac Chemical compound O1CC2=CC=CC=C2C(=O)C2=CC(CC(=O)O)=CC=C21 QFGMXJOBTNZHEL-UHFFFAOYSA-N 0.000 description 2
- 229950011455 isoxepac Drugs 0.000 description 2
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 2
- 229960000991 ketoprofen Drugs 0.000 description 2
- 208000017169 kidney disease Diseases 0.000 description 2
- 239000004922 lacquer Substances 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- DMKSVUSAATWOCU-HROMYWEYSA-N loteprednol etabonate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)OCCl)(OC(=O)OCC)[C@@]1(C)C[C@@H]2O DMKSVUSAATWOCU-HROMYWEYSA-N 0.000 description 2
- 229960003744 loteprednol etabonate Drugs 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- WKPWGQKGSOKKOO-RSFHAFMBSA-N maytansine Chemical compound CO[C@@H]([C@@]1(O)C[C@](OC(=O)N1)([C@H]([C@@H]1O[C@@]1(C)[C@@H](OC(=O)[C@H](C)N(C)C(C)=O)CC(=O)N1C)C)[H])\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 WKPWGQKGSOKKOO-RSFHAFMBSA-N 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 229960004584 methylprednisolone Drugs 0.000 description 2
- 206010063344 microscopic polyangiitis Diseases 0.000 description 2
- 229950002137 mitocarcin Drugs 0.000 description 2
- 229960000350 mitotane Drugs 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- CRJGESKKUOMBCT-PMACEKPBSA-N n-[(2s,3s)-1,3-dihydroxyoctadecan-2-yl]acetamide Chemical compound CCCCCCCCCCCCCCC[C@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-PMACEKPBSA-N 0.000 description 2
- LTRANDSQVZFZDG-SNVBAGLBSA-N naproxol Chemical compound C1=C([C@H](C)CO)C=CC2=CC(OC)=CC=C21 LTRANDSQVZFZDG-SNVBAGLBSA-N 0.000 description 2
- 229950006890 naproxol Drugs 0.000 description 2
- 229960004927 neomycin Drugs 0.000 description 2
- 230000001613 neoplastic effect Effects 0.000 description 2
- 201000008383 nephritis Diseases 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 230000000926 neurological effect Effects 0.000 description 2
- 229950006046 nimazone Drugs 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 230000002611 ovarian Effects 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 201000002528 pancreatic cancer Diseases 0.000 description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 201000001976 pemphigus vulgaris Diseases 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- NJBFOOCLYDNZJN-UHFFFAOYSA-N pipobroman Chemical compound BrCCC(=O)N1CCN(C(=O)CCBr)CC1 NJBFOOCLYDNZJN-UHFFFAOYSA-N 0.000 description 2
- 229960000952 pipobroman Drugs 0.000 description 2
- 229960000851 pirprofen Drugs 0.000 description 2
- PIDSZXPFGCURGN-UHFFFAOYSA-N pirprofen Chemical compound ClC1=CC(C(C(O)=O)C)=CC=C1N1CC=CC1 PIDSZXPFGCURGN-UHFFFAOYSA-N 0.000 description 2
- 229960004293 porfimer sodium Drugs 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 229960004694 prednimustine Drugs 0.000 description 2
- 229960001586 procarbazine hydrochloride Drugs 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- STJLVHWMYQXCPB-UHFFFAOYSA-N propiconazole Chemical compound O1C(CCC)COC1(C=1C(=CC(Cl)=CC=1)Cl)CN1N=CN=C1 STJLVHWMYQXCPB-UHFFFAOYSA-N 0.000 description 2
- OLTAWOVKGWWERU-UHFFFAOYSA-N proxazole Chemical compound C=1C=CC=CC=1C(CC)C1=NOC(CCN(CC)CC)=N1 OLTAWOVKGWWERU-UHFFFAOYSA-N 0.000 description 2
- 229960001801 proxazole Drugs 0.000 description 2
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
- 229960001487 rimexolone Drugs 0.000 description 2
- QTTRZHGPGKRAFB-OOKHYKNYSA-N rimexolone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CC)(C)[C@@]1(C)C[C@@H]2O QTTRZHGPGKRAFB-OOKHYKNYSA-N 0.000 description 2
- 229960000953 salsalate Drugs 0.000 description 2
- 210000004761 scalp Anatomy 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 229950006250 sermetacin Drugs 0.000 description 2
- 210000002460 smooth muscle Anatomy 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 229950006050 spiromustine Drugs 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- PVYJZLYGTZKPJE-UHFFFAOYSA-N streptonigrin Chemical compound C=1C=C2C(=O)C(OC)=C(N)C(=O)C2=NC=1C(C=1N)=NC(C(O)=O)=C(C)C=1C1=CC=C(OC)C(OC)=C1O PVYJZLYGTZKPJE-UHFFFAOYSA-N 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 229950005175 sudoxicam Drugs 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 229940124530 sulfonamide Drugs 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 229960005262 talniflumate Drugs 0.000 description 2
- 229950005400 talosalate Drugs 0.000 description 2
- URLYINUFLXOMHP-HTVVRFAVSA-N tcn-p Chemical compound C=12C3=NC=NC=1N(C)N=C(N)C2=CN3[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O URLYINUFLXOMHP-HTVVRFAVSA-N 0.000 description 2
- 229960002197 temoporfin Drugs 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 229960001196 thiotepa Drugs 0.000 description 2
- 208000021510 thyroid gland disease Diseases 0.000 description 2
- 206010043778 thyroiditis Diseases 0.000 description 2
- MNRILEROXIRVNJ-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=NC=N[C]21 MNRILEROXIRVNJ-UHFFFAOYSA-N 0.000 description 2
- 229960003087 tioguanine Drugs 0.000 description 2
- BISFDZNIUZIKJD-XDANTLIUSA-N tixocortol pivalate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)CSC(=O)C(C)(C)C)(O)[C@@]1(C)C[C@@H]2O BISFDZNIUZIKJD-XDANTLIUSA-N 0.000 description 2
- 229960003114 tixocortol pivalate Drugs 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 230000037317 transdermal delivery Effects 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical group [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 230000001960 triggered effect Effects 0.000 description 2
- 230000008026 type II hypersensitivity Effects 0.000 description 2
- 229960001055 uracil mustard Drugs 0.000 description 2
- 201000005112 urinary bladder cancer Diseases 0.000 description 2
- 229960002730 vapreotide Drugs 0.000 description 2
- 108700029852 vapreotide Proteins 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 229960002166 vinorelbine tartrate Drugs 0.000 description 2
- GBABOYUKABKIAF-IWWDSPBFSA-N vinorelbinetartrate Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC(C23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-IWWDSPBFSA-N 0.000 description 2
- 229960001771 vorozole Drugs 0.000 description 2
- XLMPPFTZALNBFS-INIZCTEOSA-N vorozole Chemical compound C1([C@@H](C2=CC=C3N=NN(C3=C2)C)N2N=CN=C2)=CC=C(Cl)C=C1 XLMPPFTZALNBFS-INIZCTEOSA-N 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- 229950003017 zeniplatin Drugs 0.000 description 2
- 229950007802 zidometacin Drugs 0.000 description 2
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical group C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 description 1
- HZSBSRAVNBUZRA-RQDPQJJXSA-J (1r,2r)-cyclohexane-1,2-diamine;tetrachloroplatinum(2+) Chemical compound Cl[Pt+2](Cl)(Cl)Cl.N[C@@H]1CCCC[C@H]1N HZSBSRAVNBUZRA-RQDPQJJXSA-J 0.000 description 1
- MNHVIVWFCMBFCV-AVGNSLFASA-N (2S)-2-[[(2S)-2-[[(4S)-4-amino-4-carboxybutanoyl]amino]-6-diazo-5-oxohexanoyl]amino]-6-diazo-5-oxohexanoic acid Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CCC(=O)C=[N+]=[N-])C(=O)N[C@@H](CCC(=O)C=[N+]=[N-])C(O)=O MNHVIVWFCMBFCV-AVGNSLFASA-N 0.000 description 1
- RJMIEHBSYVWVIN-LLVKDONJSA-N (2r)-2-[4-(3-oxo-1h-isoindol-2-yl)phenyl]propanoic acid Chemical compound C1=CC([C@H](C(O)=O)C)=CC=C1N1C(=O)C2=CC=CC=C2C1 RJMIEHBSYVWVIN-LLVKDONJSA-N 0.000 description 1
- PAYBYKKERMGTSS-MNCSTQPFSA-N (2r,3r,3as,9ar)-7-fluoro-2-(hydroxymethyl)-6-imino-2,3,3a,9a-tetrahydrofuro[1,2][1,3]oxazolo[3,4-a]pyrimidin-3-ol Chemical compound N=C1C(F)=CN2[C@@H]3O[C@H](CO)[C@@H](O)[C@@H]3OC2=N1 PAYBYKKERMGTSS-MNCSTQPFSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- MDKGKXOCJGEUJW-VIFPVBQESA-N (2s)-2-[4-(thiophene-2-carbonyl)phenyl]propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C(=O)C1=CC=CS1 MDKGKXOCJGEUJW-VIFPVBQESA-N 0.000 description 1
- NAALWFYYHHJEFQ-ZASNTINBSA-N (2s,5r,6r)-6-[[(2r)-2-[[6-[4-[bis(2-hydroxyethyl)sulfamoyl]phenyl]-2-oxo-1h-pyridine-3-carbonyl]amino]-2-(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound N([C@@H](C(=O)N[C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C=1C=CC(O)=CC=1)C(=O)C(C(N1)=O)=CC=C1C1=CC=C(S(=O)(=O)N(CCO)CCO)C=C1 NAALWFYYHHJEFQ-ZASNTINBSA-N 0.000 description 1
- XYRIRLDHOQSNLW-UHFFFAOYSA-N (3-oxo-1h-2-benzofuran-1-yl) 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetate Chemical compound CC1=C(CC(=O)OC2C3=CC=CC=C3C(=O)O2)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 XYRIRLDHOQSNLW-UHFFFAOYSA-N 0.000 description 1
- BVNJBATUHVXZKP-QXMHVHEDSA-N (3z)-6-chloro-5-fluoro-3-[hydroxy(thiophen-2-yl)methylidene]-2-oxoindole-1-carboxamide Chemical compound C12=CC(F)=C(Cl)C=C2N(C(=O)N)C(=O)\C1=C(/O)C1=CC=CS1 BVNJBATUHVXZKP-QXMHVHEDSA-N 0.000 description 1
- YJGVMLPVUAXIQN-LGWHJFRWSA-N (5s,5ar,8ar,9r)-5-hydroxy-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5h-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-LGWHJFRWSA-N 0.000 description 1
- OMJKFYKNWZZKTK-POHAHGRESA-N (5z)-5-(dimethylaminohydrazinylidene)imidazole-4-carboxamide Chemical compound CN(C)N\N=C1/N=CN=C1C(N)=O OMJKFYKNWZZKTK-POHAHGRESA-N 0.000 description 1
- VDNZZIYSCXESNI-ILSZZQPISA-N (6s,8s,9s,10r,11s,13s,14s,17s)-17-acetyl-11-hydroxy-6,10,13-trimethyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-one Chemical compound C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@H](C(C)=O)CC[C@H]21 VDNZZIYSCXESNI-ILSZZQPISA-N 0.000 description 1
- HMLGSIZOMSVISS-ONJSNURVSA-N (7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-(2,2-dimethylpropanoyloxymethoxyimino)acetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N([C@@H]1C(N2C(=C(C=C)CSC21)C(O)=O)=O)C(=O)\C(=N/OCOC(=O)C(C)(C)C)C1=CSC(N)=N1 HMLGSIZOMSVISS-ONJSNURVSA-N 0.000 description 1
- WYVYEIZFAUXWKW-TTYSTUCBSA-N (7s,9s)-9-acetyl-7-(4-amino-5-hydroxy-6-methyloxan-2-yl)oxy-4,6,9,11-tetrahydroxy-8,10-dihydro-7h-tetracene-5,12-dione;hydrochloride Chemical compound Cl.C1C(N)C(O)C(C)OC1O[C@@H]1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 WYVYEIZFAUXWKW-TTYSTUCBSA-N 0.000 description 1
- LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 description 1
- OJRZEKJECRTBPJ-NGAMADIESA-N (z,5s)-5-acetamido-1-diazonio-6-hydroxy-6-oxohex-1-en-2-olate Chemical compound CC(=O)N[C@H](C(O)=O)CC\C([O-])=C\[N+]#N OJRZEKJECRTBPJ-NGAMADIESA-N 0.000 description 1
- DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
- OUPZKGBUJRBPGC-HLTSFMKQSA-N 1,5-bis[[(2r)-oxiran-2-yl]methyl]-3-[[(2s)-oxiran-2-yl]methyl]-1,3,5-triazinane-2,4,6-trione Chemical compound O=C1N(C[C@H]2OC2)C(=O)N(C[C@H]2OC2)C(=O)N1C[C@H]1CO1 OUPZKGBUJRBPGC-HLTSFMKQSA-N 0.000 description 1
- UOAFGUOASVSLPK-UHFFFAOYSA-N 1-(2-chloroethyl)-3-(2,2-dimethylpropyl)-1-nitrosourea Chemical compound CC(C)(C)CNC(=O)N(N=O)CCCl UOAFGUOASVSLPK-UHFFFAOYSA-N 0.000 description 1
- JQJSFAJISYZPER-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-(2,3-dihydro-1h-inden-5-ylsulfonyl)urea Chemical compound C1=CC(Cl)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(CCC2)C2=C1 JQJSFAJISYZPER-UHFFFAOYSA-N 0.000 description 1
- ZKFNOUUKULVDOB-UHFFFAOYSA-N 1-amino-1-phenylmethyl phosphonic acid Chemical compound OP(=O)(O)C(N)C1=CC=CC=C1 ZKFNOUUKULVDOB-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- ULIDRMKBVYYVIQ-UHFFFAOYSA-N 1-phenyltetrazol-5-amine Chemical compound NC1=NN=NN1C1=CC=CC=C1 ULIDRMKBVYYVIQ-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- PBOAGYSGWIHKHA-UHFFFAOYSA-N 2,2,2-trifluoroethyl carbamate Chemical compound NC(=O)OCC(F)(F)F PBOAGYSGWIHKHA-UHFFFAOYSA-N 0.000 description 1
- VKDGNNYJFSHYKD-UHFFFAOYSA-N 2,5-diamino-2-(difluoromethyl)pentanoic acid;hydron;chloride Chemical compound Cl.NCCCC(N)(C(F)F)C(O)=O VKDGNNYJFSHYKD-UHFFFAOYSA-N 0.000 description 1
- KLIVRBFRQSOGQI-UHFFFAOYSA-N 2-(11-oxo-6h-benzo[c][1]benzothiepin-3-yl)acetic acid Chemical compound S1CC2=CC=CC=C2C(=O)C2=CC=C(CC(=O)O)C=C12 KLIVRBFRQSOGQI-UHFFFAOYSA-N 0.000 description 1
- XILVEPYQJIOVNB-UHFFFAOYSA-N 2-[3-(trifluoromethyl)anilino]benzoic acid 2-(2-hydroxyethoxy)ethyl ester Chemical compound OCCOCCOC(=O)C1=CC=CC=C1NC1=CC=CC(C(F)(F)F)=C1 XILVEPYQJIOVNB-UHFFFAOYSA-N 0.000 description 1
- NLGUJWNOGYWZBI-UHFFFAOYSA-N 2-[3-chloro-4-(thiophene-2-carbonyl)phenyl]propanoic acid Chemical compound ClC1=CC(C(C(O)=O)C)=CC=C1C(=O)C1=CC=CS1 NLGUJWNOGYWZBI-UHFFFAOYSA-N 0.000 description 1
- QKKLKGVIECOSRM-CODXZCKSSA-N 2-[4-[3-(2-chlorophenothiazin-10-yl)propyl]piperazin-1-yl]ethanol;4-[2-[(8s,9s,10r,11s,13s,14s,17r)-11,17-dihydroxy-10,13-dimethyl-3-oxo-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthren-17-yl]-2-oxoethoxy]-4-oxobutanoic acid Chemical compound C1CN(CCO)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21.O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)COC(=O)CCC(O)=O)[C@@H]4[C@@H]3CCC2=C1 QKKLKGVIECOSRM-CODXZCKSSA-N 0.000 description 1
- LNXXSBRGLBOASF-UHFFFAOYSA-N 2-[[2-(4-chlorophenyl)-4-methyl-1,3-oxazol-5-yl]methoxy]-2-methylpropanoic acid Chemical compound O1C(COC(C)(C)C(O)=O)=C(C)N=C1C1=CC=C(Cl)C=C1 LNXXSBRGLBOASF-UHFFFAOYSA-N 0.000 description 1
- QCXJFISCRQIYID-IAEPZHFASA-N 2-amino-1-n-[(3s,6s,7r,10s,16s)-3-[(2s)-butan-2-yl]-7,11,14-trimethyl-2,5,9,12,15-pentaoxo-10-propan-2-yl-8-oxa-1,4,11,14-tetrazabicyclo[14.3.0]nonadecan-6-yl]-4,6-dimethyl-3-oxo-9-n-[(3s,6s,7r,10s,16s)-7,11,14-trimethyl-2,5,9,12,15-pentaoxo-3,10-di(propa Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N=C2C(C(=O)N[C@@H]3C(=O)N[C@H](C(N4CCC[C@H]4C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]3C)=O)[C@@H](C)CC)=C(N)C(=O)C(C)=C2O2)C2=C(C)C=C1 QCXJFISCRQIYID-IAEPZHFASA-N 0.000 description 1
- GXEUNRBWEAIPCN-UHFFFAOYSA-N 2-chloro-2-(3-chloro-4-cyclohexylphenyl)acetic acid Chemical compound ClC1=CC(C(Cl)C(=O)O)=CC=C1C1CCCCC1 GXEUNRBWEAIPCN-UHFFFAOYSA-N 0.000 description 1
- LNFZAUNJFRYZLE-UHFFFAOYSA-N 2-fluoro-1h-imidazole Chemical compound FC1=NC=CN1 LNFZAUNJFRYZLE-UHFFFAOYSA-N 0.000 description 1
- HZLCGUXUOFWCCN-UHFFFAOYSA-N 2-hydroxynonadecane-1,2,3-tricarboxylic acid Chemical compound CCCCCCCCCCCCCCCCC(C(O)=O)C(O)(C(O)=O)CC(O)=O HZLCGUXUOFWCCN-UHFFFAOYSA-N 0.000 description 1
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 1
- DSWLRNLRVBAVFC-UHFFFAOYSA-N 2-methylsulfinyl-1-pyridin-2-ylethanone Chemical compound CS(=O)CC(=O)C1=CC=CC=N1 DSWLRNLRVBAVFC-UHFFFAOYSA-N 0.000 description 1
- YZEUHQHUFTYLPH-UHFFFAOYSA-N 2-nitroimidazole Chemical compound [O-][N+](=O)C1=NC=CN1 YZEUHQHUFTYLPH-UHFFFAOYSA-N 0.000 description 1
- LBKPHBYDOWPFMZ-UHFFFAOYSA-N 3'(S),4'(R)-biangeloyloxys-3',4'-dihydroxanthyletin Natural products O1C(=O)C=CC2=C1C=C1OC(C)(C)C(OC(=O)C(C)=CC)C(OC(=O)C(C)=CC)C1=C2 LBKPHBYDOWPFMZ-UHFFFAOYSA-N 0.000 description 1
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
- PYSICVOJSJMFKP-UHFFFAOYSA-N 3,5-dibromo-2-chloropyridine Chemical compound ClC1=NC=C(Br)C=C1Br PYSICVOJSJMFKP-UHFFFAOYSA-N 0.000 description 1
- WUIABRMSWOKTOF-OYALTWQYSA-N 3-[[2-[2-[2-[[(2s,3r)-2-[[(2s,3s,4r)-4-[[(2s,3r)-2-[[6-amino-2-[(1s)-3-amino-1-[[(2s)-2,3-diamino-3-oxopropyl]amino]-3-oxopropyl]-5-methylpyrimidine-4-carbonyl]amino]-3-[(2r,3s,4s,5s,6s)-3-[(2r,3s,4s,5r,6r)-4-carbamoyloxy-3,5-dihydroxy-6-(hydroxymethyl)ox Chemical compound OS([O-])(=O)=O.N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1NC=NC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C WUIABRMSWOKTOF-OYALTWQYSA-N 0.000 description 1
- OROGUZVNAFJPHA-UHFFFAOYSA-N 3-hydroxy-2,4-dimethyl-2H-thiophen-5-one Chemical compound CC1SC(=O)C(C)=C1O OROGUZVNAFJPHA-UHFFFAOYSA-N 0.000 description 1
- PIAMNHTVFPWVHG-UHFFFAOYSA-N 4-(4-chlorophenyl)-5-methyl-1h-imidazole;hydrochloride Chemical compound Cl.N1C=NC(C=2C=CC(Cl)=CC=2)=C1C PIAMNHTVFPWVHG-UHFFFAOYSA-N 0.000 description 1
- INDZCVYWKNWKIQ-UHFFFAOYSA-N 4-(fluoren-9-ylidenemethyl)benzenecarboximidamide;hydrochloride Chemical compound Cl.C1=CC(C(=N)N)=CC=C1C=C1C2=CC=CC=C2C2=CC=CC=C21 INDZCVYWKNWKIQ-UHFFFAOYSA-N 0.000 description 1
- CXSJGNHRBWJXEA-UHFFFAOYSA-N 5,12-dihydrophthalazino[3,2-b]phthalazine-7,14-dione Chemical compound C1C2=CC=CC=C2C(=O)N2N1C(=O)C1=CC=CC=C1C2 CXSJGNHRBWJXEA-UHFFFAOYSA-N 0.000 description 1
- PXLPCZJACKUXGP-UHFFFAOYSA-N 5-(3,4-dichlorophenyl)-6-ethylpyrimidine-2,4-diamine Chemical compound CCC1=NC(N)=NC(N)=C1C1=CC=C(Cl)C(Cl)=C1 PXLPCZJACKUXGP-UHFFFAOYSA-N 0.000 description 1
- XAUDJQYHKZQPEU-KVQBGUIXSA-N 5-aza-2'-deoxycytidine Chemical compound O=C1N=C(N)N=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 XAUDJQYHKZQPEU-KVQBGUIXSA-N 0.000 description 1
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 description 1
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 description 1
- OTSZCHORPMQCBZ-UHFFFAOYSA-N 6-[(3-chlorophenyl)-imidazol-1-ylmethyl]-1h-benzimidazole;hydron;chloride Chemical compound Cl.ClC1=CC=CC(C(C=2C=C3NC=NC3=CC=2)N2C=NC=C2)=C1 OTSZCHORPMQCBZ-UHFFFAOYSA-N 0.000 description 1
- KXBCLNRMQPRVTP-UHFFFAOYSA-N 6-amino-1,5-dihydroimidazo[4,5-c]pyridin-4-one Chemical compound O=C1NC(N)=CC2=C1N=CN2 KXBCLNRMQPRVTP-UHFFFAOYSA-N 0.000 description 1
- ZNTIXVYOBQDFFV-UHFFFAOYSA-N 6-amino-1,5-dihydroimidazo[4,5-c]pyridin-4-one;methanesulfonic acid Chemical compound CS(O)(=O)=O.O=C1NC(N)=CC2=C1N=CN2 ZNTIXVYOBQDFFV-UHFFFAOYSA-N 0.000 description 1
- OAIZNWQBWDHNIH-UHFFFAOYSA-N 6-chloro-4-phenyl-1-(2,2,2-trifluoroethyl)quinazolin-2-one Chemical compound N=1C(=O)N(CC(F)(F)F)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 OAIZNWQBWDHNIH-UHFFFAOYSA-N 0.000 description 1
- QGHPNWHSLQGRMR-UHFFFAOYSA-N 6h-pyrido[4,3-b]carbazole-1-carboxamide Chemical compound N1C2=CC=CC=C2C2=C1C=C1C=CN=C(C(=O)N)C1=C2 QGHPNWHSLQGRMR-UHFFFAOYSA-N 0.000 description 1
- KABRXLINDSPGDF-UHFFFAOYSA-N 7-bromoisoquinoline Chemical compound C1=CN=CC2=CC(Br)=CC=C21 KABRXLINDSPGDF-UHFFFAOYSA-N 0.000 description 1
- HCKFPALGXKOOBK-NRYMJLQJSA-N 7332-27-6 Chemical compound C1([C@]2(O[C@]3([C@@]4(C)C[C@H](O)[C@]5(F)[C@@]6(C)C=CC(=O)C=C6CC[C@H]5[C@@H]4C[C@H]3O2)C(=O)CO)C)=CC=CC=C1 HCKFPALGXKOOBK-NRYMJLQJSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 208000032671 Allergic granulomatous angiitis Diseases 0.000 description 1
- 206010058285 Allergy to arthropod bite Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 240000008025 Alternanthera ficoidea Species 0.000 description 1
- 201000003076 Angiosarcoma Diseases 0.000 description 1
- 102000015427 Angiotensins Human genes 0.000 description 1
- 108010064733 Angiotensins Proteins 0.000 description 1
- 208000003343 Antiphospholipid Syndrome Diseases 0.000 description 1
- 101100214637 Arabidopsis thaliana PGL4 gene Proteins 0.000 description 1
- 102000015790 Asparaginase Human genes 0.000 description 1
- 108010024976 Asparaginase Proteins 0.000 description 1
- 108700032558 Aspergillus restrictus MITF Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 description 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- HNNIWKQLJSNAEQ-UHFFFAOYSA-N Benzydamine hydrochloride Chemical compound Cl.C12=CC=CC=C2C(OCCCN(C)C)=NN1CC1=CC=CC=C1 HNNIWKQLJSNAEQ-UHFFFAOYSA-N 0.000 description 1
- 206010004593 Bile duct cancer Diseases 0.000 description 1
- 206010004659 Biliary cirrhosis Diseases 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 108010004032 Bromelains Proteins 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 description 1
- 206010006811 Bursitis Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- FVLVBPDQNARYJU-XAHDHGMMSA-N C[C@H]1CCC(CC1)NC(=O)N(CCCl)N=O Chemical compound C[C@H]1CCC(CC1)NC(=O)N(CCCl)N=O FVLVBPDQNARYJU-XAHDHGMMSA-N 0.000 description 1
- 101100114367 Caenorhabditis elegans col-91 gene Proteins 0.000 description 1
- 101100297347 Caenorhabditis elegans pgl-3 gene Proteins 0.000 description 1
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 208000005243 Chondrosarcoma Diseases 0.000 description 1
- 201000009047 Chordoma Diseases 0.000 description 1
- 208000006332 Choriocarcinoma Diseases 0.000 description 1
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
- 208000006344 Churg-Strauss Syndrome Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- KWHNXZAUGQZEDI-UHFFFAOYSA-N Cl.[Ge] Chemical compound Cl.[Ge] KWHNXZAUGQZEDI-UHFFFAOYSA-N 0.000 description 1
- OZKVWEFAUVQIND-UHFFFAOYSA-N ClC1=C2C(C(=C(C(C2=CC=C1)=O)O)Cl)=O Chemical compound ClC1=C2C(C(=C(C(C2=CC=C1)=O)O)Cl)=O OZKVWEFAUVQIND-UHFFFAOYSA-N 0.000 description 1
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 1
- 208000027932 Collagen disease Diseases 0.000 description 1
- YXKFATPOEMHNMJ-KJEYTGHBSA-N Cormethasone acetate Chemical compound C1C(F)(F)C2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)COC(C)=O)(O)[C@@]1(C)C[C@@H]2O YXKFATPOEMHNMJ-KJEYTGHBSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 208000009798 Craniopharyngioma Diseases 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- SPKNARKFCOPTSY-UHFFFAOYSA-N D-asperlin Natural products CC1OC1C1C(OC(C)=O)C=CC(=O)O1 SPKNARKFCOPTSY-UHFFFAOYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- 108010013198 Daptomycin Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- 239000005507 Diflufenican Substances 0.000 description 1
- MWWSFMDVAYGXBV-RUELKSSGSA-N Doxorubicin hydrochloride Chemical compound Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 MWWSFMDVAYGXBV-RUELKSSGSA-N 0.000 description 1
- 206010013700 Drug hypersensitivity Diseases 0.000 description 1
- 208000001708 Dupuytren contracture Diseases 0.000 description 1
- 101150114117 EGR1 gene Proteins 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 201000009051 Embryonal Carcinoma Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- NBEALWAVEGMZQY-UHFFFAOYSA-N Enpromate Chemical compound C=1C=CC=CC=1C(C#C)(C=1C=CC=CC=1)OC(=O)NC1CCCCC1 NBEALWAVEGMZQY-UHFFFAOYSA-N 0.000 description 1
- 208000018428 Eosinophilic granulomatosis with polyangiitis Diseases 0.000 description 1
- 206010014967 Ependymoma Diseases 0.000 description 1
- 201000011275 Epicondylitis Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- 201000008808 Fibrosarcoma Diseases 0.000 description 1
- 108090000331 Firefly luciferases Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 208000004262 Food Hypersensitivity Diseases 0.000 description 1
- 206010016946 Food allergy Diseases 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 206010017918 Gastroenteritis viral Diseases 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 206010018378 Glomerulonephritis rapidly progressive Diseases 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 208000035895 Guillain-Barré syndrome Diseases 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- MUQNGPZZQDCDFT-JNQJZLCISA-N Halcinonide Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CCl)[C@@]1(C)C[C@@H]2O MUQNGPZZQDCDFT-JNQJZLCISA-N 0.000 description 1
- YCISZOVUHXIOFY-HKXOFBAYSA-N Halopredone acetate Chemical compound C1([C@H](F)C2)=CC(=O)C(Br)=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2CC[C@](OC(C)=O)(C(=O)COC(=O)C)[C@@]2(C)C[C@@H]1O YCISZOVUHXIOFY-HKXOFBAYSA-N 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 208000001204 Hashimoto Disease Diseases 0.000 description 1
- 208000001258 Hemangiosarcoma Diseases 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
- ACEWLPOYLGNNHV-UHFFFAOYSA-N Ibuprofen piconol Chemical compound C1=CC(CC(C)C)=CC=C1C(C)C(=O)OCC1=CC=CC=N1 ACEWLPOYLGNNHV-UHFFFAOYSA-N 0.000 description 1
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 108010078049 Interferon alpha-2 Proteins 0.000 description 1
- 108010079944 Interferon-alpha2b Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 description 1
- 108700021006 Interleukin-1 receptor antagonist Proteins 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 208000017119 Labyrinth disease Diseases 0.000 description 1
- 208000007811 Latex Hypersensitivity Diseases 0.000 description 1
- 208000018142 Leiomyosarcoma Diseases 0.000 description 1
- 239000012097 Lipofectamine 2000 Substances 0.000 description 1
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 208000028018 Lymphocytic leukaemia Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- SBDNJUWAMKYJOX-UHFFFAOYSA-N Meclofenamic Acid Chemical compound CC1=CC=C(Cl)C(NC=2C(=CC=CC=2)C(O)=O)=C1Cl SBDNJUWAMKYJOX-UHFFFAOYSA-N 0.000 description 1
- HUXCOHMTWUSXGY-GAPIFECDSA-N Meclorisone dibutyrate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)COC(=O)CCC)(OC(=O)CCC)[C@@]1(C)C[C@@H]2Cl HUXCOHMTWUSXGY-GAPIFECDSA-N 0.000 description 1
- 208000007054 Medullary Carcinoma Diseases 0.000 description 1
- 208000000172 Medulloblastoma Diseases 0.000 description 1
- 208000024556 Mendelian disease Diseases 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 206010027406 Mesothelioma Diseases 0.000 description 1
- 235000017784 Mespilus germanica Nutrition 0.000 description 1
- 206010049567 Miller Fisher syndrome Diseases 0.000 description 1
- 244000182216 Mimusops elengi Species 0.000 description 1
- 235000000560 Mimusops elengi Nutrition 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- HRHKSTOGXBBQCB-UHFFFAOYSA-N Mitomycin E Natural products O=C1C(N)=C(C)C(=O)C2=C1C(COC(N)=O)C1(OC)C3N(C)C3CN12 HRHKSTOGXBBQCB-UHFFFAOYSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101100444898 Mus musculus Egr1 gene Proteins 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- BLXXJMDCKKHMKV-UHFFFAOYSA-N Nabumetone Chemical compound C1=C(CCC(C)=O)C=CC2=CC(OC)=CC=C21 BLXXJMDCKKHMKV-UHFFFAOYSA-N 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- KYRVNWMVYQXFEU-UHFFFAOYSA-N Nocodazole Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1C(=O)C1=CC=CS1 KYRVNWMVYQXFEU-UHFFFAOYSA-N 0.000 description 1
- UMDBGTRUNWFBPE-UHFFFAOYSA-N O.Cl.Cl.CNCCNc1ccc2c3c(nn2CCNCCO)c4c(O)ccc(O)c4C(=O)c13 Chemical compound O.Cl.Cl.CNCCNc1ccc2c3c(nn2CCNCCO)c4c(O)ccc(O)c4C(=O)c13 UMDBGTRUNWFBPE-UHFFFAOYSA-N 0.000 description 1
- FOQXBQHXOQYZSM-UHFFFAOYSA-N OC1=NC2=CC=CC=C2C=C1.[P] Chemical compound OC1=NC2=CC=CC=C2C=C1.[P] FOQXBQHXOQYZSM-UHFFFAOYSA-N 0.000 description 1
- 201000010133 Oligodendroglioma Diseases 0.000 description 1
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 235000019482 Palm oil Nutrition 0.000 description 1
- 208000016222 Pancreatic disease Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 241000254064 Photinus pyralis Species 0.000 description 1
- 208000007641 Pinealoma Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 208000034943 Primary Sjögren syndrome Diseases 0.000 description 1
- 208000024777 Prion disease Diseases 0.000 description 1
- 208000033826 Promyelocytic Acute Leukemia Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- XESARGFCSKSFID-UHFFFAOYSA-N Pyrazofurin Natural products OC1=C(C(=O)N)NN=C1C1C(O)C(O)C(CO)O1 XESARGFCSKSFID-UHFFFAOYSA-N 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 238000010802 RNA extraction kit Methods 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 206010039227 Rotator cuff syndrome Diseases 0.000 description 1
- 206010039251 Rubber sensitivity Diseases 0.000 description 1
- 101150101256 SAMD9 gene Proteins 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 201000010208 Seminoma Diseases 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 201000002661 Spondylitis Diseases 0.000 description 1
- 102000009329 Sterile alpha motif domains Human genes 0.000 description 1
- 108050000172 Sterile alpha motif domains Proteins 0.000 description 1
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 208000001106 Takayasu Arteritis Diseases 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- 108010017842 Telomerase Proteins 0.000 description 1
- 208000000491 Tendinopathy Diseases 0.000 description 1
- 206010043255 Tendonitis Diseases 0.000 description 1
- 208000002240 Tennis Elbow Diseases 0.000 description 1
- 208000004760 Tenosynovitis Diseases 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testosterone Natural products O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- GNVMUORYQLCPJZ-UHFFFAOYSA-M Thiocarbamate Chemical compound NC([S-])=O GNVMUORYQLCPJZ-UHFFFAOYSA-M 0.000 description 1
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 1
- IWEQQRMGNVVKQW-OQKDUQJOSA-N Toremifene citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 IWEQQRMGNVVKQW-OQKDUQJOSA-N 0.000 description 1
- 241000159241 Toxicodendron Species 0.000 description 1
- 241000159243 Toxicodendron radicans Species 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 206010044654 Trigger finger Diseases 0.000 description 1
- 108010050144 Triptorelin Pamoate Proteins 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 206010053614 Type III immune complex mediated reaction Diseases 0.000 description 1
- VGQOVCHZGQWAOI-UHFFFAOYSA-N UNPD55612 Natural products N1C(O)C2CC(C=CC(N)=O)=CN2C(=O)C2=CC=C(C)C(O)=C12 VGQOVCHZGQWAOI-UHFFFAOYSA-N 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 235000007837 Vangueria infausta Nutrition 0.000 description 1
- 208000014070 Vestibular schwannoma Diseases 0.000 description 1
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 208000008383 Wilms tumor Diseases 0.000 description 1
- LBKPHBYDOWPFMZ-LEWJYISDSA-N Xanthralin Natural products CC=C(C)C(=O)O[C@@H]1[C@@H](OC(=O)C(=CC)C)C(C)(C)Oc2cc3OC(=O)C=Cc3cc12 LBKPHBYDOWPFMZ-LEWJYISDSA-N 0.000 description 1
- VUPBDWQPEOWRQP-RTUCOMKBSA-N [(2R,3S,4S,5R,6R)-2-[(2R,3S,4S,5S,6S)-2-[(1S,2S)-3-[[(2R,3S)-5-[[(2S,3R)-1-[[2-[4-[4-[[4-amino-6-[3-(4-aminobutylamino)propylamino]-6-oxohexyl]carbamoyl]-1,3-thiazol-2-yl]-1,3-thiazol-2-yl]-1-[(2S,3R,4R,5S,6S)-5-amino-3,4-dihydroxy-6-methyloxan-2-yl]oxy-2-hydroxyethyl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-hydroxy-5-oxopentan-2-yl]amino]-2-[[6-amino-2-[(1S)-3-amino-1-[[(2S)-2,3-diamino-3-oxopropyl]amino]-3-oxopropyl]-5-methylpyrimidine-4-carbonyl]amino]-1-(1H-imidazol-5-yl)-3-oxopropoxy]-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl] carbamate Chemical compound C[C@@H](O)[C@H](NC(=O)C[C@H](O)[C@@H](C)NC(=O)[C@@H](NC(=O)c1nc(nc(N)c1C)[C@H](CC(N)=O)NC[C@H](N)C(N)=O)[C@H](O[C@@H]1O[C@@H](CO)[C@@H](O)[C@H](O)[C@@H]1O[C@H]1O[C@H](CO)[C@@H](O)[C@H](OC(N)=O)[C@@H]1O)c1cnc[nH]1)C(=O)NC(O[C@@H]1O[C@@H](C)[C@@H](N)[C@@H](O)[C@H]1O)C(O)c1nc(cs1)-c1nc(cs1)C(=O)NCCCC(N)CC(=O)NCCCNCCCCN VUPBDWQPEOWRQP-RTUCOMKBSA-N 0.000 description 1
- SPKNARKFCOPTSY-XWPZMVOTSA-N [(2r,3s)-2-[(2s,3r)-3-methyloxiran-2-yl]-6-oxo-2,3-dihydropyran-3-yl] acetate Chemical compound C[C@H]1O[C@@H]1[C@H]1[C@@H](OC(C)=O)C=CC(=O)O1 SPKNARKFCOPTSY-XWPZMVOTSA-N 0.000 description 1
- LBKPHBYDOWPFMZ-ACVPTOMQSA-N [(3r,4r)-2,2-dimethyl-3-[(e)-2-methylbut-2-enoyl]oxy-8-oxo-3,4-dihydropyrano[3,2-g]chromen-4-yl] (z)-2-methylbut-2-enoate Chemical compound O1C(=O)C=CC2=C1C=C1OC(C)(C)[C@H](OC(=O)C(\C)=C\C)[C@H](OC(=O)C(\C)=C/C)C1=C2 LBKPHBYDOWPFMZ-ACVPTOMQSA-N 0.000 description 1
- KMLCRELJHYKIIL-UHFFFAOYSA-N [1-(azanidylmethyl)cyclohexyl]methylazanide;platinum(2+);sulfuric acid Chemical compound [Pt+2].OS(O)(=O)=O.[NH-]CC1(C[NH-])CCCCC1 KMLCRELJHYKIIL-UHFFFAOYSA-N 0.000 description 1
- DERCOWNWEPPIHD-UHFFFAOYSA-N [17-(2-chloroacetyl)-9-fluoro-11-hydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl] butanoate Chemical compound C1CC2=CC(=O)C=CC2(C)C2(F)C1C1CC(C)C(C(=O)CCl)(OC(=O)CCC)C1(C)CC2O DERCOWNWEPPIHD-UHFFFAOYSA-N 0.000 description 1
- ODEDPKNSRBCSDO-UHFFFAOYSA-N [2-(hexadecylsulfanylmethyl)-3-methoxypropyl] 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCCSCC(COC)COP([O-])(=O)OCC[N+](C)(C)C ODEDPKNSRBCSDO-UHFFFAOYSA-N 0.000 description 1
- JURAJLFHWXNPHG-UHFFFAOYSA-N [acetyl(methylcarbamoyl)amino] n-methylcarbamate Chemical compound CNC(=O)ON(C(C)=O)C(=O)NC JURAJLFHWXNPHG-UHFFFAOYSA-N 0.000 description 1
- 238000010317 ablation therapy Methods 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- RUGAHXUZHWYHNG-NLGNTGLNSA-N acetic acid;(4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-n-[(2s,3r)-1-amino-3-hydroxy-1-oxobutan-2-yl]-19-[[(2r)-2-amino-3-naphthalen-2-ylpropanoyl]amino]-16-[(4-hydroxyphenyl)methyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-7-propan-2-yl-1,2-dithia-5, Chemical compound CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O.C([C@H]1C(=O)N[C@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](N)CC=1C=C2C=CC=CC2=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(N)=O)=O)C(C)C)C1=CC=C(O)C=C1.C([C@H]1C(=O)N[C@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](N)CC=1C=C2C=CC=CC2=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(N)=O)=O)C(C)C)C1=CC=C(O)C=C1 RUGAHXUZHWYHNG-NLGNTGLNSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- QAWIHIJWNYOLBE-OKKQSCSOSA-N acivicin Chemical compound OC(=O)[C@@H](N)[C@@H]1CC(Cl)=NO1 QAWIHIJWNYOLBE-OKKQSCSOSA-N 0.000 description 1
- 229950008427 acivicin Drugs 0.000 description 1
- USZYSDMBJDPRIF-SVEJIMAYSA-N aclacinomycin A Chemical compound O([C@H]1[C@@H](O)C[C@@H](O[C@H]1C)O[C@H]1[C@H](C[C@@H](O[C@H]1C)O[C@H]1C[C@]([C@@H](C2=CC=3C(=O)C4=CC=CC(O)=C4C(=O)C=3C(O)=C21)C(=O)OC)(O)CC)N(C)C)[C@H]1CCC(=O)[C@H](C)O1 USZYSDMBJDPRIF-SVEJIMAYSA-N 0.000 description 1
- 229960004176 aclarubicin Drugs 0.000 description 1
- 208000004064 acoustic neuroma Diseases 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 238000011374 additional therapy Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 229940040563 agaric acid Drugs 0.000 description 1
- 229960005142 alclofenac Drugs 0.000 description 1
- ARHWPKZXBHOEEE-UHFFFAOYSA-N alclofenac Chemical compound OC(=O)CC1=CC=C(OCC=C)C(Cl)=C1 ARHWPKZXBHOEEE-UHFFFAOYSA-N 0.000 description 1
- LSWBQIAZNGURQV-WTBIUSKOSA-N algestone acetonide Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)C)[C@@]1(C)CC2 LSWBQIAZNGURQV-WTBIUSKOSA-N 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 102000004139 alpha-Amylases Human genes 0.000 description 1
- 108090000637 alpha-Amylases Proteins 0.000 description 1
- 229940024171 alpha-amylase Drugs 0.000 description 1
- 229960000473 altretamine Drugs 0.000 description 1
- 229950004821 ambomycin Drugs 0.000 description 1
- NSZFBGIRFCHKOE-LFZVSNMSSA-N amcinafal Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(CC)(CC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O NSZFBGIRFCHKOE-LFZVSNMSSA-N 0.000 description 1
- 229950004850 amcinafal Drugs 0.000 description 1
- 229950003408 amcinafide Drugs 0.000 description 1
- 229960004104 amiloride hydrochloride Drugs 0.000 description 1
- LTKVFMLMEYCWMK-UHFFFAOYSA-N amiloride hydrochloride dihydrate Chemical compound [H+].O.O.[Cl-].NC(=N)NC(=O)C1=NC(Cl)=C(N)N=C1N LTKVFMLMEYCWMK-UHFFFAOYSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229960003437 aminoglutethimide Drugs 0.000 description 1
- ROBVIMPUHSLWNV-UHFFFAOYSA-N aminoglutethimide Chemical compound C=1C=C(N)C=CC=1C1(CC)CCC(=O)NC1=O ROBVIMPUHSLWNV-UHFFFAOYSA-N 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 229960001220 amsacrine Drugs 0.000 description 1
- XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 description 1
- 229960004238 anakinra Drugs 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229960002932 anastrozole Drugs 0.000 description 1
- YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- VGQOVCHZGQWAOI-HYUHUPJXSA-N anthramycin Chemical compound N1[C@@H](O)[C@@H]2CC(\C=C\C(N)=O)=CN2C(=O)C2=CC=C(C)C(O)=C12 VGQOVCHZGQWAOI-HYUHUPJXSA-N 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 229940044684 anti-microtubule agent Drugs 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000013059 antihormonal agent Substances 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 208000026764 autoimmune bullous skin disease Diseases 0.000 description 1
- 201000011385 autoimmune polyendocrine syndrome Diseases 0.000 description 1
- 230000006472 autoimmune response Effects 0.000 description 1
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 1
- 229960002756 azacitidine Drugs 0.000 description 1
- 229950002182 azatepa Drugs 0.000 description 1
- 229950004295 azotomycin Drugs 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 229960000560 balsalazide disodium Drugs 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229950005567 benzodepa Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical group OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 229960001689 benzydamine hydrochloride Drugs 0.000 description 1
- VFIUCBTYGKMLCM-UHFFFAOYSA-N benzyl n-[bis(aziridin-1-yl)phosphoryl]carbamate Chemical compound C=1C=CC=CC=1COC(=O)NP(=O)(N1CC1)N1CC1 VFIUCBTYGKMLCM-UHFFFAOYSA-N 0.000 description 1
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 229960000997 bicalutamide Drugs 0.000 description 1
- 201000007180 bile duct carcinoma Diseases 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000012867 bioactive agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000008236 biological pathway Effects 0.000 description 1
- UIDLJTHRRPMIQP-UHFFFAOYSA-L bis[2-[4-(2-methylpropyl)phenyl]propanoyloxy]aluminum;hydrate Chemical compound O.C1=CC(CC(C)C)=CC=C1C(C)C(=O)O[Al]OC(=O)C(C)C1=CC=C(CC(C)C)C=C1 UIDLJTHRRPMIQP-UHFFFAOYSA-L 0.000 description 1
- 229950008548 bisantrene Drugs 0.000 description 1
- 201000000053 blastoma Diseases 0.000 description 1
- 229960004395 bleomycin sulfate Drugs 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 235000019835 bromelain Nutrition 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229960004436 budesonide Drugs 0.000 description 1
- 208000019748 bullous skin disease Diseases 0.000 description 1
- 108700002839 cactinomycin Proteins 0.000 description 1
- 229950009908 cactinomycin Drugs 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- IVFYLRMMHVYGJH-PVPPCFLZSA-N calusterone Chemical compound C1C[C@]2(C)[C@](O)(C)CC[C@H]2[C@@H]2[C@@H](C)CC3=CC(=O)CC[C@]3(C)[C@H]21 IVFYLRMMHVYGJH-PVPPCFLZSA-N 0.000 description 1
- 229950009823 calusterone Drugs 0.000 description 1
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
- 229940127093 camptothecin Drugs 0.000 description 1
- 229950009338 caracemide Drugs 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 1
- DKVNPHBNOWQYFE-UHFFFAOYSA-N carbamodithioic acid Chemical group NC(S)=S DKVNPHBNOWQYFE-UHFFFAOYSA-N 0.000 description 1
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229960004424 carbon dioxide Drugs 0.000 description 1
- 125000005587 carbonate group Chemical group 0.000 description 1
- YAYRGNWWLMLWJE-UHFFFAOYSA-L carboplatin Chemical compound O=C1O[Pt](N)(N)OC(=O)C11CCC1 YAYRGNWWLMLWJE-UHFFFAOYSA-L 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- XREUEWVEMYWFFA-CSKJXFQVSA-N carminomycin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XREUEWVEMYWFFA-CSKJXFQVSA-N 0.000 description 1
- 229960005243 carmustine Drugs 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 208000003295 carpal tunnel syndrome Diseases 0.000 description 1
- IVUMCTKHWDRRMH-UHFFFAOYSA-N carprofen Chemical compound C1=CC(Cl)=C[C]2C3=CC=C(C(C(O)=O)C)C=C3N=C21 IVUMCTKHWDRRMH-UHFFFAOYSA-N 0.000 description 1
- 229960003184 carprofen Drugs 0.000 description 1
- 229950001725 carubicin Drugs 0.000 description 1
- BBZDXMBRAFTCAA-AREMUKBSSA-N carzelesin Chemical compound C1=2NC=C(C)C=2C([C@H](CCl)CN2C(=O)C=3NC4=CC=C(C=C4C=3)NC(=O)C3=CC4=CC=C(C=C4O3)N(CC)CC)=C2C=C1OC(=O)NC1=CC=CC=C1 BBZDXMBRAFTCAA-AREMUKBSSA-N 0.000 description 1
- 229950007509 carzelesin Drugs 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 239000012578 cell culture reagent Substances 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- CKMOQBVBEGCJGW-UHFFFAOYSA-L chembl1200760 Chemical compound [Na+].[Na+].C1=C(C([O-])=O)C(O)=CC=C1N=NC1=CC=C(C(=O)NCCC([O-])=O)C=C1 CKMOQBVBEGCJGW-UHFFFAOYSA-L 0.000 description 1
- OWSKEUBOCMEJMI-KPXOXKRLSA-N chembl2105946 Chemical compound [N-]=[N+]=CC(=O)CC[C@H](NC(=O)[C@@H](N)C)C(=O)N[C@H](CCC(=O)C=[N+]=[N-])C(O)=O OWSKEUBOCMEJMI-KPXOXKRLSA-N 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 229960004630 chlorambucil Drugs 0.000 description 1
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
- SOYKEARSMXGVTM-UHFFFAOYSA-N chlorphenamine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 SOYKEARSMXGVTM-UHFFFAOYSA-N 0.000 description 1
- 229960003291 chlorphenamine Drugs 0.000 description 1
- TZFWDZFKRBELIQ-UHFFFAOYSA-N chlorzoxazone Chemical compound ClC1=CC=C2OC(O)=NC2=C1 TZFWDZFKRBELIQ-UHFFFAOYSA-N 0.000 description 1
- 229960003633 chlorzoxazone Drugs 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- GPUVGQIASQNZET-CCEZHUSRSA-N cinnoxicam Chemical compound C=1C=CC=CC=1/C=C/C(=O)OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 GPUVGQIASQNZET-CCEZHUSRSA-N 0.000 description 1
- 229950011359 cirolemycin Drugs 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 229960002436 cladribine Drugs 0.000 description 1
- 229950005384 cliprofen Drugs 0.000 description 1
- 229960004703 clobetasol propionate Drugs 0.000 description 1
- CBGUOGMQLZIXBE-XGQKBEPLSA-N clobetasol propionate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CCl)(OC(=O)CC)[C@@]1(C)C[C@@H]2O CBGUOGMQLZIXBE-XGQKBEPLSA-N 0.000 description 1
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 1
- 229960003009 clopidogrel Drugs 0.000 description 1
- SJCRQMUYEQHNTC-UHFFFAOYSA-N clopirac Chemical compound CC1=CC(CC(O)=O)=C(C)N1C1=CC=C(Cl)C=C1 SJCRQMUYEQHNTC-UHFFFAOYSA-N 0.000 description 1
- 229950009185 clopirac Drugs 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 201000005637 crescentic glomerulonephritis Diseases 0.000 description 1
- DMSZORWOGDLWGN-UHFFFAOYSA-N ctk1a3526 Chemical compound NP(N)(N)=O DMSZORWOGDLWGN-UHFFFAOYSA-N 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 208000002445 cystadenocarcinoma Diseases 0.000 description 1
- 229960000684 cytarabine Drugs 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- YCWXIQRLONXJLF-PFFGJIDWSA-N d06307 Chemical compound OS(O)(=O)=O.C([C@]1([C@@H]2O1)CC)N(CCC=1C3=CC=CC=C3NC=11)C[C@H]2C[C@]1(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC.C([C@]1([C@@H]2O1)CC)N(CCC=1C3=CC=CC=C3NC=11)C[C@H]2C[C@]1(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC YCWXIQRLONXJLF-PFFGJIDWSA-N 0.000 description 1
- 229960003901 dacarbazine Drugs 0.000 description 1
- DOAKLVKFURWEDJ-QCMAZARJSA-N daptomycin Chemical compound C([C@H]1C(=O)O[C@H](C)[C@@H](C(NCC(=O)N[C@@H](CCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@H](CO)C(=O)N[C@H](C(=O)N1)[C@H](C)CC(O)=O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](CC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CCCCCCCCC)C(=O)C1=CC=CC=C1N DOAKLVKFURWEDJ-QCMAZARJSA-N 0.000 description 1
- 229960005484 daptomycin Drugs 0.000 description 1
- 229960003109 daunorubicin hydrochloride Drugs 0.000 description 1
- 229960003603 decitabine Drugs 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- FBHSPRKOSMHSIF-GRMWVWQJSA-N deflazacort Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(C)=N[C@@]3(C(=O)COC(=O)C)[C@@]1(C)C[C@@H]2O FBHSPRKOSMHSIF-GRMWVWQJSA-N 0.000 description 1
- 229960001145 deflazacort Drugs 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- CFCUWKMKBJTWLW-UHFFFAOYSA-N deoliosyl-3C-alpha-L-digitoxosyl-MTM Natural products CC=1C(O)=C2C(O)=C3C(=O)C(OC4OC(C)C(O)C(OC5OC(C)C(O)C(OC6OC(C)C(O)C(C)(O)C6)C5)C4)C(C(OC)C(=O)C(O)C(C)O)CC3=CC2=CC=1OC(OC(C)C1O)CC1OC1CC(O)C(O)C(C)O1 CFCUWKMKBJTWLW-UHFFFAOYSA-N 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000036576 dermal application Effects 0.000 description 1
- 229960002593 desoximetasone Drugs 0.000 description 1
- VWVSBHGCDBMOOT-IIEHVVJPSA-N desoximetasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@H](C(=O)CO)[C@@]1(C)C[C@@H]2O VWVSBHGCDBMOOT-IIEHVVJPSA-N 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- CIWBQSYVNNPZIQ-PKWREOPISA-N dexamethasone dipropionate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)COC(=O)CC)(OC(=O)CC)[C@@]1(C)C[C@@H]2O CIWBQSYVNNPZIQ-PKWREOPISA-N 0.000 description 1
- 229950000250 dexamethasone dipropionate Drugs 0.000 description 1
- VPOCYEOOFRNHNL-RQDPQJJXSA-J dexormaplatin Chemical compound Cl[Pt](Cl)(Cl)Cl.N[C@@H]1CCCC[C@H]1N VPOCYEOOFRNHNL-RQDPQJJXSA-J 0.000 description 1
- 229950001640 dexormaplatin Drugs 0.000 description 1
- 229950010621 dezaguanine Drugs 0.000 description 1
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 description 1
- WVYXNIXAMZOZFK-UHFFFAOYSA-N diaziquone Chemical compound O=C1C(NC(=O)OCC)=C(N2CC2)C(=O)C(NC(=O)OCC)=C1N1CC1 WVYXNIXAMZOZFK-UHFFFAOYSA-N 0.000 description 1
- 229950002389 diaziquone Drugs 0.000 description 1
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 229940042935 dichlorodifluoromethane Drugs 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
- 229960004515 diclofenac potassium Drugs 0.000 description 1
- KXZOIWWTXOCYKR-UHFFFAOYSA-M diclofenac potassium Chemical compound [K+].[O-]C(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl KXZOIWWTXOCYKR-UHFFFAOYSA-M 0.000 description 1
- 229960001193 diclofenac sodium Drugs 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- WYEHFWKAOXOVJD-UHFFFAOYSA-N diflufenican Chemical compound FC1=CC(F)=CC=C1NC(=O)C1=CC=CN=C1OC1=CC=CC(C(F)(F)F)=C1 WYEHFWKAOXOVJD-UHFFFAOYSA-N 0.000 description 1
- 229950007956 diftalone Drugs 0.000 description 1
- OTKJDMGTUTTYMP-UHFFFAOYSA-N dihydrosphingosine Natural products CCCCCCCCCCCCCCCC(O)C(N)CO OTKJDMGTUTTYMP-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- CZLKTMHQYXYHOO-QTNFYWBSSA-L disodium;(2s)-2-[(2-phosphonatoacetyl)amino]butanedioic acid Chemical compound [Na+].[Na+].OC(=O)C[C@@H](C(O)=O)NC(=O)CP([O-])([O-])=O CZLKTMHQYXYHOO-QTNFYWBSSA-L 0.000 description 1
- SVJSWELRJWVPQD-KJWOGLQMSA-L disodium;(2s)-2-[[4-[2-[(6r)-2-amino-4-oxo-5,6,7,8-tetrahydro-1h-pyrido[2,3-d]pyrimidin-6-yl]ethyl]benzoyl]amino]pentanedioate Chemical compound [Na+].[Na+].C([C@@H]1CC=2C(=O)N=C(NC=2NC1)N)CC1=CC=C(C(=O)N[C@@H](CCC([O-])=O)C([O-])=O)C=C1 SVJSWELRJWVPQD-KJWOGLQMSA-L 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 229960003530 donepezil Drugs 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000002222 downregulating effect Effects 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229960002918 doxorubicin hydrochloride Drugs 0.000 description 1
- GZBONOYGBJSTHF-QLRNAMTQSA-N drocinonide Chemical compound C([C@@H]1CC2)C(=O)CC[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O GZBONOYGBJSTHF-QLRNAMTQSA-N 0.000 description 1
- 229950006082 drocinonide Drugs 0.000 description 1
- 201000005311 drug allergy Diseases 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000010864 dual luciferase reporter gene assay Methods 0.000 description 1
- 229950005133 duazomycin Drugs 0.000 description 1
- 229930192837 duazomycin Natural products 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 210000003027 ear inner Anatomy 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 229960002046 eflornithine hydrochloride Drugs 0.000 description 1
- 201000008184 embryoma Diseases 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 201000002491 encephalomyelitis Diseases 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229950002798 enlimomab Drugs 0.000 description 1
- 229950001022 enpromate Drugs 0.000 description 1
- 230000002327 eosinophilic effect Effects 0.000 description 1
- YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 0.000 description 1
- 229960003265 epirubicin hydrochloride Drugs 0.000 description 1
- 229930013356 epothilone Natural products 0.000 description 1
- 150000003883 epothilone derivatives Chemical class 0.000 description 1
- HCZKYJDFEPMADG-UHFFFAOYSA-N erythro-nordihydroguaiaretic acid Natural products C=1C=C(O)C(O)=CC=1CC(C)C(C)CC1=CC=C(O)C(O)=C1 HCZKYJDFEPMADG-UHFFFAOYSA-N 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 229960001842 estramustine Drugs 0.000 description 1
- FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 description 1
- IIUMCNJTGSMNRO-VVSKJQCTSA-L estramustine sodium phosphate Chemical compound [Na+].[Na+].ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)OP([O-])([O-])=O)[C@@H]4[C@@H]3CCC2=C1 IIUMCNJTGSMNRO-VVSKJQCTSA-L 0.000 description 1
- ULANGSAJTINEBA-UHFFFAOYSA-N ethyl n-(3-benzoylphenyl)-n-(trifluoromethylsulfonyl)carbamate Chemical compound CCOC(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 ULANGSAJTINEBA-UHFFFAOYSA-N 0.000 description 1
- HZQPPNNARUQMJA-IMIWJGOWSA-N ethyl n-[4-[[(2r,4r)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methylsulfanyl]phenyl]carbamate;hydrochloride Chemical compound Cl.C1=CC(NC(=O)OCC)=CC=C1SC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 HZQPPNNARUQMJA-IMIWJGOWSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 229960005293 etodolac Drugs 0.000 description 1
- XFBVBWWRPKNWHW-UHFFFAOYSA-N etodolac Chemical compound C1COC(CC)(CC(O)=O)C2=N[C]3C(CC)=CC=CC3=C21 XFBVBWWRPKNWHW-UHFFFAOYSA-N 0.000 description 1
- 229960001493 etofenamate Drugs 0.000 description 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- LIQODXNTTZAGID-OCBXBXKTSA-N etoposide phosphate Chemical compound COC1=C(OP(O)(O)=O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 LIQODXNTTZAGID-OCBXBXKTSA-N 0.000 description 1
- 229960000752 etoposide phosphate Drugs 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 229960000301 factor viii Drugs 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 229950003579 fenamole Drugs 0.000 description 1
- 229960001395 fenbufen Drugs 0.000 description 1
- ZPAKPRAICRBAOD-UHFFFAOYSA-N fenbufen Chemical compound C1=CC(C(=O)CCC(=O)O)=CC=C1C1=CC=CC=C1 ZPAKPRAICRBAOD-UHFFFAOYSA-N 0.000 description 1
- 229950003537 fenclorac Drugs 0.000 description 1
- HAWWPSYXSLJRBO-UHFFFAOYSA-N fendosal Chemical compound C1=C(O)C(C(=O)O)=CC(N2C(=CC=3C4=CC=CC=C4CCC=32)C=2C=CC=CC=2)=C1 HAWWPSYXSLJRBO-UHFFFAOYSA-N 0.000 description 1
- 229950005416 fendosal Drugs 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 210000003811 finger Anatomy 0.000 description 1
- 229960000961 floxuridine Drugs 0.000 description 1
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 description 1
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 1
- LPEPZBJOKDYZAD-UHFFFAOYSA-N flufenamic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=CC(C(F)(F)F)=C1 LPEPZBJOKDYZAD-UHFFFAOYSA-N 0.000 description 1
- 229960004369 flufenamic acid Drugs 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- OPYFPDBMMYUPME-UHFFFAOYSA-N flumizole Chemical compound C1=CC(OC)=CC=C1C1=C(C=2C=CC(OC)=CC=2)NC(C(F)(F)F)=N1 OPYFPDBMMYUPME-UHFFFAOYSA-N 0.000 description 1
- 229950005288 flumizole Drugs 0.000 description 1
- XWTIDFOGTCVGQB-FHIVUSPVSA-N fluocortin butyl Chemical group C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@@H](C)[C@H](C(=O)C(=O)OCCCC)[C@@]2(C)C[C@@H]1O XWTIDFOGTCVGQB-FHIVUSPVSA-N 0.000 description 1
- 229950008509 fluocortin butyl Drugs 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 229960001629 fluorometholone acetate Drugs 0.000 description 1
- YRFXGQHBPBMFHW-SBTZIJSASA-N fluorometholone acetate Chemical compound C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@]2(F)[C@@H](O)C[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 YRFXGQHBPBMFHW-SBTZIJSASA-N 0.000 description 1
- 150000005699 fluoropyrimidines Chemical class 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 229950007253 fluquazone Drugs 0.000 description 1
- 229960002390 flurbiprofen Drugs 0.000 description 1
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
- 229950005682 flurocitabine Drugs 0.000 description 1
- 229960000289 fluticasone propionate Drugs 0.000 description 1
- WMWTYOKRWGGJOA-CENSZEJFSA-N fluticasone propionate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(OC(=O)CC)[C@@]2(C)C[C@@H]1O WMWTYOKRWGGJOA-CENSZEJFSA-N 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 235000020932 food allergy Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- UXTSQCOOUJTIAC-UHFFFAOYSA-N fosquidone Chemical compound C=1N2CC3=CC=CC=C3C(C)C2=C(C(C2=CC=C3)=O)C=1C(=O)C2=C3OP(O)(=O)OCC1=CC=CC=C1 UXTSQCOOUJTIAC-UHFFFAOYSA-N 0.000 description 1
- 229950005611 fosquidone Drugs 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 230000005021 gait Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- 229960005144 gemcitabine hydrochloride Drugs 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000001434 glomerular Effects 0.000 description 1
- 239000006481 glucose medium Substances 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 210000004209 hair Anatomy 0.000 description 1
- 229960002383 halcinonide Drugs 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 229950004611 halopredone acetate Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 201000002222 hemangioblastoma Diseases 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 102000044060 human SAMD9 Human genes 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- SOCGJDYHNGLZEC-UHFFFAOYSA-N hydron;n-methyl-n-[4-[(7-methyl-3h-imidazo[4,5-f]quinolin-9-yl)amino]phenyl]acetamide;chloride Chemical compound Cl.C1=CC(N(C(C)=O)C)=CC=C1NC1=CC(C)=NC2=CC=C(NC=N3)C3=C12 SOCGJDYHNGLZEC-UHFFFAOYSA-N 0.000 description 1
- MSYBLBLAMDYKKZ-UHFFFAOYSA-N hydron;pyridine-3-carbonyl chloride;chloride Chemical compound Cl.ClC(=O)C1=CC=CN=C1 MSYBLBLAMDYKKZ-UHFFFAOYSA-N 0.000 description 1
- DOUHZFSGSXMPIE-UHFFFAOYSA-N hydroxidooxidosulfur(.) Chemical compound [O]SO DOUHZFSGSXMPIE-UHFFFAOYSA-N 0.000 description 1
- 229960001330 hydroxycarbamide Drugs 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000002727 hyperosmolar Effects 0.000 description 1
- 229950005954 ibuprofen piconol Drugs 0.000 description 1
- 229960001176 idarubicin hydrochloride Drugs 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 208000009326 ileitis Diseases 0.000 description 1
- 229950006905 ilmofosine Drugs 0.000 description 1
- 229950011445 ilonidap Drugs 0.000 description 1
- 210000001822 immobilized cell Anatomy 0.000 description 1
- 230000008004 immune attack Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 229940124452 immunizing agent Drugs 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 229960004260 indomethacin sodium Drugs 0.000 description 1
- 229960004187 indoprofen Drugs 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 208000028774 intestinal disease Diseases 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000000185 intracerebroventricular administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229960000779 irinotecan hydrochloride Drugs 0.000 description 1
- GURKHSYORGJETM-WAQYZQTGSA-N irinotecan hydrochloride (anhydrous) Chemical compound Cl.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 GURKHSYORGJETM-WAQYZQTGSA-N 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- YYUAYBYLJSNDCX-UHFFFAOYSA-N isoxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC=1C=C(C)ON=1 YYUAYBYLJSNDCX-UHFFFAOYSA-N 0.000 description 1
- 229950002252 isoxicam Drugs 0.000 description 1
- 210000005067 joint tissue Anatomy 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 229940099367 lanolin alcohols Drugs 0.000 description 1
- 108010021336 lanreotide Proteins 0.000 description 1
- 229960001739 lanreotide acetate Drugs 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 201000005391 latex allergy Diseases 0.000 description 1
- 229960003881 letrozole Drugs 0.000 description 1
- HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 1
- 229960004338 leuprorelin Drugs 0.000 description 1
- KDQAABAKXDWYSZ-SDCRJXSCSA-N leurosidine sulfate Chemical compound OS(O)(=O)=O.C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 KDQAABAKXDWYSZ-SDCRJXSCSA-N 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 206010024627 liposarcoma Diseases 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 230000007108 local immune response Effects 0.000 description 1
- 229960002247 lomustine Drugs 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- OXROWJKCGCOJDO-JLHYYAGUSA-N lornoxicam Chemical compound O=C1C=2SC(Cl)=CC=2S(=O)(=O)N(C)\C1=C(\O)NC1=CC=CC=N1 OXROWJKCGCOJDO-JLHYYAGUSA-N 0.000 description 1
- 229960002202 lornoxicam Drugs 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 1
- 238000003468 luciferase reporter gene assay Methods 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 208000037829 lymphangioendotheliosarcoma Diseases 0.000 description 1
- 208000012804 lymphangiosarcoma Diseases 0.000 description 1
- 208000003747 lymphoid leukemia Diseases 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- GQVWFGYYMWLERN-UHFFFAOYSA-J magnesium;2-carboxyphenolate;2-hydroxyethyl(trimethyl)azanium;sulfate;tetrahydrate Chemical compound O.O.O.O.[Mg+2].[O-]S([O-])(=O)=O.C[N+](C)(C)CCO.C[N+](C)(C)CCO.OC1=CC=CC=C1C([O-])=O.OC1=CC=CC=C1C([O-])=O GQVWFGYYMWLERN-UHFFFAOYSA-J 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 229960003951 masoprocol Drugs 0.000 description 1
- HCZKYJDFEPMADG-TXEJJXNPSA-N masoprocol Chemical compound C([C@H](C)[C@H](C)CC=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 HCZKYJDFEPMADG-TXEJJXNPSA-N 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- QZIQJVCYUQZDIR-UHFFFAOYSA-N mechlorethamine hydrochloride Chemical compound Cl.ClCCN(C)CCCl QZIQJVCYUQZDIR-UHFFFAOYSA-N 0.000 description 1
- 229960002868 mechlorethamine hydrochloride Drugs 0.000 description 1
- 229960003803 meclofenamic acid Drugs 0.000 description 1
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 1
- HYYBABOKPJLUIN-UHFFFAOYSA-N mefenamic acid Chemical compound CC1=CC=CC(NC=2C(=CC=CC=2)C(O)=O)=C1C HYYBABOKPJLUIN-UHFFFAOYSA-N 0.000 description 1
- 229960003464 mefenamic acid Drugs 0.000 description 1
- 229960004296 megestrol acetate Drugs 0.000 description 1
- RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 1
- 229960003846 melengestrol acetate Drugs 0.000 description 1
- 229960001924 melphalan Drugs 0.000 description 1
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 206010027191 meningioma Diseases 0.000 description 1
- LWYJUZBXGAFFLP-OCNCTQISSA-N menogaril Chemical compound O1[C@@]2(C)[C@H](O)[C@@H](N(C)C)[C@H](O)[C@@H]1OC1=C3C(=O)C(C=C4C[C@@](C)(O)C[C@H](C4=C4O)OC)=C4C(=O)C3=C(O)C=C12 LWYJUZBXGAFFLP-OCNCTQISSA-N 0.000 description 1
- 229950002676 menogaril Drugs 0.000 description 1
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 1
- 229960001428 mercaptopurine Drugs 0.000 description 1
- KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical compound NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 description 1
- 229960004963 mesalazine Drugs 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 208000037819 metastatic cancer Diseases 0.000 description 1
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
- KPQJSSLKKBKWEW-RKDOVGOJSA-N methanesulfonic acid;5-nitro-2-[(2r)-1-[2-[[(2r)-2-(5-nitro-1,3-dioxobenzo[de]isoquinolin-2-yl)propyl]amino]ethylamino]propan-2-yl]benzo[de]isoquinoline-1,3-dione Chemical compound CS(O)(=O)=O.CS(O)(=O)=O.[O-][N+](=O)C1=CC(C(N([C@@H](CNCCNC[C@@H](C)N2C(C=3C=C(C=C4C=CC=C(C=34)C2=O)[N+]([O-])=O)=O)C)C2=O)=O)=C3C2=CC=CC3=C1 KPQJSSLKKBKWEW-RKDOVGOJSA-N 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- BKBBTCORRZMASO-ZOWNYOTGSA-M methotrexate monosodium Chemical compound [Na+].C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C([O-])=O)C=C1 BKBBTCORRZMASO-ZOWNYOTGSA-M 0.000 description 1
- 229960003058 methotrexate sodium Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- HRHKSTOGXBBQCB-VFWICMBZSA-N methylmitomycin Chemical compound O=C1C(N)=C(C)C(=O)C2=C1[C@@H](COC(N)=O)[C@@]1(OC)[C@H]3N(C)[C@H]3CN12 HRHKSTOGXBBQCB-VFWICMBZSA-N 0.000 description 1
- VQJHOPSWBGJHQS-UHFFFAOYSA-N metoprine, methodichlorophen Chemical compound CC1=NC(N)=NC(N)=C1C1=CC=C(Cl)C(Cl)=C1 VQJHOPSWBGJHQS-UHFFFAOYSA-N 0.000 description 1
- QTFKTBRIGWJQQL-UHFFFAOYSA-N meturedepa Chemical compound C1C(C)(C)N1P(=O)(NC(=O)OCC)N1CC1(C)C QTFKTBRIGWJQQL-UHFFFAOYSA-N 0.000 description 1
- 229950009847 meturedepa Drugs 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 210000003632 microfilament Anatomy 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
- DRCJGCOYHLTVNR-ZUIZSQJWSA-N mitindomide Chemical compound C1=C[C@@H]2[C@@H]3[C@H]4C(=O)NC(=O)[C@H]4[C@@H]3[C@H]1[C@@H]1C(=O)NC(=O)[C@H]21 DRCJGCOYHLTVNR-ZUIZSQJWSA-N 0.000 description 1
- 229950001314 mitindomide Drugs 0.000 description 1
- 229950000911 mitogillin Drugs 0.000 description 1
- 108010026677 mitomalcin Proteins 0.000 description 1
- 229950007612 mitomalcin Drugs 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 229950005715 mitosper Drugs 0.000 description 1
- ZAHQPTJLOCWVPG-UHFFFAOYSA-N mitoxantrone dihydrochloride Chemical compound Cl.Cl.O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO ZAHQPTJLOCWVPG-UHFFFAOYSA-N 0.000 description 1
- 229960004169 mitoxantrone hydrochloride Drugs 0.000 description 1
- 201000010225 mixed cell type cancer Diseases 0.000 description 1
- 208000029638 mixed neoplasm Diseases 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
- 229960000951 mycophenolic acid Drugs 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- 208000003786 myxedema Diseases 0.000 description 1
- 208000001611 myxosarcoma Diseases 0.000 description 1
- NKDJNEGDJVXHKM-UHFFFAOYSA-N n,2-dimethyl-4,5,6,7-tetrahydroindazol-3-amine Chemical compound C1CCCC2=NN(C)C(NC)=C21 NKDJNEGDJVXHKM-UHFFFAOYSA-N 0.000 description 1
- HWCORKBTTGTRDY-UHFFFAOYSA-N n-(4-chlorophenyl)-1,3-dioxo-4h-isoquinoline-4-carboxamide Chemical compound C1=CC(Cl)=CC=C1NC(=O)C1C2=CC=CC=C2C(=O)NC1=O HWCORKBTTGTRDY-UHFFFAOYSA-N 0.000 description 1
- NKFHKYQGZDAKMX-PPRKPIOESA-N n-[(e)-1-[(2s,4s)-4-[(2r,4s,5s,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-3,4-dihydro-1h-tetracen-2-yl]ethylideneamino]benzamide;hydrochloride Chemical compound Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(\C)=N\NC(=O)C=1C=CC=CC=1)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 NKFHKYQGZDAKMX-PPRKPIOESA-N 0.000 description 1
- NJSMWLQOCQIOPE-OCHFTUDZSA-N n-[(e)-[10-[(e)-(4,5-dihydro-1h-imidazol-2-ylhydrazinylidene)methyl]anthracen-9-yl]methylideneamino]-4,5-dihydro-1h-imidazol-2-amine Chemical compound N1CCN=C1N\N=C\C(C1=CC=CC=C11)=C(C=CC=C2)C2=C1\C=N\NC1=NCCN1 NJSMWLQOCQIOPE-OCHFTUDZSA-N 0.000 description 1
- BRZOTEHEMOQUOY-UHFFFAOYSA-N n-[bis(aziridin-1-yl)phosphoryl]benzamide Chemical compound C=1C=CC=CC=1C(=O)NP(=O)(N1CC1)N1CC1 BRZOTEHEMOQUOY-UHFFFAOYSA-N 0.000 description 1
- WRINSSLBPNLASA-FOCLMDBBSA-N n-methyl-n-[(e)-(n-methylanilino)diazenyl]aniline Chemical compound C=1C=CC=CC=1N(C)\N=N\N(C)C1=CC=CC=C1 WRINSSLBPNLASA-FOCLMDBBSA-N 0.000 description 1
- 229960004270 nabumetone Drugs 0.000 description 1
- 210000000282 nail Anatomy 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 229960003940 naproxen sodium Drugs 0.000 description 1
- CDBRNDSHEYLDJV-FVGYRXGTSA-M naproxen sodium Chemical compound [Na+].C1=C([C@H](C)C([O-])=O)C=CC2=CC(OC)=CC=C21 CDBRNDSHEYLDJV-FVGYRXGTSA-M 0.000 description 1
- MRWXACSTFXYYMV-FDDDBJFASA-N nebularine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC=C2N=C1 MRWXACSTFXYYMV-FDDDBJFASA-N 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- QZGIWPZCWHMVQL-UIYAJPBUSA-N neocarzinostatin chromophore Chemical compound O1[C@H](C)[C@H](O)[C@H](O)[C@@H](NC)[C@H]1O[C@@H]1C/2=C/C#C[C@H]3O[C@@]3([C@@H]3OC(=O)OC3)C#CC\2=C[C@H]1OC(=O)C1=C(O)C=CC2=C(C)C=C(OC)C=C12 QZGIWPZCWHMVQL-UIYAJPBUSA-N 0.000 description 1
- 208000025189 neoplasm of testis Diseases 0.000 description 1
- 210000005170 neoplastic cell Anatomy 0.000 description 1
- 229950006344 nocodazole Drugs 0.000 description 1
- 102000045246 noggin Human genes 0.000 description 1
- 108700007229 noggin Proteins 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 230000037311 normal skin Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 238000011903 nutritional therapy Methods 0.000 description 1
- 235000014593 oils and fats Nutrition 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 238000000399 optical microscopy Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 229960004534 orgotein Drugs 0.000 description 1
- 108010070915 orgotein Proteins 0.000 description 1
- 229950008017 ormaplatin Drugs 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 208000015124 ovarian disease Diseases 0.000 description 1
- 229960002739 oxaprozin Drugs 0.000 description 1
- OFPXSFXSNFPTHF-UHFFFAOYSA-N oxaprozin Chemical compound O1C(CCC(=O)O)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 OFPXSFXSNFPTHF-UHFFFAOYSA-N 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 229950000370 oxisuran Drugs 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229960000649 oxyphenbutazone Drugs 0.000 description 1
- CNDQSXOVEQXJOE-UHFFFAOYSA-N oxyphenbutazone hydrate Chemical compound O.O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=C(O)C=C1 CNDQSXOVEQXJOE-UHFFFAOYSA-N 0.000 description 1
- 239000002540 palm oil Substances 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 208000004019 papillary adenocarcinoma Diseases 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229950006960 peliomycin Drugs 0.000 description 1
- QOFFJEBXNKRSPX-ZDUSSCGKSA-N pemetrexed Chemical compound C1=N[C]2NC(N)=NC(=O)C2=C1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 QOFFJEBXNKRSPX-ZDUSSCGKSA-N 0.000 description 1
- 229960005079 pemetrexed Drugs 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- VPAWVRUHMJVRHU-VGDKGRGNSA-N perfosfamide Chemical compound OO[C@@H]1CCO[P@@](=O)(N(CCCl)CCCl)N1 VPAWVRUHMJVRHU-VGDKGRGNSA-N 0.000 description 1
- 229950009351 perfosfamide Drugs 0.000 description 1
- 125000000864 peroxy group Chemical group O(O*)* 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229960005487 phenylbutazone sodium Drugs 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 238000002428 photodynamic therapy Methods 0.000 description 1
- 238000001126 phototherapy Methods 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 208000024724 pineal body neoplasm Diseases 0.000 description 1
- 201000004123 pineal gland cancer Diseases 0.000 description 1
- NUKCGLDCWQXYOQ-UHFFFAOYSA-N piposulfan Chemical compound CS(=O)(=O)OCCC(=O)N1CCN(C(=O)CCOS(C)(=O)=O)CC1 NUKCGLDCWQXYOQ-UHFFFAOYSA-N 0.000 description 1
- 229950001100 piposulfan Drugs 0.000 description 1
- XESARGFCSKSFID-FLLFQEBCSA-N pirazofurin Chemical compound OC1=C(C(=O)N)NN=C1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 XESARGFCSKSFID-FLLFQEBCSA-N 0.000 description 1
- 229960003073 pirfenidone Drugs 0.000 description 1
- ISWRGOKTTBVCFA-UHFFFAOYSA-N pirfenidone Chemical compound C1=C(C)C=CC(=O)N1C1=CC=CC=C1 ISWRGOKTTBVCFA-UHFFFAOYSA-N 0.000 description 1
- 229960001369 piroxicam cinnamate Drugs 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229960003171 plicamycin Drugs 0.000 description 1
- JKPDEYAOCSQBSZ-OEUJLIAZSA-N plomestane Chemical compound O=C1CC[C@]2(CC#C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 JKPDEYAOCSQBSZ-OEUJLIAZSA-N 0.000 description 1
- 229950004541 plomestane Drugs 0.000 description 1
- 201000004338 pollen allergy Diseases 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001021 polysulfide Polymers 0.000 description 1
- 229950004406 porfiromycin Drugs 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940116317 potato starch Drugs 0.000 description 1
- FASDKYOPVNHBLU-ZETCQYMHSA-N pramipexole Chemical compound C1[C@@H](NCCC)CCC2=C1SC(N)=N2 FASDKYOPVNHBLU-ZETCQYMHSA-N 0.000 description 1
- 229960003089 pramipexole Drugs 0.000 description 1
- 229950008421 prednazate Drugs 0.000 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- WAAVMZLJRXYRMA-UHFFFAOYSA-N prifelone Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(C(=O)C=2SC=CC=2)=C1 WAAVMZLJRXYRMA-UHFFFAOYSA-N 0.000 description 1
- 229950004465 prifelone Drugs 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 229960002466 proquazone Drugs 0.000 description 1
- JTIGKVIOEQASGT-UHFFFAOYSA-N proquazone Chemical compound N=1C(=O)N(C(C)C)C2=CC(C)=CC=C2C=1C1=CC=CC=C1 JTIGKVIOEQASGT-UHFFFAOYSA-N 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 238000012514 protein characterization Methods 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- FITIWKDOCAUBQD-UHFFFAOYSA-N prothiofos Chemical compound CCCSP(=S)(OCC)OC1=CC=C(Cl)C=C1Cl FITIWKDOCAUBQD-UHFFFAOYSA-N 0.000 description 1
- 239000002212 purine nucleoside Substances 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- MKSVFGKWZLUTTO-FZFAUISWSA-N puromycin dihydrochloride Chemical compound Cl.Cl.C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO MKSVFGKWZLUTTO-FZFAUISWSA-N 0.000 description 1
- SHNUBALDGXWUJI-UHFFFAOYSA-N pyridin-2-ylmethanol Chemical compound OCC1=CC=CC=N1 SHNUBALDGXWUJI-UHFFFAOYSA-N 0.000 description 1
- 239000002718 pyrimidine nucleoside Substances 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 208000017443 reproductive system disease Diseases 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 229940100486 rice starch Drugs 0.000 description 1
- QXKJWHWUDVQATH-UHFFFAOYSA-N rogletimide Chemical compound C=1C=NC=CC=1C1(CC)CCC(=O)NC1=O QXKJWHWUDVQATH-UHFFFAOYSA-N 0.000 description 1
- 229950005230 rogletimide Drugs 0.000 description 1
- 229950001166 romazarit Drugs 0.000 description 1
- 201000005404 rubella Diseases 0.000 description 1
- 229950008902 safingol Drugs 0.000 description 1
- 229950000125 salcolex Drugs 0.000 description 1
- 235000012420 sanguinaria Nutrition 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 201000008407 sebaceous adenocarcinoma Diseases 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 229960003440 semustine Drugs 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000002453 shampoo Substances 0.000 description 1
- 229950009089 simtrazene Drugs 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
- 238000007390 skin biopsy Methods 0.000 description 1
- 231100000245 skin permeability Toxicity 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- QHJLLDJTVQAFAN-UHFFFAOYSA-M sodium meclofenamate monohydrate Chemical compound O.[Na+].CC1=CC=C(Cl)C(NC=2C(=CC=CC=2)C([O-])=O)=C1Cl QHJLLDJTVQAFAN-UHFFFAOYSA-M 0.000 description 1
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 1
- JMHRGKDWGWORNU-UHFFFAOYSA-M sodium;2-[1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetate Chemical compound [Na+].CC1=C(CC([O-])=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 JMHRGKDWGWORNU-UHFFFAOYSA-M 0.000 description 1
- SEEXPXUCHVGZGU-UHFFFAOYSA-M sodium;2-[5-(4-chlorobenzoyl)-1,4-dimethylpyrrol-2-yl]acetate Chemical compound [Na+].C1=C(CC([O-])=O)N(C)C(C(=O)C=2C=CC(Cl)=CC=2)=C1C SEEXPXUCHVGZGU-UHFFFAOYSA-M 0.000 description 1
- VYOUHDLOIRJOSW-UHFFFAOYSA-N sodium;4-butyl-1,2-diphenylpyrazolidin-4-ide-3,5-dione Chemical compound [Na+].C=1C=CC=CC=1N1C(=O)[C-](CCCC)C(=O)N1C1=CC=CC=C1 VYOUHDLOIRJOSW-UHFFFAOYSA-N 0.000 description 1
- AVERBMQHYOZACV-UHFFFAOYSA-M sodium;7-chloro-4-[(3,4-dichlorophenyl)carbamoyl]-1,1-dioxo-2,3-dihydro-1$l^{6}-benzothiepin-5-olate;hydrate Chemical compound O.[Na+].C1CS(=O)(=O)C2=CC=C(Cl)C=C2C([O-])=C1C(=O)NC1=CC=C(Cl)C(Cl)=C1 AVERBMQHYOZACV-UHFFFAOYSA-M 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 229950009641 sparsomycin Drugs 0.000 description 1
- XKLZIVIOZDNKEQ-CLQLPEFOSA-N sparsomycin Chemical compound CSC[S@](=O)C[C@H](CO)NC(=O)\C=C\C1=C(C)NC(=O)NC1=O XKLZIVIOZDNKEQ-CLQLPEFOSA-N 0.000 description 1
- XKLZIVIOZDNKEQ-UHFFFAOYSA-N sparsomycin Natural products CSCS(=O)CC(CO)NC(=O)C=CC1=C(C)NC(=O)NC1=O XKLZIVIOZDNKEQ-UHFFFAOYSA-N 0.000 description 1
- 229950004330 spiroplatin Drugs 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
- 229960001052 streptozocin Drugs 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical group [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- DHCDFWKWKRSZHF-UHFFFAOYSA-N sulfurothioic S-acid Chemical compound OS(O)(=O)=S DHCDFWKWKRSZHF-UHFFFAOYSA-N 0.000 description 1
- 229960000894 sulindac Drugs 0.000 description 1
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
- 229950007841 sulofenur Drugs 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 229960004492 suprofen Drugs 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 201000010965 sweat gland carcinoma Diseases 0.000 description 1
- 206010042863 synovial sarcoma Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 108700003774 talisomycin Proteins 0.000 description 1
- 229950002687 talisomycin Drugs 0.000 description 1
- 229950005100 talmetacin Drugs 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 229960001674 tegafur Drugs 0.000 description 1
- WFWLQNSHRPWKFK-ZCFIWIBFSA-N tegafur Chemical compound O=C1NC(=O)C(F)=CN1[C@@H]1OCCC1 WFWLQNSHRPWKFK-ZCFIWIBFSA-N 0.000 description 1
- 201000004415 tendinitis Diseases 0.000 description 1
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
- 229960001278 teniposide Drugs 0.000 description 1
- WZWYJBNHTWCXIM-UHFFFAOYSA-N tenoxicam Chemical compound O=C1C=2SC=CC=2S(=O)(=O)N(C)C1=C(O)NC1=CC=CC=N1 WZWYJBNHTWCXIM-UHFFFAOYSA-N 0.000 description 1
- 229960002871 tenoxicam Drugs 0.000 description 1
- 229950008703 teroxirone Drugs 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 229950007324 tesicam Drugs 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- TUGDLVFMIQZYPA-UHFFFAOYSA-N tetracopper;tetrazinc Chemical compound [Cu+2].[Cu+2].[Cu+2].[Cu+2].[Zn+2].[Zn+2].[Zn+2].[Zn+2] TUGDLVFMIQZYPA-UHFFFAOYSA-N 0.000 description 1
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 1
- 235000019157 thiamine Nutrition 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- 239000011721 thiamine Substances 0.000 description 1
- 150000003558 thiocarbamic acid derivatives Chemical class 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 210000003813 thumb Anatomy 0.000 description 1
- YFTWHEBLORWGNI-UHFFFAOYSA-N tiamiprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC(N)=NC2=C1NC=N2 YFTWHEBLORWGNI-UHFFFAOYSA-N 0.000 description 1
- 229950011457 tiamiprine Drugs 0.000 description 1
- 229960003723 tiazofurine Drugs 0.000 description 1
- FVRDYQYEVDDKCR-DBRKOABJSA-N tiazofurine Chemical compound NC(=O)C1=CSC([C@H]2[C@@H]([C@H](O)[C@@H](CO)O2)O)=N1 FVRDYQYEVDDKCR-DBRKOABJSA-N 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 229950002345 tiopinac Drugs 0.000 description 1
- 229950002376 tirapazamine Drugs 0.000 description 1
- ORYDPOVDJJZGHQ-UHFFFAOYSA-N tirapazamine Chemical compound C1=CC=CC2=[N+]([O-])C(N)=N[N+]([O-])=C21 ORYDPOVDJJZGHQ-UHFFFAOYSA-N 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 229960001017 tolmetin Drugs 0.000 description 1
- UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 description 1
- 229960002044 tolmetin sodium Drugs 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 229960002190 topotecan hydrochloride Drugs 0.000 description 1
- 229960004167 toremifene citrate Drugs 0.000 description 1
- 238000013271 transdermal drug delivery Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 0.000 description 1
- 229960002117 triamcinolone acetonide Drugs 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- VSVSLEMVVAYTQW-VSXGLTOVSA-N triclonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(Cl)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CCl)[C@@]2(C)C[C@@H]1Cl VSVSLEMVVAYTQW-VSXGLTOVSA-N 0.000 description 1
- 229950008073 triclonide Drugs 0.000 description 1
- 229950000451 triflumidate Drugs 0.000 description 1
- 125000004953 trihalomethyl group Chemical group 0.000 description 1
- NOYPYLRCIDNJJB-UHFFFAOYSA-N trimetrexate Chemical compound COC1=C(OC)C(OC)=CC(NCC=2C(=C3C(N)=NC(N)=NC3=CC=2)C)=C1 NOYPYLRCIDNJJB-UHFFFAOYSA-N 0.000 description 1
- 229960001099 trimetrexate Drugs 0.000 description 1
- VXKHXGOKWPXYNA-PGBVPBMZSA-N triptorelin Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 VXKHXGOKWPXYNA-PGBVPBMZSA-N 0.000 description 1
- 229960004824 triptorelin Drugs 0.000 description 1
- FQCQGOZEWWPOKI-UHFFFAOYSA-K trisalicylate-choline Chemical compound [Mg+2].C[N+](C)(C)CCO.OC1=CC=CC=C1C([O-])=O.OC1=CC=CC=C1C([O-])=O.OC1=CC=CC=C1C([O-])=O FQCQGOZEWWPOKI-UHFFFAOYSA-K 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 230000001228 trophic effect Effects 0.000 description 1
- 208000025883 type III hypersensitivity disease Diseases 0.000 description 1
- 230000005951 type IV hypersensitivity Effects 0.000 description 1
- 229950008396 ulobetasol propionate Drugs 0.000 description 1
- BDSYKGHYMJNPAB-LICBFIPMSA-N ulobetasol propionate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H](C)[C@@](C(=O)CCl)(OC(=O)CC)[C@@]2(C)C[C@@H]1O BDSYKGHYMJNPAB-LICBFIPMSA-N 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- SPDZFJLQFWSJGA-UHFFFAOYSA-N uredepa Chemical compound C1CN1P(=O)(NC(=O)OCC)N1CC1 SPDZFJLQFWSJGA-UHFFFAOYSA-N 0.000 description 1
- 229950006929 uredepa Drugs 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 208000034280 venom allergy Diseases 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- ZQFGRJWRSLZCSQ-ZSFNYQMMSA-N verteporfin Chemical compound C=1C([C@@]2([C@H](C(=O)OC)C(=CC=C22)C(=O)OC)C)=NC2=CC(C(=C2C=C)C)=NC2=CC(C(=C2CCC(O)=O)C)=NC2=CC2=NC=1C(C)=C2CCC(=O)OC ZQFGRJWRSLZCSQ-ZSFNYQMMSA-N 0.000 description 1
- 229960003895 verteporfin Drugs 0.000 description 1
- AQTQHPDCURKLKT-JKDPCDLQSA-N vincristine sulfate Chemical compound OS(O)(=O)=O.C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C=O)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 AQTQHPDCURKLKT-JKDPCDLQSA-N 0.000 description 1
- 229960002110 vincristine sulfate Drugs 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
- 229960005212 vindesine sulfate Drugs 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
- 210000000707 wrist Anatomy 0.000 description 1
- DVPVGSLIUJPOCJ-XXRQFBABSA-N x1j761618a Chemical compound OS(O)(=O)=O.OS(O)(=O)=O.OS(O)(=O)=O.C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(=O)CN(C)C)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21.C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(=O)CN(C)C)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 DVPVGSLIUJPOCJ-XXRQFBABSA-N 0.000 description 1
- 229950009268 zinostatin Drugs 0.000 description 1
- 229960003516 zomepirac sodium Drugs 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/275—Nitriles; Isonitriles
- A61K31/277—Nitriles; Isonitriles having a ring, e.g. verapamil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
- A61K31/37—Coumarins, e.g. psoralen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/423—Oxazoles condensed with carbocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/433—Thidiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4453—Non condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4535—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4741—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having oxygen as a ring hetero atom, e.g. tubocuraran derivatives, noscapine, bicuculline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/475—Quinolines; Isoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/538—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with carbocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/5415—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/566—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol having an oxo group in position 17, e.g. estrone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
- A61K31/688—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols both hydroxy compounds having nitrogen atoms, e.g. sphingomyelins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Emergency Medicine (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
发明领域和背景
本发明在其一些实施方案中涉及疗法,更特别但非排他性地涉及EGR1靶向药物及其用于治疗炎性和过度增殖病况的用途。
罕见单基因疾病的研究经常揭示迄今未知的生物途径。
家族性肿瘤样钙质沉着症(FTC)代表表现为皮肤和皮下钙化材料沉积的临床和遗传异质性的遗传疾病。之前证实,FTC的正常磷酸血症型(normophosphatemic)变体(NFTC)由编码170kD蛋白质的无菌α基序结构域9(SAMD9)基因中的突变造成[Chefetz,I.等人(2008)J Invest Dermatol 128:1423-9]。NFTC以常染色体隐性方式遗传并仅在也门犹太人(Yemenite Jews)中报道。几种炎性细胞因子,包括肿瘤坏死因子α(TNF-α)和干扰素γ(IFN-γ)调节SAMD9基因表达[Chefetz,I.等人(2008),见上文],这可以解释在NFTC中炎症看起来在皮肤中的异位钙化之前的事实。
之前确定,SAMD9可通过抑制EGR1(早期生长反应蛋白1)表达发挥作用[Hershkovitz,D.等人(2011)JInvest Dermatol 131:662-9]。EGR1基因产物是在分化和生长中具有作用的转录因子。EGR1也是炎症的重要介体并可能参与克罗恩氏病的发病机理(其中SAMD9下调)和硬皮病(一种公知表现出异位钙化的障碍)的发病机理。此外,磷酸钙的组织沉积与提高的EGR1表达相关联[Molloy,E.S.和McCarthy,G.M.(2006)Curr OpinRheumatol 18:187-92]。EGR1也已参与乳腺癌、前列腺癌和肺癌的发病机理并可能由于控制肌动蛋白收缩性的基因的活化而对转移进程重要[Cermak,V.等人(2010)Cell Mol LifeSci 67:3557-68]——与显示在SAMD9下调后肌动蛋白丝的细胞内再分布的数据[Hershkovitz,D.等人(2011),见上文]相符的观察。
公开号为20140011812的美国专利申请公开了通过抑制polo样激酶(PlK)减轻炎症的方法,并提到EGR1作为其表达与免疫应答相关联的转录调控因子。
另外的背景技术包括WO 2014/011540和欧洲专利0502668。
发明概述
根据本发明的一些实施方案的一个方面,提供治疗需要其的对象的炎症或过度增殖性疾病的方法,所述方法包括给予所述对象治疗有效量的选自下列的化合物:
式I所示的化合物:
或其可药用盐,
其中:
X是N-R9;
Y选自S(=O)2、C=O或不存在;
R1-R8各自独立地为氢、烷基、环烷基、卤素、三卤烷基、氨基、烷氧基、硫代烷氧基、羟基、巯基(thiol)、硝基、氰基、芳基或杂芳基,或者替代地或附加地,R1-R4和R9的两个和/或R5-R9的两个一起形成环状环,所述环状环选自芳基、杂芳基、环烷基或杂脂环族基团,
式II所示的化合物:
其中:
R10-R13各自独立地为氢、烷基、环烷基、卤素、三卤烷基、氨基、烷氧基、硫代烷氧基、羟基、巯基、硝基、氰基、芳基或杂芳基,或替代地,R10-R13的两个一起形成环状环,所述环状环选自芳基、杂芳基、环烷基或杂脂环族基团;
R14是氢、烷基或环烷基;且
T1和T2各自是卤素,和
式III所示的化合物:
其中:
R15是氢、烷基或环烷基;
R16-R22各自独立地为氢、烷基、环烷基、卤素、三卤烷基、氨基、烷氧基、硫代烷氧基、羟基、巯基、硝基、氰基、芳基或杂芳基,或替代地,R15、R17和R18的两个和/或R15和R19-R22的两个一起形成环状环,所述环状环选自芳基、杂芳基、环烷基和杂脂环族基团,由此治疗所述对象的炎症或过度增殖性疾病。
根据本发明的一些实施方案的一个方面,提供选自如本文所述的式I、式II和式III所示的化合物的化合物在制备用于治疗需要其的对象的炎症或过度增殖性疾病的药物中的用途。
根据本发明的一些实施方案的一个方面,提供用于治疗需要其的对象的炎症或过度增殖性疾病的选自如本文所述的式I、式II和式III所示的化合物的化合物。
根据本发明的一些实施方案,该炎症与慢性炎性疾病相关联。
根据本发明的一些实施方案,该炎症与急性炎性疾病相关联。
根据本发明的一些实施方案,该炎症与选自感染性疾病、自身免疫病、超敏反应相关炎症、移植排斥和损伤的疾病相关联。
根据本发明的一些实施方案,该自身免疫病选自克罗恩氏病、牛皮癣、硬皮病和类风湿性关节炎。
根据本发明的一些实施方案,该炎症包括皮肤炎症。
根据本发明的一些实施方案,该皮肤炎症选自特应性皮炎、接触性皮炎、疱疹样皮炎、泛发性表皮脱落性皮炎、脂溢性皮炎、牛皮癣、药疹、多形性红斑、结节性红斑、环状肉芽肿、毒葛皮炎、毒橡树皮炎(poison oak)、中毒性表皮坏死松解症、痤疮和红斑痤疮。
根据本发明的一些实施方案,该过度增殖性疾病是癌症或癌症转移。
根据本发明的一些实施方案,该癌症选自乳腺癌、前列腺癌、肺癌、神经母细胞瘤、黑素瘤、结肠癌和胰腺癌。
根据本发明的一些实施方案,该过度增殖性疾病是钙化性癌症(calcifiedcancer)。
根据本发明的一些实施方案,该钙化性癌症是FTC的正常磷酸血症型变体(NFTC)。
根据本发明的一些实施方案的一个方面,提供用于治疗癌症的制品,其包含选自式I、式II和式III所示的化合物的化合物和化疗药品(chemotherapy),其包装在包装材料中并在所述包装材料中或上以印刷方式识别。
根据本发明的一些实施方案的一个方面,提供用于治疗炎症的制品,其包含选自如本文所述的式I、式II和式III所示的化合物的化合物和抗炎剂,其包装在包装材料中并在所述包装材料中或上以印刷方式识别。
根据本发明的一些实施方案,式I、II或III所示的化合物和所述化疗药品在分开的容器中。
根据本发明的一些实施方案,式I、II或III所示的化合物和所述抗炎剂在分开的容器中。
根据本发明的一些实施方案,式I、II或III所示的化合物和所述化疗药品在共同制剂(co-formulation)中。
根据本发明的一些实施方案,式I、II或III所示的化合物和所述抗炎剂在共同制剂中。
根据本文所述的任何实施方案的一些,该化合物由式I表示。
根据本文所述的任何实施方案的一些,该化合物是7,9-二氯-5,5-二氧代-10-丙基吩噻嗪-3-胺。
根据本文所述的任何实施方案的一些,该化合物是6H-吡啶并[4,3-b]咔唑-1-甲酰胺,5,11-二甲基-单盐酸盐。
除非另行规定,本文所用的所有技术和/或科学术语具有如本发明所属领域的普通技术人员通常理解的相同含义。尽管在本发明的实施方案的实践或测试中可以使用与本文中描述的那些类似或等同的方法和材料,但下面描述示例性方法和/或材料。如有冲突,以专利说明书,包括定义为准。此外,材料、方法和实施例仅是说明性的并且无意构成必要限制。
附图的若干视图的简述
在本文中参考附图仅作为实例描述本发明的一些实施方案。现在详细地具体参考附图,要强调,所示细节是举例方式并且用于说明性论述本发明的实施方案。在这方面,附图描述使本领域技术人员清楚如何实施本发明的实施方案。
在附图中:
图1A-B图示说明转染HeLa细胞中的SAMD9启动子活性。图1A显示用表达载体pGL4.17本身(无PGL4)或含有在TSS游跨越585bp的SAMD9启动子片段的pGL4.17和pRLRenilla荧光素酶载体上瞬时转染的HeLa细胞。在转染后24小时,加入10ng/ml IFN-γ。将在转染后48小时获得的荧光素酶数据相对于Renilla归一化;图1B显示在添加的10ng/mlIFN-γ存在下培养24小时的稳定表达含有585bp SAMD9启动子片段的表达载体pGL4.17的HeLa细胞系。然后将荧光素酶数据相对于Renilla归一化。
图1C图示说明用CaCx和ApDx处理的HeLa细胞、TERC-转化的成纤维细胞和原代成纤维细胞中的SAMD9表达的诱导。将所有三种细胞类型在12孔板中培养并用5μM CaCx(黑柱)和ApDx(空白柱)一式两份处理24小时。通过qRT-PCR一式三份测量SAMD9表达。结果表示为相对于用DMSO处理的对照细胞的SAMD9 RNA表达的倍数变化+标准误差。*=p<0.05;**=p<0.01。
图2A-B图示说明用CaCx和ApDx处理的原代成纤维细胞中的SAMD9表达的诱导。将原代成纤维细胞一式两份在12孔板中在5μM CaCx和ApDx(空白柱)或DMSO存在下培养72小时(图2A)或在DMSO或分别1μM、2μM、5μM和10μM CaCx或ApDx存在下培养(图2B)。通过qRT-PCR测量SAMD9表达,所有样品一式三份运行。结果表示为相对于用DMSO处理的对照原代成纤维细胞的SAMD9 RNA表达+标准误差。*=p<0.05;**=p<0.01。
图3图示说明CaCx和ApDx对原代成纤维细胞中的EGR1表达的效果。将原代成纤维细胞在12孔板中在DMSO、5μM CaCx(黑柱)或ApDx(空白柱)存在下一式两份培养72小时。结果分别表示为相对于DMSO处理的对照物的EGR1 RNA表达+标准误差。*=p<0.05;**=p<0.01。
图4A-F图示说明CaCx和ApDx对小鼠中的咪喹莫特诱发的银屑病样皮炎的效果的组织病理分析。将三组小鼠如下处理:组1每周5次用咪喹莫特局部处理并接受DMSO的腹腔注射(图4A和4D);组2每周5次用咪喹莫特局部处理并接受CaCx的腹腔注射(图4B和4E);组3每周5次用咪喹莫特局部处理并接受ApDx的腹腔注射(图4C和4F)。在第6天获得活检物(biopsies)并用H&E(上方组)和Ki67(下方组)染色。
图5A-C图示说明在用CaCx和ApDx处理咪喹莫特诱发的银屑病样皮炎后的Ki67染色和表皮厚度。将12只Balb/c小鼠用咪喹莫特5%每天局部处理5天并分成三个等分组,同时接受5天腹腔注射赋形剂(DMSO和脂褐质10%);22.5mg/kg/天CaCx或7.5mg/kg/天ApDx。图5A显示以微米测得的表皮厚度(黑柱)和表皮中的阳性(positive)Ki67的百分比(白色柱);图5B-C,并行地,通过qRT-PCR一式三份测量EGR1 RNA水平(图5B)和IL-33RNA水平(图5C)。CaCx(黑柱)和ApDx(白色柱)。结果表示为相对于用赋形剂处理组处理的对照小鼠的EGR1 RNA表达+标准误差。*=p<0.05;**=p<0.01。
图6图示说明CaCx和ApDx在携带人类银屑病皮肤的嵌合体小鼠中的效果。在人类皮肤移植后六周,处理嵌合体小鼠。如下处理四组小鼠:一组小鼠每周5次腹腔注射赋形剂;第二组小鼠每周5次注射ApDx(5mg/kg);第三组小鼠每周5次注射CaCx(15mg/kg);且第四组小鼠用每周5次施加在移植物上的地塞米松(DEX)乳膏处理,作为阳性对照(DEX预计在这一模型中减弱炎症)。各组包括5只小鼠,该处理进行总共10天。从这四组小鼠收获移植物,将其石蜡包埋,苏木精和曙红(H&E)染色,分析并对临床和组织学银屑病样表型的平均改善评分。结果代表各小鼠组的平均改善分数+SE(*p<0.05;**p<0.001、***p<0.0001)。
图7A-F图示说明CaCx和ApDx在携带人类银屑病皮肤的嵌合体小鼠中的效果的组织病理学分析。如下处理三组小鼠:一组小鼠每周5次腹腔注射赋形剂(图7A和7D);第二组小鼠每周5次注射ApDx(5mg/kg)(图7C和7F);第三组小鼠每周5次注射CaCx(15mg/kg)(图7B和7E)。各组包括5只小鼠,该处理进行总共10天。在第10天获得活检物并用H&E(上方组)和Ki67(下方组)染色。
图8图示说明在用CaCx和ApDx处理后携带人类银屑病皮肤的嵌合体小鼠中的Ki67染色和表皮厚度。将小鼠如上图7A-F中所述处理。显示以微米测得的表皮厚度(黑柱)和表皮中的阳性Ki67的百分比(白色柱)。
图9图示说明在用CaCx处理后携带人类银屑病皮肤的嵌合体小鼠中的EGR1和SAMD9 RNA水平。将小鼠如上图7A-F中所述处理。通过qRT-PCR一式三份测量EGR1(黑柱)和SAMD9(白色柱)RNA水平。结果表示为相对于用赋形剂处理组处理的对照小鼠的RNA表达+标准误差。*=p<0.05;**=p<0.01。
本发明的具体实施方案的描述
本发明在其一些实施方案中涉及疗法,更特别但非排他性地涉及EGR1靶向药物及其用于治疗炎性和过度增殖性病况的用途。
参考附图和所附说明可以更好地理解本发明的原理和操作。
在详细解释本发明的至少一个实施方案之前,要理解的是,本发明在其应用中不一定局限于下列说明书中阐述或通过实施例例举的细节。本发明能有其它实施方案或以各种方式实践或进行。还要理解的是,本文所用的措辞和术语用于描述并且不应被视为限制。
炎症的传统治疗不是从根本上治愈炎症,并且通常具有副作用,如超敏反应和免疫系统恶化。
牛皮癣,一种慢性炎性疾病,影响全球人口的大约2-3%。迄今没有治愈牛皮癣。
本发明的一些发明人之前发现SAMD9的表达或功能的损失造成炎症和随后的钙质沉着。SAMD9通过下调EGR1(炎性反应的一种关键调控因子)的表达发挥作用。
在将本发明付诸实践的同时,本发明人已经通过艰苦的实验和筛选发现SAMD9转录活性的一类小分子诱导剂,其下调EGR1并因此可用于治疗炎性和过度增殖性疾病,包括皮肤病,如牛皮癣。
如本文和下列实施例部分中所述,本发明人生成在功能性SAMD9启动子的调节下稳定表达荧光素酶基因的细胞系并使用这些细胞筛选超过1400种小分子。大约85种筛选分子在初始筛选中表明诱导SAMD9依赖性荧光素酶活性。进一步测试这些分子的SAMD9表达的诱导,并且在这两个测定中都发现为活性的31种示例性化合物示于下表2中。进一步测试这些示例性化合物中的两种,6H-吡啶并[4,3-b]咔唑-1-甲酰胺,5,11-二甲基-,单盐酸盐(CaCx)和10-正-丙基-1,3-二氯-7-氨基-吩噻嗪-5,5-二氧化物(ApDx),并且其在HeLa、TERC-转化的成纤维细胞和原代成纤维细胞中以时间和剂量依赖性方式可再现地诱导SAMD9启动子活性以及内源性SAMD9表达(图1C、2A和2B)。SAMD9的这两种诱导剂下调EGR1的表达(图3)。随后将这两种化合物在体内小鼠模型中评估并发现逆转咪喹莫特诱发的银屑病样皮炎的表皮组织病理学表型(图4A-F和5A-B)。此外,如通过临床分数和通过组织学检查测得的,这两种化合物表明在携带人类银屑病皮肤的嵌合体小鼠模型中减弱银屑病样表型(图6、7A-F、8和9)。
这些数据得出下述理解,如下文更详细描述的,表现出如下文描绘的结构特征的化合物可用作EGR1靶向药物并可用于治疗炎症和过度增殖性疾病或障碍。
因此,根据本发明的一个方面,提供治疗需要其的对象的炎症或过度增殖性疾病的方法,所述方法包括给予所述对象治疗有效量的如本文在任一各自实施方案中描述的式I、II或III所示的化合物,由此治疗所述对象的炎症或过度增殖性疾病。根据本发明的另一方面,提供如本文在任一各自实施方案中描述的式I、II或III所示的化合物在制备用于治疗需要其的对象的炎症或过度增殖性疾病的药物中的用途。根据本发明的另一方面,提供用于治疗需要其的对象的炎症或过度增殖性疾病的如本文在任一各自实施方案中描述的式I、II或III所示的化合物。
本文所用的术语“治疗”是指缓和、减弱、减轻或消除炎症或过度增殖性疾病的症状、减慢、逆转或阻遏炎症或过度增殖性疾病的进展、或治愈炎症或过度增殖性疾病。
本文所用的术语“对象”或“需要其的对象”是指哺乳动物,优选人类,雄性或雌性,在遭受该病理学或在发生该病理学的风险下的任何年龄。
根据一个实施方案,该病理学是炎症或过度增殖性疾病。
炎症
本文所用的术语“炎症”是指由物理损伤、感染或局部免疫反应引起的流体、血浆蛋白和白细胞的局部积聚的通用术语。炎症可能与几个迹象相关联,如发红、疼痛、热、肿和/或功能丧失。炎症是许多疾病和障碍的一个方面,包括但不限于与免疫疾病、病毒和细菌感染、关节炎、自身免疫病、胶原病、过敏、哮喘、花粉病和特应性相关的疾病(如下文更详细描述的)。
因此,损伤,例如对皮肤、肌肉、肌腱或神经的损伤可引发炎症。可作为免疫反应,例如病理性自身免疫反应的一部分引发炎症。感染也可引发炎症,其中病理识别和组织损伤可在感染位点引发炎性反应。
炎症根据本教导可能与慢性(长期)炎性疾病或障碍或急性(短期)炎性疾病或障碍相关联。
根据一个具体实施方案,该炎症与选自感染性疾病、自身免疫病、超敏反应相关炎症、移植排斥和损伤的疾病相关联。
根据一个具体实施方案,该炎症包括皮肤炎症。
根据一个具体实施方案,该皮肤炎症是牛皮癣。
以皮肤炎症为特征的疾病包括但不限于皮炎、特应性皮炎(湿疹、特异反应性)、接触性皮炎、疱疹样皮炎、泛发性表皮脱落性皮炎、脂溢性皮炎、药疹、多形性红斑、结节性红斑、环状肉芽肿、毒葛皮炎、毒橡树皮炎、中毒性表皮坏死松解症、红斑痤疮、牛皮癣和痤疮。炎症也可源自对皮肤的物理损伤。
对肌肉、肌腱或神经的各种损伤可能引发炎症。因此,例如,身体部位的重复运动,即重复性劳损(RSI)可能造成炎症。以RSI引发的炎症为特征的疾病包括,但不限于,滑囊炎、腕管综合征、杜普伊特伦挛缩、上髁炎(例如网球肘)、腱鞘囊肿(即腱鞘中形成的囊肿的炎症,通常发生在手腕上)、旋转袖综合征、腱炎(例如跟腱炎)、腱鞘炎和扳机指(手指或拇指的腱鞘的炎症,伴随着肌腱肿胀)。
许多感染性疾病相关的疾病包括炎性反应,其中炎性反应通常是由入侵的病原体引发的先天免疫系统的一部分。由感染造成的对细胞和组织的物理(机械)损伤也可引发炎症。感染性疾病的实例包括,但不限于,慢性感染性疾病、亚急性感染性疾病、急性感染性疾病、病毒性疾病、细菌性疾病、原虫病、寄生虫病、真菌病、支原体病和朊病毒病。根据一个实施方案,以炎症为特征的感染的实例包括,但不限于,脑炎;脑膜炎;脑脊髓炎;病毒性胃肠炎;病毒性肝炎。
此外,许多免疫疾病包括急性或慢性炎症。例如,关节炎被认为是以关节发炎为特征的免疫疾病,但关节炎同样被认为是以对关节组织的免疫攻击为特征的炎性疾病。
根据本教导的炎症可能与缺陷免疫反应(例如HIV、AIDS)或与过度免疫反应(例如过敏、自身免疫疾病)相关。因此,根据本教导的炎症可能与下列任一种相关:
与超敏反应相关的炎性疾病:
超敏反应的实例包括,但不限于,I型超敏反应、II型超敏反应、III型超敏反应、IV型超敏反应、速发型超敏反应、抗体介导的超敏反应、免疫复合物介导的超敏反应、T淋巴细胞介导的超敏反应和DTH。
I型或速发型超敏反应,如哮喘。
II型超敏反应包括,但不限于,类风湿病、类风湿性自身免疫病、类风湿性关节炎(Krenn V.等人,Histol Histopathol 2000年7月;15(3):791)、脊椎炎、强直性脊柱炎(JanVoswinkel等人,Arthritis Res 2001;3(3):189)、全身性疾病、全身性自身免疫病、全身性红斑狼疮(Erikson J.等人,Immunol Res 1998;17(1-2):49)、硬化症、全身性硬化症(Renaudineau Y.等人,Clin Diagn Lab Immunol.1999年3月;6(2):156);Chan OT.等人,Immunol Rev 1999年6月;169:107)、腺体疾病、腺体自身免疫病、胰腺自身免疫病、糖尿病、I型糖尿病(Zimmet P.Diabetes Res Clin Pract 1996年10月;34Suppl:S125)、甲状腺疾病、自身免疫性甲状腺疾病、格雷夫斯病(Orgiazzi J.Endocrinol Metab Clin North Am2000年6月;29(2):339)、甲状腺炎、自发性自身免疫性甲状腺炎(Braley-Mullen H.和YuS,J Immunol 2000年12月15;165(12):7262)、桥本氏甲状腺炎(ToyodaN.等人,NipponRinsho1999Aug;57(8):1810)、粘液水肿、特发性粘液水肿(Mitsuma T.NipponRinsho.1999年8月;57(8):1759);自身免疫性生殖疾病、卵巢疾病、卵巢自身免疫性疾病(Garza KM.等人,J Reprod Immunol 1998年2月;37(2):87)、自身免疫性抗精子不孕(Diekman AB.等人,Am J Reprod Immunol.2000年3月;43(3):134)、反复流产(Tincani A.等人,Lupus 1998;7Suppl 2:S107-9)、神经退行性疾病、神经系统疾病、神经系统自身免疫病、多发性硬化症(Cross AH.等人,JNeuroimmunol 2001年1月1日;112(1-2):1)、阿尔茨海默氏病(Oron L.等人,J Neural Transm Suppl.1997;49:77)、重症肌无力(Infante AJ.和Kraig E,Int Rev Immunol 1999;18(1-2):83)、运动神经病(Kornberg AJ.J ClinNeurosci.2000年5月;7(3):191)、格林-巴利综合征、神经病和自身免疫性神经病(Kusunoki S.Am J Med Sci.2000年4月;319(4):234)、肌无力疾病、Lambert-Eaton肌无力综合征(Takamori M.Am J Med Sci.2000年4月;319(4):204)、副肿瘤性神经系统疾病、小脑萎缩、副肿瘤性小脑萎缩、非副肿瘤性僵硬人综合征、小脑萎缩、进行性小脑萎缩、脑炎、Rasmussen脑炎、肌萎缩侧索硬化症、西登哈姆氏舞蹈病、抽动秽语综合征、多内分泌腺病、自身免疫性多内分泌腺病(Antoine JC.和Honnorat J.Rev Neurol(Paris)2000年1月;156(1):23);神经病、免疫异常神经病(Nobile-Orazio E.等人,Electroencephalogr ClinNeurophysiol Suppl 1999;50:419);神经性肌强直、获得性神经性肌强直、先天性多发性关节弯曲(Vincent A.等人,Ann N Y Acad Sci.1998年5月13日;841:482)、心血管疾病、心血管自身免疫病、动脉粥样硬化(Matsuura E.等人,Lupus.1998;7Suppl 2:S135)、心肌梗死(Vaarala O.Lupus.1998;7Suppl 2:S132)、血栓形成(Tincani A.等人,Lupus 1998;7Suppl 2:S107-9)、肉芽肿病、韦格纳肉芽肿病、动脉炎、Takayasu动脉炎和川崎综合征(Praprotnik S.等人,Wien Klin Wochenschr 2000年8月25日;112(15-16):660);抗因子VIII自身免疫病(Lacroix-Desmazes S.等人,Semin Thromb Hemost.2000;26(2):157);血管炎、坏死性小血管血管炎、显微镜下多血管炎、Churg-Strauss综合征、肾小球肾炎、寡免疫局灶节段坏死性肾小球肾炎、新月体性肾小球肾炎(Noel LH.Ann Med Interne(Paris).2000年5月;151(3):178);抗磷脂综合征(Flamholz R.等人,J Clin Apheresis 1999;14(4):171);心力衰竭、心力衰竭中的激动剂样β-肾上腺素能受体抗体(Wallukat G.等人,AmJ Cardiol.1999年6月17日;83(12A):75H)、血小板减少性紫癜(Moccia F.Ann Ital MedInt.1999年4月-6月;14(2):114);溶血性贫血、自身免疫性溶血性贫血(Efremov DG.等人,Leuk Lymphoma 1998年1月;28(3-4):285)、胃肠道疾病、胃肠道的自身免疫病、肠道疾病、慢性炎性肠道疾病(Garcia Herola A.等人,Gastroenterol Hepatol.2000年1月;23(1):16)、乳糜泻(Landau YE.和Shoenfeld Y.Harefuah 2000年1月16日;138(2):122)、肌肉组织的自身免疫病、肌炎、自身免疫性肌炎、Sjogren综合征(Feist E.等人,Int ArchAllergy Immunol 2000年9月;123(1):92);平滑肌自身免疫病(Zauli D.等人,BiomedPharmacother 1999年6月;53(5-6):234)、肝病、肝脏自身免疫病、自身免疫性肝炎(MannsMP.J Hepatol 2000年8月;33(2):326)和原发性胆汁性肝硬化(Strassburg CP.等人,EurJ Gastroenterol Hepatol.1999年6月;11(6):595)。
IV型或T细胞介导的超敏反应包括,但不限于,类风湿病、类风湿性关节炎(TischR、McDevitt HO.Proc Natl Acad Sci U S A 1994年1月18日;91(2):437)、全身性疾病、全身性自身免疫病、全身性红斑狼疮(Datta SK.,Lupus 1998;7(9):591)、腺体疾病、腺体自身免疫病、胰腺疾病、胰腺自身免疫病、1型糖尿病(Castano L.和EisenbarthGS.Ann.Rev.Immunol.8:647);甲状腺疾病、自身免疫性甲状腺疾病、格雷夫斯病(SakataS.等人,Mol Cell Endocrinol 1993年3月;92(1):77);卵巢疾病(Garza KM.等人,JReprod Immunol 1998年2月;37(2):87)、前列腺炎、自身免疫性前列腺炎(Alexander RB.等人,Urology 1997年12月;50(6):893)、多腺性综合征、自身免疫性多腺性综合征、I型自身免疫性多腺性综合征(Hara T.等人,Blood.1991年3月1日;77(5):1127)、神经系统疾病、自身免疫性神经系统疾病、多发性硬化症、神经炎、视神经炎(Soderstrom M.等人,JNeurol Neurosurg Psychiatry 1994年5月;57(5):544)、重症肌无力(Oshima M.等人,EurJ Immunol 1990年12月;20(12):2563)、僵硬人综合征(Hiemstra HS.等人,Proc NatlAcad Sci U S A 2001年3月27日;98(7):3988)、心血管疾病、Chagas病中的心脏自身免疫(Cunha-Neto E.等人,J Clin Invest 1996年10月15日;98(8):1709)、自身免疫性血小板减少性紫癜(Semple JW.等人,Blood 1996年5月15日;87(10):4245)、抗辅助性T淋巴细胞自身免疫(Caporossi AP.等人,Viral Immunol 1998;11(1):9)、溶血性贫血(Sallah S.等人,Ann Hematol 1997年3月;74(3):139)、肝病、肝脏自身免疫病、肝炎、慢性活动性肝炎(Franco A.等人,Clin Immunol Immunopathol 1990年3月;54(3):382)、胆汁性肝硬化、原发性胆汁性肝硬化(Jones DE.Clin Sci(Colch)1996年11月;91(5):551)、肾疾病、肾脏自身免疫病、肾炎、间质性肾炎(Kelly CJ.J Am Soc Nephrol 1990年8月;1(2):140)、结缔组织病、耳病、自身免疫性结缔组织病、自身免疫性耳病(Yoo TJ.等人,Cell Immunol 1994年8月;157(1):249)、内耳疾病(Gloddek B.等人,Ann N Y Acad Sci 1997年12月29日;830:266)、皮肤病、表皮病(cutaneous diseases)、真皮病(dermal diseases)、大疱性皮肤病、寻常天疱疮、大疱性类天疱疮和落叶型天疱疮。
迟发型超敏反应的实例包括,但不限于,接触性皮炎和药疹。
T淋巴细胞介导的超敏反应的实例包括,但不限于,辅助性T淋巴细胞和细胞毒性T淋巴细胞。
辅助性T淋巴细胞介导的超敏反应的实例包括,但不限于,Th1淋巴细胞介导的超敏反应和Th2淋巴细胞介导的超敏反应。
自身免疫病:
自身免疫病包括,但不限于,心血管疾病、类风湿病、腺体疾病、胃肠道疾病、表皮病、肝病、神经系统疾病、肌肉疾病、肾疾病、生殖相关疾病、结缔组织病和全身性疾病。
自身免疫性心血管疾病的实例包括,但不限于动脉粥样硬化(Matsuura E.等人,Lupus.1998;7Suppl 2:S135)、心肌梗死(Vaarala O.Lupus.1998;7Suppl 2:S132)、血栓形成(Tincani A.等人,Lupus 1998;7Suppl 2:S107-9)、韦格纳肉芽肿病、Takayasu动脉炎、川崎综合征(Praprotnik S.等人,Wien Klin Wochenschr 2000年8月25日;112(15-16):660)、抗因子VIII自身免疫病(Lacroix-Desmazes S.等人,Semin Thromb Hemost.2000;26(2):157)、坏死性小血管血管炎、显微镜下多血管炎、Churg-Strauss综合征、寡免疫局灶节段坏死性和新月体性肾小球肾炎(Noel LH.Ann Med Interne(Paris).2000年5月;151(3):178)、抗磷脂综合征(Flamholz R.等人,J Clin Apheresis 1999;14(4):171)、抗体诱发的心力衰竭(Wallukat G.等人,Am J Cardiol.1999年6月17日;83(12A):75H)、血小板减少性紫癜(Moccia F.Ann Ital Med Int.1999年4月-6月;14(2):114;Semple JW.等人,Blood1996年5月15日;87(10):4245)、自身免疫性溶血性贫血(Efremov DG.等人,Leuk Lymphoma1998年1月;28(3-4):285;Sallah S.等人,Ann Hematol 1997年3月;74(3):139)、Chagas病中的心脏自身免疫(Cunha-Neto E.等人,J Clin Invest 1996年10月15日;98(8):1709)和抗辅助性T淋巴细胞自身免疫(CaporossiAP.等人,Viral Immunol 1998;11(1):9)。
自身免疫性类风湿病的实例包括,但不限于类风湿性关节炎(Krenn V.等人,Histol Histopathol 2000年7月;15(3):791;Tisch R,McDevitt HO.Proc Natl Acad Sciunits S A1994年1月18日;91(2):437)和强直性脊柱炎(Jan Voswinkel等人,ArthritisRes 2001;3(3):189)。
自身免疫性腺体疾病的实例包括,但不限于,胰腺疾病、I型糖尿病、甲状腺疾病、格雷夫斯病、甲状腺炎、自发性自身免疫性甲状腺炎、桥本氏甲状腺炎、特发性粘液水肿、卵巢自身免疫、自身免疫性抗精子不孕、自身免疫性前列腺炎和I型自身免疫性多腺性综合征。疾病包括,但不限于胰腺的自身免疫病、1型糖尿病(Castano L.和EisenbarthGS.Ann.Rev.Immunol.8:647;Zimmet P.Diabetes Res Clin Pract 1996年10月;34Suppl:S125)、自身免疫性甲状腺疾病、格雷夫斯病(Orgiazzi J.Endocrinol Metab Clin NorthAm 2000年6月;29(2):339;Sakata S.等人,Mol Cell Endocrinol 1993年3月;92(1):77)、自发性自身免疫性甲状腺炎(Braley-Mullen H.和Yu S,J Immunol 2000年12月15日;165(12):7262)、桥本氏甲状腺炎(Toyoda N.等人,Nippon Rinsho 1999年8月;57(8):1810)、特发性粘液水肿(Mitsuma T.Nippon Rinsho.1999年8月;57(8):1759)、卵巢自身免疫(Garza KM.等人,J Reprod Immunol 1998年2月;37(2):87)、自身免疫性抗精子不孕(Diekman AB.等人,Am J Reprod Immunol.2000年3月;43(3):134)、自身免疫性前列腺炎(Alexander RB.等人,Urology 1997年12月;50(6):893)和I型自身免疫性多腺性综合征(Hara T.等人,Blood.1991年3月1日;77(5):1127)。
自身免疫性胃肠道疾病的实例包括,但不限于,慢性炎性肠道疾病(GarciaHerola A.等人,Gastroenterol Hepatol.2000年1月;23(1):16)、乳糜泻(Landau YE.和Shoenfeld Y.Harefuah 2000年1月16日;138(2):122)、结肠炎、回肠炎和克罗恩氏病。
自身免疫性表皮病的实例包括,但不限于,自身免疫性大疱性皮肤病,例如但不限于,寻常天疱疮、大疱性类天疱疮和落叶型天疱疮。
自身免疫性肝病的实例包括,但不限于,肝炎、自身免疫性慢性活动性肝炎(Franco A.等人,Clin Immunol Immunopathol 1990年3月;54(3):382)、原发性胆汁性肝硬化(Jones DE.Clin Sci(Colch)1996年11月;91(5):551;Strassburg CP.等人,Eur JGastroenterol Hepatol.1999年6月;11(6):595)和自身免疫性肝炎(Manns MP.J Hepatol2000年8月;33(2):326)。
自身免疫性神经系统疾病的实例包括,但不限于,多发性硬化症(Cross AH.等人,J Neuroimmunol 2001年1月1日;112(1-2):1)、阿尔茨海默氏病(Oron L.等人,J NeuralTransm Suppl.1997;49:77)、重症肌无力(Infante AJ.和Kraig E、Int Rev Immunol1999;18(1-2):83;Oshima M.等人,Eur J Immunol 1990年12月;20(12):2563)、神经病、运动神经病(Kornberg AJ.J ClinNeurosci.2000年5月;7(3):191);格林-巴利综合征和自身免疫性神经病(Kusunoki S.Am J Med Sci.2000年4月;319(4):234)、肌无力、Lambert-Eaton肌无力综合征(Takamori M.Am J Med Sci.2000年4月;319(4):204);副肿瘤性神经系统疾病、小脑萎缩、副肿瘤性小脑萎缩和僵硬人综合征(Hiemstra HS.等人,Proc NatlAcad Sci units S A 2001年3月27日;98(7):3988);非副肿瘤性僵硬人综合征、进行性小脑萎缩、脑炎、Rasmussen脑炎、肌萎缩侧索硬化症、西登哈姆氏舞蹈病、抽动秽语综合征和自身免疫性多内分泌腺病(Antoine JC.和Honnorat J.Rev Neurol(Paris)2000年1月;156(1):23);免疫异常神经病(Nobile-Orazio E.等人,Electroencephalogr ClinNeurophysiol Suppl 1999;50:419);获得性神经性肌强直、先天性多发性关节弯曲(Vincent A.等人,Ann N Y Acad Sci.1998年5月13日;841:482)、神经炎、视神经炎(Soderstrom M.等人,J Neurol Neurosurg Psychiatry 1994年5月;57(5):544)和神经退行性疾病。
自身免疫性肌肉疾病的实例包括,但不限于,肌炎、自身免疫性肌炎和原发性Sjogren综合征(Feist E.等人,Int Arch Allergy Immunol 2000Sep;123(1):92)和平滑肌自身免疫病(Zauli D.等人,Biomed Pharmacother 1999年6月;53(5-6):234)。
自身免疫性肾疾病的实例包括,但不限于,肾炎和自身免疫性间质性肾炎(KellyCJ.JAm Soc Nephrol 1990年8月;1(2):140)。
与生殖相关的自身免疫病的实例包括,但不限于,反复流产(Tincani A.等人,Lupus 1998;7Suppl 2:S107-9)。
自身免疫性结缔组织病的实例包括,但不限于,耳病、自身免疫性耳病(Yoo TJ.等人,Cell Immunol 1994年8月;157(1):249)和内耳的自身免疫病(Gloddek B.等人,Ann NY Acad Sci 1997年12月29日;830:266)。
自身免疫性全身性疾病的实例包括,但不限于,全身性红斑狼疮(Erikson J.等人,Immunol Res 1998;17(1-2):49)和全身性硬化症(Renaudineau Y.等人,Clin DiagnLab Immunol.1999年3月;6(2):156);Chan OT.等人,Immunol Rev 1999年6月;169:107)。
根据一个实施方案,该自身免疫病是克罗恩氏病、牛皮癣、硬皮病或类风湿性关节炎。
移植排斥疾病:
与移植相关的疾病的实例包括,但不限于,移植排斥、慢性移植排斥、亚急性移植排斥、超急性移植排斥、急性移植排斥和移植物抗宿主病。
过敏性疾病:
过敏性疾病的实例包括,但不限于,哮喘、荨麻疹(hives)、风疹(urticaria)、花粉过敏、尘螨过敏、毒液过敏、化妆品过敏、乳胶过敏、化学品过敏、药物过敏、昆虫叮咬过敏、动物皮屑过敏、带刺植物过敏、毒葛过敏和食物过敏。
过度增殖性疾病:
本文所用的术语“过度增殖性疾病”是指涉及不受控的细胞生长的任何病况,即通过快速细胞分裂的异常高速细胞增殖。
本发明不限于特定类型的过度增殖性疾病或障碍并可包括肿瘤、癌症、肿瘤组织以及恶变前和非肿瘤性或非恶性过度增殖性障碍。
在一些实施方案中,该过度增殖性障碍是癌症,包括但不限于癌(carcinoma)、淋巴瘤、胚细胞瘤、肉瘤和白血病。该癌症可包括实体瘤、转移以及混合瘤。癌性疾病的特定实例包括但不限于:纤维肉瘤、粘液肉瘤、脂肪肉瘤、软骨肉瘤、骨肉瘤、脊索瘤、血管肉瘤、内皮肉瘤、淋巴管肉瘤、淋巴管内皮肉瘤、滑膜瘤、间皮瘤、尤因氏瘤、平滑肌肉瘤、横纹肌肉瘤、结肠癌、结肠癌、胰腺癌、乳腺癌、卵巢癌、前列腺癌、鳞状细胞癌、基底细胞癌、腺癌、汗腺癌、皮脂腺癌、乳头状癌、乳头状腺癌、囊腺癌、髓样癌、支气管癌、肾细胞癌、肝癌、胆管癌、绒毛膜癌、精原细胞瘤、胚胎性癌、维尔姆斯瘤、宫颈癌、睾丸肿瘤、肺癌、肺癌、小细胞肺癌、膀胱癌、上皮癌、神经胶质瘤、星形细胞瘤、成神经管细胞瘤、颅咽管瘤、室管膜瘤、松果体瘤、成血管细胞瘤、听神经瘤、少突神经胶质瘤、脑膜瘤、黑素瘤、神经母细胞瘤、成视网膜细胞瘤、膀胱癌、白血病(例如骨髓性白血病,如慢性髓细胞性白血病;伴成熟型急性髓细胞性白血病;急性早幼粒细胞白血病;嗜碱粒细胞增多型急性非淋巴细胞白血病;急性单核细胞性白血病;嗜酸粒细胞增多型急性单核细胞性白血病)、淋巴瘤(例如恶性淋巴瘤,如Birkitt's Non-Hodgkin's;淋巴细胞白血病,如急性淋巴细胞白血病;慢性淋巴细胞白血病)、肾癌、子宫癌和卵巢癌。
如所提到的,本发明的教导还考虑通常与炎症相关联的过度增殖性疾病(例如癌症和牛皮癣)的治疗。根据一个实施方案,本发明的教导考虑癌症,例如转移癌,也称作癌症转移的治疗。
根据一个实施方案,该过度增殖性疾病是钙化性癌症或肿瘤。根据本发明的一个实施方案的钙化性癌症或肿瘤可以是家族性肿瘤样钙质沉着症的正常磷酸血症型变体(NFTC)。
对SAMD9和EGR1活性的影响:
根据本发明的一些实施方案并且不受理论限制,表明如本文所述的化合物有效活化SAMD9以由此下调EGR1活性。
本文所用的术语SAMD9是指含有9的无菌α基序结构域,例如人类SAMD9,例如如GenBank accession nos.NM_017654.3或NM_001193307.1和NP_060124.2或NP_001180236.1(分别是mRNA和蛋白质)中列出。
因此,根据一个实施方案,与治疗前的对象的细胞中(或在具有与需要其的对象相同的病理学并优选与相同物种,例如人类、年龄、体重、性别等匹配的另一对象的相应样品中)的SAMD9的活性或表达相比,本实施方案的化合物将SAMD9的活性或表达上调大约10%、20%、30%、40%、50%、60%、70%、80%、90%、100%或更多。
本文所用的术语EGR1是指早期生长反应蛋白1,如人类EGR1,例如如GenBankaccession nos.NM_001964.2和NP_001955.1(分别是mRNA和蛋白质)中列出。
因此,根据一个实施方案,与治疗前的对象的细胞中(或在具有与需要其的对象相同的病理学并优选与相同物种,例如人类、年龄、体重、性别等匹配的另一对象的相应样品中)的EGR1的活性或表达相比,本发明的化合物将EGR1的活性或表达下调大约10%、20%、30%、40%、50%、60%、70%、80%、90%或100%
化合物:
本实施方案的化合物在本文通篇可互换地称作“化合物”、“分子”、“治疗活性剂”、“药物”或“EGR1靶向药物”。
本文所述的任一实施方案内可用的化合物可以集体由如本文所述的式I、II或III表示。
根据本文所述的任何实施方案的一些,可用于本文所述的任何方法和用途的化合物集体由如本文中定义的式I或其可药用盐表示:
其中:
X是N-R9;
Y选自S(=O)2、C=O或不存在;
R1-R8各自独立地为氢、烷基、环烷基、卤素、三卤烷基、氨基、烷氧基、硫代烷氧基、羟基、巯基、硝基、氰基、芳基或杂芳基,或者替代地或附加地,R1-R4和R9的两个和/或R5-R9的两个一起形成环状环,所述环状环选自芳基、杂芳基、环烷基或杂脂环族基团。
根据一些实施方案,Y是S(=O)2。
根据这些实施方案的一些,R9是氢(H)。
根据这些实施方案的一些,R9是烷基,如甲基、乙基、丙基、异丙基、丁基等。
根据一些实施方案,Y是S(=O)2,且R9是烷基,例如丙基。
根据一些实施方案,R1-R4各自是氢。
根据一些实施方案,R1-R4的至少一个是取代基(即非氢)。
根据一些实施方案,R1-R4的至少一个是卤素,例如氯。
根据一些实施方案,R1-R4的至少两个独立地为卤素,例如氯。
根据一些实施方案,Y是S(=O)2,且R9是烷基,例如丙基,R1和R4各自是氢且R3和R2各自是氯。
根据这些实施方案的一些,R5-R8各自是氢。此类化合物在本文中被称作ApDx。
或者,R5-R8的一个或多个是取代基(即非氢)。
再或者,对于本文中对式I的化合物所述的任何实施方案,R1-R4和R9的两个和/或R5-R9的两个一起形成环状环。
在本文中,“环状环”描述通常5-或–元环,其任选被取代。按其定义,形成的环稠合到一个或多个芳环上和/或稠合到它们之间的中间环上。
根据形成该环的取代基,该环可以是碳环,即如本文所述的任选稠合到另一个环上的芳环(如本文中定义的取代或未取代芳基)或非芳环(如本文中定义的取代或未取代环烷基),或杂环,即如本文所述的任选稠合到另一个环上的如本文中定义的取代或未取代杂脂环族基团或杂芳环(如本文中定义的取代或未取代的杂芳基)。
例如,当R9和R1形成环时,该环是杂环。
当R1-R4的两个形成环且R1-R4的一个或多个是胺、羟基、巯基、硫酸酯基、磺酸酯基、酰胺等时,形成的环是杂环。
当R1-R4的两个形成环且各自是烷基时,形成的环是碳环。
根据与本文中的式I相关的一些实施方案,Y是C(=O)。
根据这些实施方案的一些,R9是氢(H)。
根据这些实施方案的一些,R9是烷基,如甲基、乙基、丙基、异丙基、丁基等。
根据这些实施方案的一些,R1-R4各自是氢。
根据这些实施方案的一些,R1-R4的至少一个是取代基(即非氢)。
根据一些实施方案,R1-R4的至少一个是胺,优选取代的胺。
根据一些实施方案,Y是C(=O)且R9是烷基,R1和R4各自是取代的胺且R3和R2各自是氢。
根据这些实施方案的一些,R5-R8各自是氢。
或者,R5-R8的一个或多个是取代基(即非氢)。
根据这些实施方案的一些,R5-R8的一个或多个是取代基,如本文中定义的羟基、巯基、烷氧基或硫代烷氧基。
再或者,对于本文对式I的化合物描述的任何实施方案,R1-R4和R9的两个和/或R5-R9的两个一起形成环状环。
根据一些实施方案,R1和R9一起形成环状环。
根据这些实施方案的一些,R1和R9一起形成杂环,且在一些实施方案中,该杂环是杂芳基。
在本文所述的式I的任何实施方案的一些中,Y是C(=O),R1和R9一起形成杂芳基,且该杂芳基是1H-咪唑,任选2-甲基-1H-咪唑,其稠合到带有R1的芳环和带有R9的环上,由此形成如表2中对化合物637993描绘的完全共轭的三环芳族体系。
在这些实施方案的一些中,R7是甲氧基,尽管可考虑如本文所述的任何其它取代基。
在这些实施方案的一些中,R3是取代的胺,且该胺优选被氨基烷基取代。在一些实施方案中,该氨基烷基是如作为非限制性实例对表2中的化合物637993描绘的二烷基氨基烷基。
根据一些实施方案,此类化合物可用于治疗如本文所述的除癌症外的炎症或过度增殖性疾病。
根据与如本文所述的式I相关的一些实施方案,Y不存在。此类化合物具有稠合到式I中的芳环上并位于芳环之间的五元环。
根据这些实施方案的一些,R9是H。
根据这些实施方案的一些,R9是烷基,如甲基、乙基、丙基、异丙基、丁基等,并且在一些实施方案中,R9是取代的烷基。
在一些实施方案中,R9是取代的烷基,并且取代基是如本文所述的O-羧酸酯基(O-carboxylate)。在一些实施方案中,该烷基被苯甲酸酯基取代。在一些实施方案中,R9是苯甲酸乙酯。
在如本文所述的式I的任何实施方案的一些中,当Y不存在时,R1-R4各自是氢。但是,R1-R4的一个或多个可以是如本文所述的取代基,或两个或更多个可形成如本文所述的环。
在如本文所述的式I的任何实施方案的一些中,当Y不存在时,R5-R8的一个或多个是烷基。在一些实施方案中,R5和R8各自独立地为烷基并且在一些实施方案中,R5和R8各自是甲基。
在如本文所述的式I的任何实施方案的一些中,当Y不存在时,R5和R8的两个或更多个形成如本文中定义的环状环,并且在一些实施方案中,该环状环是杂芳基,例如吡啶。在这些实施方案的一些中,R6和R7形成吡啶。
在式I的一些实施方案中,Y不存在,R9如本文所述,R1-R4各自是氢,R5和R8各自是烷基,如甲基,且R6和R7形成环,优选吡啶。一种示例性的此类化合物是CaCx(见表2)。另一示例性的化合物是表2中的化合物163433。
在一些实施方案中,此类化合物可用于治疗如本文所述的炎症和过度增殖性疾病,其中该疾病不是寄生虫病(由寄生虫引起的疾病)。
根据本文所述的任何实施方案的一些,可用于本文所述的任何方法和用途的化合物集体由式II表示:
其中:
R10-R13各自独立地为氢、烷基、环烷基、卤素、三卤烷基、氨基、烷氧基、硫代烷氧基、羟基、巯基、硝基、氰基、芳基或杂芳基,或替代地,R10-R13的两个一起形成环状环,所述环状环选自芳基、杂芳基、环烷基或杂脂环族基团;
R14是氢、烷基或环烷基;且
T1和T2各自是卤素。
在这些实施方案的一些中,R10-R13.
在一些实施方案中,R14是氢。
在一些实施方案中,T1和T2各自是氯。
在这些实施方案的一些中,该化合物是二氯2-羟基-1,4-萘醌(Dichlorolawsone)(见表2中的化合物126771),一种天然提取化合物。
根据本文所述的任何实施方案的一些,可用于本文所述的任何方法和用途的化合物集体由式III表示:
其中:
R15是氢、烷基或环烷基;
R16-R22各自独立地为氢、烷基、环烷基、卤素、三卤烷基、氨基、烷氧基、硫代烷氧基、羟基、巯基、硝基、氰基、芳基或杂芳基,或替代地,R15、R17和R18的两个和/或R15、R19-R22的两个一起形成环状环,所述环状环选自芳基、杂芳基、环烷基和杂脂环族基团。
在这些实施方案的一些中,R15是甲基。
在这些实施方案的任何一些中,R17和R18各自是氢。
在这些实施方案的任何一些中,R17和R18各自是氢。
在这些实施方案的任何一些中,R21和R22之一或两者是烷基。在一些实施方案中,R21和R22各自是烷基,且在一些实施方案中该烷基是甲基。
此类化合物被称作黄木灵N(XanthoxylinN)(见表2中的化合物35542)。
根据一些实施方案,当该化合物由式II或III表示时,该炎症或过度增殖性疾病与微生物感染不相关。
对于本文所述的任何实施方案,该化合物可以是盐,例如可药用盐的形式,和/或前药形式。
本文所用的短语“可药用盐”是指母体化合物的带电荷物类及其抗衡离子,其通常用于改变母体化合物的溶解特性和/或降低母体化合物对生物体的任何明显刺激,同时不消除所给药化合物的生物活性和性质。
本文所用的术语“前药”是指在体内转化成活性化合物(例如上述式的化合物)的化合物。前药通常旨在促进给药,例如通过增强吸收。前药可包含例如用酯基团改性的活性化合物,其中该化合物的任何一个或多个羟基被酰基,任选(C1-4)酰基(例如乙酰基)改性以形成酯基团。
此外,本文所述的各化合物,包括其盐可以是其溶剂合物或水合物的形式。
术语“溶剂合物”是指由溶质(本文所述的杂环化合物)和溶剂形成的化学计量可变的复合物(例如二-、三-、四-、五-、六-等),由此该溶剂不干扰溶质的生物活性。
术语“水合物”是指如上文定义的溶剂合物,其中溶剂是水。
当该化合物表现出多晶型时,本实施方案进一步包括如本文所述的化合物的任何同形体。
药物组合物:
本发明的一些实施方案的化合物(EGR1靶向药物)可以本身或在与合适的载体或赋形剂混合的药物组合物中给药至生物体。
本文所用的“药物组合物”是指一种或多种本文所述的活性成分与其它化学组分如生理学合适的载体和赋形剂的制品。药物组合物的目的是促进化合物给药至生物体。
在本文中,术语“活性成分”是指产生生物效果的EGR1靶向药物。
在下文中,可互换使用的短语“生理可接受载体”和“可药用载体”是指不会对生物体造成明显刺激并且不会消除所给药化合物的生物活性和性质的载体或稀释剂。在这些短语下包括佐剂。
在本文中,术语“赋形剂”是指为进一步促进活性成分的给药而添加到药物组合物中的惰性物质。赋形剂的实例非限制性地包括碳酸钙、磷酸钙、各种糖和淀粉类型、纤维素衍生物、明胶、植物油和聚乙二醇。
药物的配制和给药技术可见于“Remington’s Pharmaceutical Sciences,”MackPublishing Co.,Easton,PA,最新版本,其经此引用并入本文。
合适的给药途径可以例如包括口服、直肠、经粘膜,尤其是经鼻,肠内或肠胃外给药,包括肌肉内、皮下和髓内注射以及鞘内、直接心室内、心脏内,例如注射到右或左心室腔中、注射到总冠状动脉中,静脉、腹膜、鼻内或眼内注射。
根据一个实施方案,该EGR1靶向药物配制用于皮肤,例如局部给药(例如给药至角蛋白组织,如皮肤、头皮)、皮下、真皮透皮给药。例如,本发明的一些实施方案的药物组合物配制成乳膏、洗液、喷雾剂、软膏、油膏、凝胶、油、洗剂等以施加或涂铺到身体表面,即皮肤、头皮、头发、指甲等上,优选在皮肤上或靠近发炎处(例如牛皮癣)。
给药至中枢神经系统(CNS)的传统方法包括:神经外科措施(例如大脑内注射或脑室内输注);试剂的分子操作(例如制造包含对内皮细胞表面分子具有亲合力的转运肽以及本身不能穿过BBB的试剂的嵌合蛋白)以试图利用BBB的内源性转运途径之一;旨在提高试剂的脂溶性的药理措施(例如水溶性试剂缀合到脂质体或胆甾醇载体上);和通过高渗性破坏(来源于将甘露糖醇溶液输注到颈动脉中或使用生物活性剂,如血管紧张素肽)暂时破坏BBB的完整性。但是,这些措施各自具有限制,例如与侵入性外科手术相关的固有风险、由内源性转运系统中的固有限制造成的尺寸限制、与由可能在CNS外有活性的载体基序构成的嵌合分子的全身给药相关的可能不合意的生物副作用,和在BBB受到破坏的脑区域内可能的脑损伤风险,这使其成为非最佳的给药方法。
或者,可以以局部而非全身方式给药该药物组合物,例如通过将该药物组合物直接注射到患者的组织区域中。
本发明的一些实施方案的药物组合物可以通过本领域中公知的方法制备,例如借助传统的混合、溶解、制粒、制糖衣丸(dragee-making)、磨细、乳化、包囊、包埋(entrapping)或冻干法。
根据本发明的一些实施方案使用的药物组合物因此可以使用有利于将活性成分加工成可药用制剂的一种或多种生理可接受载体(包含赋形剂和佐剂)以传统方式配制。适当的制剂取决于所选的给药途径。
对于注射,该药物组合物的活性成分可以在水溶液中,优选在生理相容的缓冲剂,如Hank溶液、林格氏溶液或生理盐缓冲液中配制。对于经粘膜给药,在该制剂中使用适合穿透屏障的渗透剂。这样的渗透剂是本领域中公知的。
对于口服给药,容易通过合并活性化合物与本领域中公知的可药用载体配制药物组合物。此类载体能将该药物组合物配制成片剂、丸剂、糖衣丸、胶囊剂、液体、凝胶剂、糖浆剂、浆剂(slurries)、混悬剂等,以供患者口服摄入。用于口服使用的药物制剂可以使用固体赋形剂制备,在视需要加入合适的佐剂后任选研磨所得混合物并加工该颗粒混合物以获得片剂或糖衣丸核。合适的赋形剂特别是填料,如糖,包括乳糖、蔗糖、甘露糖醇或山梨糖醇;纤维素制品,例如玉米淀粉、小麦淀粉、稻米淀粉、马铃薯淀粉、明胶、黄蓍胶、甲基纤维素、羟丙基甲基-纤维素、羧甲基纤维素钠;和/或生理可接受聚合物,如聚乙烯基吡咯烷酮(PVP)。如果需要,可以加入崩解剂,如交联聚乙烯基吡咯烷酮、琼脂或藻酸或其盐,如藻酸钠。
为糖衣丸核提供合适的包衣。为此,可以使用浓缩糖溶液,其可任选含有阿拉伯树胶、滑石、聚乙烯基吡咯烷酮、卡波姆凝胶(carbopol gel)、聚乙二醇、二氧化钛、漆(lacquer)溶液和合适的有机溶剂或溶剂混合物。可以将染料或颜料添加到片剂或糖衣丸包衣中以识别或表征活性化合物剂量的不同组合。
可口服使用的药物组合物包括由明胶制成的硬胶囊(push-fit capsules)以及由明胶和增塑剂,如甘油或山梨糖醇制成的软密封胶囊。该硬胶囊可含有与填料如乳糖、粘合剂如淀粉、润滑剂如滑石或硬脂酸镁和任选稳定剂混合的活性成分。在软胶囊中,可以将活性成分溶解或悬浮在合适的液体,如脂肪油、液体石蜡或液体聚乙二醇中。此外,可以加入稳定剂。用于口服给药的所有制剂应该为适合所选给药途径的剂量。
对于口腔含化(buccal)给药,该组合物可以是以传统方式配制的片剂或锭剂形式。
对于通过鼻吸入给药,根据本发明的一些实施方案使用的活性成分方便地以使用合适的抛射剂,例如二氯二氟甲烷、三氯氟甲烷、二氯-四氟乙烷或二氧化碳从加压包装或雾化器中提供的气雾剂喷雾形式给药。在加压气雾剂的情况下,可以通过提供递送计量量的阀决定剂量单位。可以配制含有化合物和合适的粉末基料如乳糖或淀粉的粉末混合物的用于分配器的例如明胶的胶囊和药筒(cartridge)。
本文所述的药物组合物可以配制用于肠胃外给药,例如通过团注(bolusinjection)或连续输注。注射制剂可以以单位剂型存在,例如在含有任选添加的防腐剂的安瓿或多剂量容器中。该组合物可以是在油性或水性赋形剂中的混悬剂、溶液剂或乳剂,并可含有配制剂,如悬浮剂、稳定剂和/或分散剂。
用于肠胃外给药的药物组合物包括水溶形式的活性制剂的水溶液。另外,活性成分的混悬剂可以制备为适当的油基或水基注射混悬剂。合适的亲脂性溶剂或赋形剂包括脂肪油,如芝麻油,或合成脂肪酸酯,如油酸乙酯、甘油三酯或脂质体。水性注射混悬剂可含有提高该混悬剂的粘度的物质,如羧甲基纤维素钠、山梨糖醇或葡聚糖。任选地,该混悬剂还可含有合适的稳定剂或提高活性成分的溶解度以允许制备高度浓缩溶液的试剂。
或者,活性成分可以为粉末形式以在使用前与合适的赋形剂,例如无菌无热原水基溶液构造。
本发明的一些实施方案的药物组合物也可以使用例如传统栓剂基料,如可可脂或其它甘油酯配制为直肠组合物,如栓剂或保留灌肠剂。
对于局部给药,该药物组合物可以配制为制药工业用于皮肤施加的各种形式的任一种,包括如下所述的溶液、洗液、喷雾剂、乳膏、软膏、油膏、凝胶、油、洗剂等。
本发明的药物组合物可配制得足够粘稠以留在处理的皮肤区域上,不容易蒸发和/或不容易水洗除去,但可借助皂、清洁剂和/或洗发水除去。
制备具有这些性质的组合物的方法是本领域技术人员公知的并详细描述在Remington's Pharmaceutical Sciences,1990(见上文);和Pharmaceutical DosageForms and Drug Delivery Systems,第六版,Williams&Wilkins(1995)中。
本发明的局部组合物,包括但不限于洗液和乳膏,可含有皮肤学可接受的润肤剂。本文所用的“润肤剂”是指可用于防止或缓和干燥以及用于保护皮肤的材料。多种多样的合适润肤剂是已知的并可用于本文。参见例如Sagarin,Cosmetics,Science andTechnology,第2版,第1卷,第3243及之后的页(1972),其含有适合作为润肤剂的材料的许多实例并经此引用完全并入本文。示例性润肤剂包括,但不限于,甘油、烃油和蜡,如矿物油、矿脂等,植物和动物油和脂肪,如橄榄油、棕榈油、蓖麻油、玉米油、大豆油等,和羊毛脂及其衍生物,如羊毛脂、羊毛脂油、羊毛脂蜡、羊毛脂醇等。
本发明的局部施加的药物组合物还可包含例如为了使该药物组合物富含香味和皮肤营养因子而添加的附加组分。
选择在合理医疗判断的范围内适用于人类角蛋白组织而不引起毒性、不相容性、不稳定性、过敏反应等的此类组分。此外,只要它们不会不可接受地改变本发明的活性化合物的益处,此类任选组分就可用。
本发明的药物组合物可以直接施加到皮肤上。或者,其可以通过用本领域中已知的各种经皮给药系统(如以缓释方式将该组合物释放到皮肤中的透皮贴剂)经由正常皮肤施加给药。本领域中已知的其它给药系统包括加压气雾剂瓶、离子电渗法或超声促渗法。离子电渗法用于提高皮肤渗透性并促进经皮给药。美国专利5,667,487和5,658,247公开了适用于超声-离子电渗介导输送治疗剂穿透皮肤的离子超声(ionosonic)装置。替代地或附加地,也可以使用脂质体或胶束作为递送载体。
该药物组合物可配制为单位剂型。在这样的形式中,将该制剂细分成含有例如用于单次给药的适当量的活性成分的单位剂量。该单位剂型可以是包装制剂(该包装含有离散量的制剂),例如粘性绷带、非粘性绷带、擦拭巾、婴儿擦拭巾、纱布、衬垫和卫生巾。
可以根据特定用途改变或调节单位剂量的制剂中的活性化合物的量。
适用于本发明的一些实施方案的药物组合物包括其中以有效实现预期用途的量包含活性成分的组合物。更具体地,治疗有效量是指有效预防、治疗或减轻炎性反应(例如抗炎作用)或过度增殖性疾病(例如抗肿瘤作用)或延长治疗对象的存活期的活性成分(EGR1靶向药物)的量。可以通过本领域技术人员已知的任何方法(例如验血、超声、X-射线、CT扫描、MRI等)以常规方式确定EGR1靶向药物的“治疗有效量”。
因此,治疗有效量的确定完全在本领域技术人员的能力范围内,尤其是根据本文中提供的详细公开。
对于本发明的方法中所用的任何制剂,可以一开始由体外和细胞培养测定估算治疗有效量或剂量。例如,可以在动物模型中配制剂量以实现所需浓度或滴定度。此类信息可用于更精确地测定在人类中的有用剂量。
可通过在体外、在细胞培养或实验动物中的标准药物程序测定本文所述的活性成分的毒性和治疗效力。获自这些体外和细胞培养测定和动物研究的数据可用于配制用于人类的一系列剂量。该剂量可随所用剂型和所用给药途径而变。各医师可根据患者的状况选择确切制剂、给药途径和剂量(参见例如Fingl等人,1975,"The Pharmacological Basisof Therapeutics",第1章第1页)。
可以独立地调节剂量和间隔以提供足以引发或抑制生物效应的足量活性成分(最低有效浓度,MEC)。MEC会随各制剂而变,但可由体外数据估算。实现MEC所必需的剂量取决于个体特征和给药途径。可以使用检测测定确定血浆浓度。
根据待治疗的病况的严重程度和响应能力,给药可以是单次或多次给药,治疗过程持续几天至几周或直至治愈或实现疾病状态的减轻。
待给药的组合物的量当然取决于治疗的对象、痛苦的严重程度、给药方式、处方医师的判断等。
要认识到,该制品可进一步包含另一活性成分以改进治疗效力。因此例如,本发明的分子可以与抗癌治疗剂,例如化疗剂、免疫疗法、放射疗法和/或与用于治疗炎症的试剂,例如抗炎剂组合给药。因此,例如,EGR1靶向药物可以包装在一个容器中,而化疗剂或抗炎剂可以包装在第二个容器中,两者都用于治疗。
根据一个实施方案,该EGR1靶向药物和化疗药品在共同制剂中。
根据另一实施方案,该EGR1靶向药物和抗炎剂在共同制剂中。
本文所用的术语“化疗药品(chemotherapy)”或“化疗剂(chemotherapeutic)”是指在具有肿瘤疾病(例如癌症)的对象中减轻、预防、缓解、限制和/或延迟肿瘤或转移瘤的生长或直接通过肿瘤的坏死或凋亡或任何其它机制杀死赘生细胞或可以治疗有效量以其它方式用于减轻、预防、缓解、限制和/或延迟肿瘤或转移瘤的生长的试剂。
化疗剂包括,但不限于,氟嘧啶;嘧啶核苷;嘌呤核苷;抗叶酸剂(anti-folates)、铂剂;蒽环类/蒽二酮类;表鬼臼毒素;喜树碱(例如Karenitecin);激素;激素复合物;抗激素剂;酶、蛋白质、肽和多克隆和/或单克隆抗体;免疫剂;长春花碱类;紫杉烷类;埃博霉素;抗微管剂;烷基化剂;抗代谢物;拓扑异构酶抑制剂;抗病毒剂;和各种其它细胞毒性剂和细胞生长抑制剂。
根据一个具体实施方案,该化疗剂包括,但不限于阿西维辛;阿柔比星;盐酸阿考达唑(Acodazole Hydrochloride);阿克罗宁;阿霉素;阿多来新(Adozelesin);阿地白介素(Aldesleukin);六甲蜜胺;安波霉素(Ambomycin);乙酸阿美蒽醌(Ametantrone Acetate);氨鲁米特;安吖啶;阿那曲唑;氨茴霉素(Anthramycin);天冬酰胺酶;曲林菌素(Asperlin);阿扎胞苷;阿扎替派(Azetepa);阿佐霉素(Azotomycin);巴马司他(Batimastat);苯佐替派(Benzodepa);比卡鲁胺;盐酸比生群(Bisantrene Hydrochloride);二甲磺酸双萘法德(Bisnafide Dimesylate);比折来新(Bizelesin);硫酸博莱霉素;布喹那钠(BrequinarSodium);溴匹立明(Bropirimine);白消安;放线菌素(Cactinomycin);卡普睾酮(Calusterone);卡醋胺(Caracemide);卡贝替姆(Carbetimer);卡铂;卡莫司汀;盐酸卡米诺霉素(Carubicin Hydrochloride);卡折来新(Carzelesin);西地芬戈(Cedefingol);苯丁酸氮芥;西罗霉素(Cirolemycin);顺铂;克拉屈滨;甲磺酸克立那托(CrisnatolMesylate);环磷酰胺;阿糖胞苷;达卡巴嗪;放线菌素;盐酸柔红霉素;地西他滨;右奥马铂(Dexormaplatin);地扎胍宁(Dezaguanine);甲磺酸地扎胍宁(Dezaguanine Mesylate);地吖醌(Diaziquone);多西他赛;多柔比星;盐酸多柔比星;屈洛昔芬(Droloxifene);柠檬酸屈洛昔芬(Droloxifene Citrate);丙酸屈他雄酮(Dromostanolone Propionate);达佐霉素(Duazomycin);依达曲沙(Edatrexate);盐酸依氟鸟氨酸;依沙芦星(Elsamitrucin);恩洛铂(Enloplatin);恩普氨酯(Enpromate);依匹哌啶(Epipropidine);盐酸表柔比星;厄布洛唑(Erbulozole);盐酸依索比星(Esorubicin Hydrochloride);雌莫司汀;雌莫司汀磷酸钠;依他硝唑(Etanidazole);依托泊苷;磷酸依托泊苷;Etoprine;盐酸法倔唑(FadrozoleHydrochloride);法扎拉滨(Fazarabine);芬维A胺(Fenretinide);氟尿苷;磷酸氟达拉滨;氟尿嘧啶;氟西他滨(Flurocitabine);磷喹酮(Fosquidone);福司曲星钠(FostriecinSodium);吉西他滨;盐酸吉西他滨;羟基脲;盐酸伊达比星;异环磷酰胺;依莫福新(Ilmofosine);干扰素α-2a;干扰素α-2b;干扰素α-n1;干扰素α-n3;干扰素β-Ia;干扰素γ-Ib;异丙铂(Iproplatin);盐酸伊立替康;醋酸兰瑞肽;来曲唑;醋酸亮丙瑞林;盐酸利阿唑(Liarozole Hydrochloride);洛美曲索钠(Lometrexol Sodium);洛莫司汀;盐酸洛索蒽醌(Losoxantrone Hydrochloride);马索罗酚(Masoprocol);美登素(Maytansine);盐酸氮芥;醋酸甲地孕酮;醋酸美仑孕酮;美法仑;美诺立尔(Menogaril);巯基嘌呤;甲氨蝶呤;甲氨蝶呤钠;氯苯氨啶(Metoprine);美妥替哌(Meturedepa);米丁度胺(Mitindomide);米托卡西(Mitocarcin);米托罗明(Mitocromin);米托洁林(Mitogillin);丝裂马菌素(Mitomalcin);丝裂霉素;米托司培(Mitosper);米托坦(Mitotane);盐酸米托蒽醌;麦考酚酸;诺考达唑;诺加霉素;奥马铂(Ormaplatin);奥昔舒仑(Oxisuran);紫杉醇;培门冬酶;培利霉素(Peliomycin);奈莫司汀(Pentamustine);硫酸培洛霉素;培磷酰胺(Perfosfamide);哌泊溴烷(Pipobroman);哌泊舒凡(Piposulfan);盐酸吡罗蒽醌(Piroxantrone Hydrochloride);光神霉素;普洛美坦(Plomestane);卟吩姆钠(PorfimerSodium);泊非霉素(Porfiromycin);泼尼莫司汀(Prednimustine);盐酸丙卡巴肼(Procarbazine Hydrochloride);嘌呤霉素;盐酸嘌呤霉素;吡唑呋喃菌素(Pyrazofurin);利波腺苷(Riboprine);罗谷亚胺(Rogletimide);沙芬戈(Safingol);盐酸沙芬戈(Safingol Hydrochloride);司莫司汀;辛曲秦(Simtrazene);斯帕福斯特钠(SparfosateSodium);稀疏霉素(Sparsomycin);盐酸螺旋锗(Spirogermanium Hydrochloride);螺莫司汀(Spiromustine);螺铂(Spiroplatin);链黑菌素;链脲霉素;磺氯苯脲(Sulofenur);他利霉素(Talisomycin);紫杉酚(Taxol);替可加兰钠(Tecogalan Sodium);替加氟;盐酸替洛蒽醌(Teloxantrone Hydrochloride);替莫泊芬(Temoporfin);替尼泊苷;替罗昔隆(Teroxirone);睾内酯;硫咪嘌呤(Thiamiprine);硫鸟嘌呤(Thioguanine);塞替派(Thiotepa);噻唑呋林(Tiazofuirin);替拉扎明;盐酸拓扑替康;柠檬酸托瑞米芬;乙酸曲托龙(Trestolone Acetate);磷酸曲西立滨(Triciribine Phosphate);三甲曲沙;葡萄糖醛酸三甲曲沙;曲普瑞林;盐酸妥布氯唑(Tubulozole Hydrochloride);乌拉莫司汀(Uracil mustard);乌瑞替派(Uredepa);伐普肽(Vapreotide);维替泊芬;硫酸长春碱;硫酸长春新碱;长春地辛;硫酸长春地辛;硫酸长春匹定(Vinepidine Sulfate);硫酸长春甘酯(Vinglycinate Sulfate);硫酸长春罗辛(Vinleurosine Sulfate);酒石酸长春瑞滨(Vinorelbine Tartrate);硫酸长春罗定(Vinrosidine Sulfate);硫酸长春利定(Vinzolidine Sulfate);伏氯唑(Vorozole);折尼铂(Zeniplatin);净司他丁(Zinostatin);盐酸佐柔比星。附加抗肿瘤剂包括Goodman和Gilman的"ThePharmacological Basis of Therapeutics",第8版,1990,McGraw-Hill,Inc.(HealthProfessions Division)的第52章Antineoplastic Agents(Paul Calabresi和BruceA.Chabner)及其引言,1202-1263中公开的那些。
为了增强癌症治疗,本发明进一步考虑给予对象附加疗法,如放射疗法、化疗、光疗和光动力疗法、外科手术、营养疗法、消融疗法、联合放射疗法和化疗、臂疗法(brachiotherapy)、质子束疗法、免疫疗法、细胞疗法和光子束放射疗法。也考虑止痛药和其它治疗方案。
本文所用的术语“抗炎剂”是指预防或减轻炎性反应或通过减轻发炎症状,如发红、疼痛、热或肿而缓解炎症的试剂。
可与本发明的一些实施方案的EGR1靶向药物组合给药的抗炎药包括,但不限于阿氯芬酸;二丙酸阿氯米松(Alclometasone Dipropionate);丙缩阿尔孕酮(AlgestoneAcetonide);α淀粉酶;安西法尔(Amcinafal);安西非特(Amcinafide);氨芬酸钠(AmfenacSodium);盐酸氨普立糖(Amiprilose Hydrochloride);阿那白滞素;阿尼罗酸(Anirolac);阿尼扎芬(Anitrazafen);阿扎丙宗(Apazone);巴柳氮二钠;苄达酸;苯噁洛芬(Benoxaprofen);盐酸苄达明;菠萝蛋白酶;溴哌莫(Broperamole);布地奈德;卡布洛芬;环洛芬(Cicloprofen);辛喷他宗(Cintazone);克利洛芬(Cliprofen);丙酸氯倍他索;丁酸氯倍他松;氯吡酸(Clopirac);丙酸氯硫卡松(Cloticasone Propionate);醋酸三氟米松(Cormethasone Acetate);可托多松(Cortodoxone);地夫可特;地奈德;去羟米松;二丙酸地塞米松;双氯芬酸钾;双氯酚酸钠;双醋酸双氟拉松;二氟米酮钠;二氟尼柳;二氟泼尼酯(Difluprednate);双酞嗪酮(Diftalone);二甲亚砜;羟西奈德(Drocinonide);甲地松(Endrysone);恩莫单抗(Enlimomab);依诺立康钠(Enolicam Sodium);依匹唑;依托度酸;依托芬那酯;联苯乙酸(Felbinac);非那莫(Fenamole);芬布芬;芬氯酸(Fenclofenac);苯克洛酸(Fenclorac);苯吲柳酸(Fendosal);苯吡噁二酮(Fenpipalone);芬替酸(Fentiazac);夫拉扎酮(Flazalone);氟扎可特(Fluazacort);氟芬那酸;氟咪唑(Flumizole);醋酸氟尼缩松(Flunisolide Acetate);氟尼辛(Flunixin);氟尼辛葡甲胺(Flunixin Meglumine);氟考丁酯(Fluocortin Butyl);醋酸氟米龙;苯氟喹酮(Fluquazone);氟比洛芬;氟瑞托芬(Fluretofen);丙酸氟替卡松;呋喃洛芬(Furaprofen);呋罗布芬(Furobufen);哈西奈德;丙酸卤倍他索(Halobetasol Propionate);醋酸卤泼尼松(Halopredone Acetate);异丁芬酸(Ibufenac);布洛芬;布洛芬铝;布洛芬吡啶甲醇(Ibuprofen Piconol);伊洛达普(Ilonidap);吲哚美辛;吲哚美辛钠;吲哚布洛芬;吲哚克索(Indoxole);吲四唑(Intrazole);醋酸异氟泼尼松(Isoflupredone Acetate);伊索克酸(Isoxepac);伊索昔康;酮布洛芬(ketoprofen);盐酸洛非咪唑(LofemizoleHydrochloride);氯诺昔康;氯替泼诺碳酸乙酯(Loteprednol Etabonate);甲氯芬那酸钠(Meclofenamate Sodium);甲氯芬那酸;二丁酸甲氯松(Meclorisone Dibutyrate);甲芬那酸;美沙拉嗪;美西拉宗(Meseclazone);磺庚甲泼尼松(MethylprednisoloneSuleptanate);吗尼氟酯(Momiflumate);萘丁美酮;萘普生;萘普生钠;萘普索(Naproxol);尼马宗(Nimazone);奥沙拉嗪钠;肝蛋白(Orgotein);奥帕诺辛(Orpanoxin);奥沙普秦;羟基保泰松;盐酸瑞尼托林(Paranyline Hydrochloride);戊聚硫钠(Pentosan PolysulfateSodium);甘油保泰松钠(Phenbutazone Sodium Glycerate);吡非尼酮;吡罗昔康;肉桂酸吡罗昔康;吡罗昔康乙醇胺(Piroxicam Olamine);吡诺布洛芬(Pirprofen);泼娜扎特(Prednazate);普立非酮(Prifelone);普罗度酸(Prodolic Acid);普罗喹宗(Proquazone);普罗沙唑(Proxazole);柠檬酸普罗沙唑(Proxazole Citrate);利美索龙(Rimexolone);氯马扎利(Romazarit);水杨酸胆碱硫酸镁(Salcolex);沙那西定(Salnacedin);双水杨酯(Salsalate);血根氯铵(Sanguinarium Chloride);氯唑噁酮(Seclazone);丝美辛(Sermetacin);舒多昔康(Sudoxicam);舒林酸;舒洛芬;他美辛(Talmetacin);他尼氟酯(Talniflumate);他洛柳酯(Talosalate);特丁非隆(Tebufelone);替尼达普(Tenidap);替尼达普钠(Tenidap Sodium);替诺昔康;氧喹苯胺(Tesicam);苄叉异喹酮(Tesimide);四氢甲吲胺(Tetrydamine);硫平酸(Tiopinac);替可的松匹伐酯(Tixocortol Pivalate);托美丁;托美丁钠;三氯氟松(Triclonide);三氟氨酯(Triflumidate);齐多美辛(Zidometacin);佐美酸钠(Zomepirac Sodium)。
如果需要,本发明的一些实施方案的组合物(EGR1靶向药物和/或如上所述的任选抗癌或抗炎剂)可存在于包装或分配器,如FDA批准的药盒(kit)中,其可含有一个或多个含有活性成分的单位剂型。该包装可以例如包含金属或塑料箔,如泡罩包装。该包装或分配器可带有给药说明书。该包装或分配器也可带有管理药品制造、使用或销售的政府机构规定的形式的与容器相关的公告,该公告反映该机构对该组合物的形式或人用或兽用的批准。这样的公告可以例如是美国食品药品管理局批准用于处方药的标签或批准的产品插页。也可以制备包含在相容性药物载体中配制的本发明的制剂的组合物,其置于适当的容器中,并如上文进一步详述对指示病况的治疗进行标注说明。
定义:
本文所用的术语“大约”是指±10%。
术语“包含”、“包括”、“具有”和它们的同源词是指“包括但不限于”。
术语“由...构成”是指“包括并且限于”。
术语“基本由...构成”是指该组合物、方法或结构可包括附加成分、步骤和/或部分,但前提是该附加成分、步骤和/或部分不会实质上改变所要求保护的组合物、方法或结构的基本和新颖特征。
除非上下文清楚地作出相反的规定,本文所用的单数形式“一个”、“一种”和“该”包括复数对象。例如,术语“一种化合物”或“至少一种化合物”可包括多种化合物,包括其混合物。
在本申请通篇中,本发明的各种实施方案可以范围格式表示。应该理解的是,范围格式的描述仅为方便和简要起见并且不应被解释为对本发明的范围的刻板限制。相应地,范围的描述应该被认为具体公开所有可能的子范围以及在该范围内的独立数值。例如,如1至6之类的范围的描述应该被认为具体公开如1至3、1至4、1至5、2至4、2至6、3至6等的子范围,以及在该范围内的独立数值,例如1、2、3、4、5和6。无论该范围的幅度如何,这都适用。
每当在本文中指出数值范围时,其意在包括该指示范围内的所有列举的数值(分数或整数)。短语在第一指示数值和第二指示数值“之间”和“从”第一指示数值“至”第二指示数值在本文中可互换使用并且意在包括第一和第二指示数值和它们之间的所有分数和整数。
本文所用的术语“方法”是指实现给定任务的方式、手段、技术和程序,包括但不限于化学、药理学、生物、生物化学和医疗领域的从业人员已知的,或容易由已知方式、手段、技术和程序开发出的那些方式、手段、技术和程序。
本文所用的术语“胺”描述–NR'R"基团和–NR'-基团,其中R'和R"各自独立地为氢、烷基、环烷基、芳基,这些术语如下文定义。
该胺基团因此可以是伯胺,其中R'和R"都是氢,仲胺,其中R'是氢且R"是烷基、环烷基或芳基,或叔胺,其中R'和R"各自独立地为烷基、环烷基或芳基。
或者,R'和R”可以各自独立地为羟烷基、三卤烷基、环烷基、烯基、炔基、芳基、杂芳基、杂脂环族基团、胺、卤化物、磺酸酯基、亚砜、膦酸酯基、羟基、烷氧基、芳氧基、巯基、硫代烷氧基、硫代芳氧基、氰基、硝基、偶氮、磺酰胺、羰基、C-羧酸酯基、O-羧酸酯基、N-硫代氨基甲酸酯基、O-硫代氨基甲酸酯基、脲、硫脲、N-氨基甲酸酯基、O-氨基甲酸酯基、C-酰胺、N-酰胺、脒基、胍和肼。
当胺形成环的一部分(如在式I中那样)时,其取代基如本文中对式I所定义。
术语“烷基”描述包括直链和支链基团的饱和脂族烃。该烷基优选具有1至20个碳原子。每当在本文中规定数值范围,例如“1-20”时,其意味着该基团,在这种情况下是烷基,可含有1个碳原子、2个碳原子、3个碳原子,等等,直至并且包括20个碳原子。更优选地,该烷基是具有1至10个碳原子的中级烷基。最优选地,除非另行指明,该烷基是具有1至4个碳原子的低级烷基(C(1-4)烷基)。该烷基可以是取代或未取代的。取代的烷基可具有一个或多个取代基,由此各取代基可以独立地为例如羟烷基、三卤烷基、环烷基、烯基、炔基、芳基、杂芳基、杂脂环族基团、胺、卤化物、磺酸酯基、亚砜、膦酸酯基、羟基、烷氧基、芳氧基、巯基、硫代烷氧基、硫代芳氧基、氰基、硝基、偶氮、磺酰胺、C-羧酸酯基、O-羧酸酯基、N-硫代氨基甲酸酯基、O-硫代氨基甲酸酯基、脲、硫脲、N-氨基甲酸酯基、O-氨基甲酸酯基、C-酰胺、N-酰胺、脒基、胍和肼。
该烷基可以是端基(如这一术语在上文所定义),其中其连接到单个相邻原子上,或是连接基(如这一术语在上文所定义),其经由其链中的至少两个碳连接两个或更多个基团。当烷基是连接基时,其在本文中也被称作“亚烷基”或“亚烷基链”。
本文所用的烯烃和炔烃分别是含有一个或多个双键或三键的如本文中定义的烷基。
每当在本文中作为取代基描述烷基时,其可被如本文中所述的烯烃或炔烃替代。
术语“环烷基”描述全碳单环或稠环(即共享相邻碳原子对的环)基团,其中一个或多个环不具有完全共轭的π电子体系。实例包括但不限于,环己烷、金刚烷、降冰片基、异冰片基等。该环烷基可以是取代或未取代的。取代的环烷基可具有一个或多个取代基,其中各取代基可以独立地为例如羟烷基、三卤烷基、环烷基、烯基、炔基、芳基、杂芳基、杂脂环族基团、胺、卤化物、磺酸酯基、亚砜、膦酸酯基、羟基、烷氧基、芳氧基、巯基、硫代烷氧基、硫代芳氧基、氰基、硝基、偶氮、磺酰胺、C-羧酸酯基、O-羧酸酯基、N-硫代氨基甲酸酯基、O-硫代氨基甲酸酯基、脲、硫脲、N-氨基甲酸酯基、O-氨基甲酸酯基、C-酰胺、N-酰胺、脒基、胍和肼。该环烷基可以是端基(如这一短语在上文所定义),其中其连接到单个相邻原子上,或是连接基(如这一短语在上文所定义),在其两个或更多个位置连接两个或更多个基团。
术语“杂脂环族基团”描述在一个或多个环中具有一个或多个原子,如氮、氧和硫的单环或稠环基团。该环也可具有一个或多个双键。但是,该环不具有完全共轭的π电子体系。代表性实例是哌啶、哌嗪、四氢呋喃、四氢吡喃、吗啉基、噁唑烷(oxalidine)等。该杂脂环族基团可以是取代或未取代的。取代的杂脂环族基团可具有一个或多个取代基,其中各取代基可以独立地为例如羟烷基、三卤烷基、环烷基、烯基、炔基、芳基、杂芳基、杂脂环族基团、胺、卤化物、磺酸酯基、亚砜、膦酸酯基、羟基、烷氧基、芳氧基、巯基、硫代烷氧基、硫代芳氧基、氰基、硝基、偶氮、磺酰胺、C-羧酸酯基、O-羧酸酯基、N-硫代氨基甲酸酯基、O-硫代氨基甲酸酯基、脲、硫脲、O-氨基甲酸酯基、N-氨基甲酸酯基、C-酰胺、N-酰胺、脒基、胍和肼。该杂脂环族基团可以是端基(如这一短语在上文所定义),其中其连接到单个相邻原子上,或是连接基(如这一短语在上文所定义),在其两个或更多个位置连接两个或更多个基团。
术语“芳基”描述具有完全共轭的π电子体系的全碳单环或稠环多环(即共享相邻碳原子对的环)基团。该芳基可以是取代或未取代的。取代的芳基可具有一个或多个取代基,其中各取代基可以独立地为例如羟烷基、三卤烷基、环烷基、烯基、炔基、芳基、杂芳基、杂脂环族基团、胺、卤化物、磺酸酯基、亚砜、膦酸酯基、羟基、烷氧基、芳氧基、巯基、硫代烷氧基、硫代芳氧基、氰基、硝基、偶氮、磺酰胺、C-羧酸酯基、O-羧酸酯基、N-硫代氨基甲酸酯基、O-硫代氨基甲酸酯基、脲、硫脲、N-氨基甲酸酯基、O-氨基甲酸酯基、C-酰胺、N-酰胺、脒基、胍和肼。该芳基可以是端基(如这一术语在上文所定义),其中其连接到单个相邻原子上,或是连接基(如这一术语在上文所定义),在其两个或更多个位置连接两个或更多个基团。
术语“杂芳基”描述在一个或多个环中具有一个或多个原子,例如氮、氧和硫并另外具有完全共轭的π电子体系的单环或稠环(即共享相邻原子对的环)基团。杂芳基的实例非限制性地包括吡咯、呋喃、噻吩、咪唑、噁唑、噻唑、吡唑、吡啶、嘧啶、喹啉、异喹啉和嘌呤。该杂芳基可以是取代或未取代的。取代的杂芳基可具有一个或多个取代基,其中各取代基可以独立地为例如羟烷基、三卤烷基、环烷基、烯基、炔基、芳基、杂芳基、杂脂环族基团、胺、卤化物、磺酸酯基、亚砜、膦酸酯基、羟基、烷氧基、芳氧基、巯基、硫代烷氧基、硫代芳氧基、氰基、硝基、偶氮、磺酰胺、C-羧酸酯基、O-羧酸酯基、N-硫代氨基甲酸酯基、O-硫代氨基甲酸酯基、脲、硫脲、O-氨基甲酸酯基、N-氨基甲酸酯基、C-酰胺、N-酰胺、脒基、胍和肼。该杂芳基可以是端基(如这一短语在上文所定义),其中其连接到单个相邻原子上,或是连接基(如这一短语在上文所定义),在其两个或更多个位置连接两个或更多个基团。代表性实例是吡啶、吡咯、噁唑、吲哚、嘌呤等。
术语“卤化物”和“卤素”描述氟、氯、溴或碘。
术语“卤代烷基”描述被一个或多个卤化物进一步取代的如上定义的烷基。三卤烷基,如三卤甲基描述-CT3基团,其中各T是卤素。
术语“羟基”描述–OH基团。
术语“烷氧基”描述如本文定义的-O-烷基和-O-环烷基。
术语“芳氧基”描述如本文定义的-O-芳基和-O-杂芳基。
术语“巯基”描述-SH基团。
术语“硫代烷氧基”描述如本文定义的-S-烷基和-S-环烷基。
术语“硫代芳氧基”描述如本文定义的-S-芳基和-S-杂芳基。
“羟烷基”在本文中也被称作“醇”,并描述被羟基取代的如本文定义的烷基。
术语“氰基”描述-C≡N基团。
术语“硝基”描述-NO2基团。
术语“硫酸酯基”描述–O–S(=O)2–OR'端基(如这一术语在上文所定义)或–O-S(=O)2-O–连接基(如这些短语在上文所定义),其中R'如上文所定义。
术语“硫代硫酸酯基”描述–O–S(=S)(=O)–OR'端基或–O–S(=S)(=O)–O–连接基(如这些短语在上文所定义),其中R'如上文所定义。
术语“亚硫酸酯基”描述–O–S(=O)–O–R'端基或-O-S(=O)-O–基团连接基(如这些短语在上文所定义),其中R'如上文所定义。
术语“硫代亚硫酸酯基”描述–O–S(=S)–O–R'端基或–O–S(=S)–O–基团连接基(如这些短语在上文所定义),其中R'如上文所定义。
术语“亚磺酸酯基”描述–S(=O)-OR'端基或–S(=O)–O–基团连接基(如这些短语在上文所定义),其中R'如上文所定义。
术语“亚砜”或“亚磺酰基”描述–S(=O)R'端基或–S(=O)–连接基(如这些短语在上文所定义),其中R'如上文所定义。
术语“磺酸酯基”描述–S(=O)2-R'端基或–S(=O)2-连接基(如这些短语在上文所定义),其中R'如本文所定义。
术语“S-磺酰胺”描述–S(=O)2-NR'R"端基或–S(=O)2-NR'–连接基(如这些短语在上文所定义),其中R'和R'’如本文所定义。
术语“N-磺酰胺”描述R'S(=O)2–NR"–端基或-S(=O)2-NR'–连接基(如这些短语在上文所定义),其中R'和R'’如本文所定义。
本文所用的术语“羰基”或“碳酸酯基”描述-C(=O)-R'端基或-C(=O)-连接基(如这些短语在上文所定义),其中R'如本文所定义。
本文所用的术语“硫代羰基”描述-C(=S)-R'端基或-C(=S)-连接基(如这些短语在上文所定义),其中R'如本文所定义。
本文所用的术语“氧代”描述(=O)基团,其中氧原子通过双键连接到所示位置的原子(例如碳原子)上。
本文所用的术语“硫代(thiooxo)”描述(=S)基团,其中硫原子通过双键连接到所示位置的原子(例如碳原子)上。
术语“肟”描述=N–OH端基或=N-O-连接基(如这些短语在上文所定义)。
术语“酰基卤”描述–(C=O)R””基团,其中R””是如上文定义的卤化物。
术语“偶氮”或“重氮”描述-N=NR'端基或-N=N-连接基(如这些短语在上文所定义),其中R'如上文定义。
术语“过氧”描述–O–OR'端基或–O–O-连接基(如这些短语在上文所定义),其中R'如上文定义。
本文所用的术语“羧酸酯基”包括C-羧酸酯基和O-羧酸酯基。
术语“C-羧酸酯基”描述-C(=O)-OR'端基或-C(=O)-O-连接基(如这些短语在上文所定义),其中R'如本文所定义。
术语“O-羧酸酯基”描述-OC(=O)R'端基或-OC(=O)-连接基(如这些短语在上文所定义),其中R'如本文所定义。
羧酸酯基可以是直链或环状的。当是环状时,R'和碳原子在C-羧酸酯基中连接在一起以形成环,这一基团也被称作内酯。或者,R'和O在O-羧酸酯基中连接在一起以形成环。环状羧酸酯基可充当连接基,例如当形成的环中的原子连接到另一基团上时。
本文所用的术语“硫代羧酸酯基”包括C-硫代羧酸酯基和O-硫代羧酸酯基。
术语“C-硫代羧酸酯基”描述-C(=S)-OR'端基或-C(=S)-O-连接基(如这些短语在上文所定义),其中R'如本文所定义。
术语“O-硫代羧酸酯基”描述-OC(=S)R'端基或-OC(=S)-连接基(如这些短语在上文所定义),其中R'如本文所定义。
硫代羧酸酯基可以是直链或环状的。当是环状时,R'和碳原子在C-硫代羧酸酯基中连接在一起以形成环,这一基团也被称作硫代内酯。或者,R'和O在O-硫代羧酸酯基中连接在一起以形成环。环状硫代羧酸酯基可充当连接基,例如当形成的环中的原子连接到另一基团上时。
本文所用的术语“氨基甲酸酯基”包括N-氨基甲酸酯基和O-氨基甲酸酯基。
术语“N-氨基甲酸酯基”描述R"OC(=O)-NR'-端基或-OC(=O)-NR'-连接基(如这些短语在上文所定义),其中R'和R"如本文所定义。
术语“O-氨基甲酸酯基”描述-OC(=O)-NR'R"端基或-OC(=O)-NR'-连接基(如这些短语在上文所定义),其中R'和R"如本文所定义。
氨基甲酸酯基可以是直链或环状的。当是环状时,R'和碳原子在O-氨基甲酸酯基中连接在一起以形成环。或者,R'和O在N-氨基甲酸酯基中连接在一起以形成环。环状氨基甲酸酯基可充当连接基,例如当形成的环中的原子连接到另一基团上时。
本文所用的术语“氨基甲酸酯基”包括N-氨基甲酸酯基和O-氨基甲酸酯基。
本文所用的术语“硫代氨基甲酸酯基”包括N-硫代氨基甲酸酯基和O-硫代氨基甲酸酯基。
术语“O-硫代氨基甲酸酯基”描述-OC(=S)-NR'R"端基或-OC(=S)-NR'-连接基(如这些短语在上文所定义),其中R'和R"如本文所定义。
术语“N-硫代氨基甲酸酯基”描述R"OC(=S)NR'-端基或-OC(=S)NR'-连接基(如这些短语在上文所定义),其中R'和R"如本文所定义。
如本文中对氨基甲酸酯所描述,硫代氨基甲酸酯可以是线性或环状的。
本文所用的术语“二硫代氨基甲酸酯基”包括S-二硫代氨基甲酸酯基和N-二硫代氨基甲酸酯基。
术语“S-二硫代氨基甲酸酯基”描述-SC(=S)-NR'R"端基或-SC(=S)NR'-连接基(如这些短语在上文所定义),其中R'和R"如本文所定义。
术语“N-二硫代氨基甲酸酯基”描述R"SC(=S)NR'-端基或-SC(=S)NR'-连接基(如这些短语在上文所定义),其中R'和R"如本文所定义。
在本文中也被称作“脲基”的术语“脲”描述-NR'C(=O)-NR"R”'端基或-NR'C(=O)-NR"-连接基(如这些短语在上文所定义),其中R'和R"如本文所定义并且R”'如本文对R'和R”所定义。
在本文中也被称作“硫脲基”的术语“硫脲”描述-NR'-C(=S)-NR"R”'端基或-NR'-C(=S)-NR"-连接基,其中R'、R"和R”'如本文所定义。
本文所用的术语“酰胺”包括C-酰胺和N-酰胺。
术语“C-酰胺”描述-C(=O)-NR'R"端基或-C(=O)-NR'-连接基(如这些短语在上文所定义),其中R'和R"如本文所定义。
术语“N-酰胺”描述R'C(=O)-NR"-端基或R'C(=O)-N-连接基(如这些短语在上文所定义),其中R'和R"如本文所定义。
术语“脒基”描述R'R"NC(=N)-端基或–R'NC(=N)-连接基(如这些短语在上文所定义),其中R'和R"如本文所定义。
术语“胍”描述–R'NC(=N)-NR"R”'端基或–R'NC(=N)-NR"-连接基(如这些短语在上文所定义),其中R'、R”和R”'如本文所定义。
术语“肼”描述-NR'-NR"R”'端基或-NR'-NR"-连接基(如这些短语在上文所定义),其中R'、R"和R”'如本文所定义。
本文所用的术语“酰肼”描述-C(=O)-NR'-NR"R”'端基或-C(=O)-NR'-NR"-连接基(如这些短语在上文所定义),其中R'、R"和R”'如本文所定义。
本文所用的术语“硫代酰肼”描述-C(=S)-NR'-NR"R”'端基或-C(=S)-NR'-NR"-连接基(如这些短语在上文所定义),其中R'、R"和R”'如本文所定义。
要认识到,为清楚起见在单独的实施方案中描述的本发明的某些特征也可以组合提供在单个实施方案中。反过来说,为简要起见在单个实施方案中描述的本发明的各种特征也可以分开或以任何合适的亚组合或酌情在本发明的任何其它所述实施方案中提供。各种实施方案中描述的某些特征不应被视为这些实施方案的基本特征,除非该实施方案没有这些要素无法运作。
如上文描述和如下列权利要求部分中要求保护的本发明的各种实施方案和方面在下列实施例中找到实验支持。
实施例
现在参考下列实施例,它们与上述说明书一起以非限制性方式举例说明本发明。
通常,本文所用的术语和本发明中所用的实验室程序包括分子、生物化学、微生物学和重组DNA技术。在文献中充分解释了这样的技术。参见例如"Molecular Cloning:Alaboratory Manual"Sambrook等人,(1989);"Current Protocols in MolecularBiology"第I-III卷Ausubel,R.M.编辑(1994);Ausubel等人,"Current Protocols inMolecular Biology",John Wiley and Sons,Baltimore,Maryland(1989);Perbal,"APractical Guide to Molecular Cloning",John Wiley&Sons,New York(1988);Watson等人,"Recombinant DNA",Scientific American Books,New York;Birren等人(编辑)"Genome Analysis:ALaboratoryManual Series",第1-4卷,Cold Spring HarborLaboratory Press,New York(1998);如美国专利4,666,828;4,683,202;4,801,531;5,192,659和5,272,057中阐述的方法;"Cell Biology:A Laboratory Handbook",第I-III卷Cellis,J.E.编辑(1994);"Current Protocols in Immunology"第I-III卷Coligan J.E.编辑(1994);Stites等人(eds),"Basic and Clinical Immunology"(第8版),Appleton&Lange,Norwalk,CT(1994);Mishell和Shiigi(编辑),"Selected Methods in CellularImmunology",W.H.Freeman and Co.,New York(1980);可用的免疫测定法广泛描述在专利和科学文献中,参见例如美国专利3,791,932;3,839,153;3,850,752;3,850,578;3,853,987;3,867,517;3,879,262;3,901,654;3,935,074;3,984,533;3,996,345;4,034,074;4,098,876;4,879,219;5,011,771和5,281,521;"Oligonucleotide Synthesis"Gait,M.J.,ed.(1984);“Nucleic Acid Hybridization"Hames,B.D.,和Higgins S.J.编辑(1985);"Transcription and Translation"Hames,B.D.和Higgins S.J.编辑(1984);"Animal CellCulture"Freshneym,R.I.编辑(1986);"Immobilized Cells and Enzymes"IRL Press,(1986);"A Practical Guide to Molecular Cloning"Perbal,B.,(1984)和"Methods inEnzymology"第1-317卷,Academic Press;"PCR Protocols:A Guide to Methods andApplications",Academic Press,San Diego,CA(1990);Marshak等人,"Strategies forProtein Purification and Characterization-A Laboratory Course Manual"CSHLPress(1996);所有这些如同在本文中充分阐述那样经此引用并入本文。在本文各处提供其它一般参考文献。其中的程序被认为是本领域中公知的并为了读者的方便提供。其中包含的所有信息经此引用并入本文。
材料和实验程序
细胞培养:
将HeLa细胞在含有10%FCS、1%L-谷氨酰胺和1%青霉素和链霉素的DMEM 4.5g/l葡萄糖培养基(Biological Industries)中培养并在37℃和5%CO2下生长。
将TERC-转化的成纤维细胞用含有人端粒酶基因的pBABE-H2AGFP构建子(construct)转化,用High Glucose DMEM、10%FCS、L-谷氨酰胺和Pen-Strep(所有细胞培养试剂来自Biological Industries,Israel)培养。每2-3天更换培养基。细胞在第2-3代使用。
从成人皮肤中分离原代成纤维细胞并在High Glucose DMEM、10%胎牛血清、L-谷氨酰胺和Pen-Strep中生长。每2-3天更换培养基。细胞在第2-3代使用。
注意,当用CaCx和ApD(NCI,MA USA)培养细胞时,它们在仅含0.1%FCS的适当培养基中生长。
动物:
将Balb/c小鼠(Harlan Laboratories Ltd,Jerusalem,Israel),9周龄,饲养在无病原体的动物设施中。动物护理和研究程序已获机构委员会批准用于动物。使用咪喹莫特5%(Perrigo,Israel)作为小鼠上背部的局部处理。小鼠一周5次腹腔注射DMSO或分别7.5-22.5mg/kg ApDx和CaCx(NCI)。使用10%DMSO/脂褐质作为赋形剂对照物。
嵌合体小鼠:
使用2–3月龄的SCID小鼠生成携带人类银屑病皮肤的嵌合体小鼠。将动物饲养在无病原体的动物设施中。通过衍生自如之前描述的银屑病患者的自然杀伤/T细胞的皮内注射,在移植到小鼠中的正常人类皮肤中诱发银屑病样表型[Gilhar A等人J InvestDermatol(2011)131:118-124]。
光学显微术和免疫组织化学:
将来自皮肤活检的甲醛固定的5-μm石蜡包埋切片去石蜡并用3%H2O2/甲醇在室温下处理15分钟,在微波炉中在柠檬酸盐缓冲液中在压力蒸煮器中加热25分钟并用单克隆抗-Ki67抗体(Thermo Scientific)在室温下染色1小时。在用磷酸盐缓冲盐水(PBS)洗涤3次(每次10分钟)后,使用ABC技术(Zymed Laboratories,South San Francisco,CA)将抗体成像并且用苏木精复染载玻片。
表皮厚度被定义为颗粒层与基底膜之间的距离并对于各活检物在10个随机选择的位置使用NIS-Elements BR 3.2软件(Nikon,NY USA)测量。获取图像并在该软件中通过选择如上定义的上和下边界手动测量图像。以微米为单位测量距离。
定量逆转录PCR(qRT-PCR):
使用RNA提取试剂盒(Roche Diagnostics,Mahheim,Germany)从细胞培养物中提取RNA。由500ng总RNA使用Verso cDNA试剂盒(Thermo Fisher Scientific,Waltham,MA,USA)合成cDNA。使用StepOnePlusTMReal-Time PCR System(Applied Biosystems,FosterCity,CA,USA)中的Fast SYBR Green Master Mix用(下)表1中所列的基因特异性内含子交叉寡核苷酸对进行cDNA PCR扩增。为了量化,使用在相同qRT-PCR运行中扩增的连续稀释cDNA获得标准曲线。测量扩增产物的熔融温度(Tm)以证实反应条件的特异性。循环条件如下:95℃10分钟、95℃10秒、62℃15秒和72℃25秒,总共40个循环。将各样品一式三份进行分析。将靶基因的mRNA表达水平归一化至GAPDH。结果基于靶的量,归一化至内参照(endogenous reference)(IACTB)并相对于校准品,如通过2-ΔΔCT计算的。将所有样品一式三份运行。作为mRNA相对单位表示靶基因的表达水平。
表1:寡核苷酸序列
基因名称 | 序列 | SEQ ID号 |
SAMD9F | 5’-CGAGCAAGGTCCTTCCATAGTG-3’ | 1 |
SAMD9R | 5’-CCGATGACCTCACAGCTCAAG-3’ | 2 |
EGR1F | 5’-GGGCAGTCGAGTGGTTTGG-3’ | 3 |
EGR1R | 5’-TTGCCGACAGGATGCAGAAGGA-3’ | 4 |
。
质粒和表达构建子:
将如上所述克隆到pGL3中的SAMD9启动子片段[Hershkovitz,D.等人(2011)JInvest Dermatol 131:662-9]用KpnI和XhoI消化并亚克隆到pGL4.17[luc2/Neo](Promega)中。表达载体pGL4.17编码荧光素酶报告基因luc2(Photinuspyralis)并含有新霉素耐药性的哺乳动物选择标记。对于瞬时转染,使用lipofectamine 2000(Invitrogen,Carlsbad,CA)根据制造商的说明书将SAMD9启动子-荧光素酶构建子转染到HeLa细胞中。
在新霉素选择下生成稳定表达该构建子的HeLa细胞系。简言之,将含有在TSS上游跨越585bp的SAMD9启动子片段的pGL4.17和无pGL4.17载体转染到HeLa细胞中。在转染后48小时,将标准培养基换成含有600μg/ml G418的培养基(Sigma-Aldrich),将细胞保持在G418选择下,并且大约每2-3天更换选择性培养基。在2次传代后,分离稳定细胞的集落,扩大并冻结以供进一步使用。
双荧光素酶报告基因测定:
通过将20微升Promega Lysis Buffer(PLB)(Promega)添加到各样品中并培养15分钟,提取细胞蛋白质。将细胞裂解液在96孔白色平板(Greiner Bio-One,UnitedKingdom)中进行分析,其中将100微升荧光素酶测定试剂II(LAR II)(Promega)添加到各样品中。使用Infinite M200多模式酶标仪(Tecan Ltd,Switzerland)确定发光。在初始读数后,将100微升Stop&GloR Reagent(Promega)分配到受试孔中并测试Renilla荧光素酶水平。在将荧光素酶水平归一化至Renilla水平后完成该测定。
用于识别SAMD9上调剂的高通量筛选:
通过机器人系统将受试药物以10μM的浓度分配到含有表达携带有效连接到荧光素酶基因上的585bp SAMD9启动子片段的pGL4.17报告基因构建子或无pGL4.17荧光素酶构建子(Promega cat.no.E6721)的9000个细胞/孔的96孔板中。在24小时后除去培养基并对细胞施以如上所述的Steady-Glo荧光素酶裂解-底物溶液测定(Promega)。用Tecan(Tecan)Freedom 150(Robotic&MCA liquid Handling System)进行液体操作并用机器人集成Tecan M1000读数器进行荧光素酶读数。
实施例1
SAMD9表达的诱导剂的高通量筛选
首先使用HeLa细胞中的荧光素酶报告基因测定分析SAMD9启动子活性。将在SAMD9预测转录起始位点(TSS)上游跨越585bp的片段(SEQ ID NO:5)克隆到pGL4中并用pRL-TKRenilla荧光素酶(hRluc)共转染到HeLa细胞中。在转染后四十八(48)小时,通过测量荧光素酶活性确定启动子活性。在存在和不存在之前被确定为SAMD9表达的强诱导剂[Hershkovitz,D.等人(2011),见上文]的IFN-γ(10ng/ml)的情况下检测构建子。IFN-γ显著诱导SAMD9启动子活性(图1A)。随后生成在-585bp SAMD9启动子片段的调节下结构性地表达萤火虫荧光素酶基因的稳定HeLa细胞系,发现其有力地响应IFN-γ(图1B)。
然后使用这一细胞系机器人筛选获自National Cancer Institute DiversitySet III和Oncology Drugs Set III小分子库的总共1496种化合物。在初始筛选中发现诱导荧光素酶活性的85种化合物中,观察到31种可再现地诱导报告HeLa细胞系中的SAMD9启动子活性超过两倍(见下表2)。
实施例2
CaCx和ApDx对人细胞培养物中的SAMD9表达的影响
然后仔细检查这31种分子诱导细胞培养物中的SAMD9表达的潜在能力。数据显示在下表2中。发现两种化合物,6H-吡啶并[4,3-b]咔唑-1-甲酰胺,5,11-二甲基-,单盐酸盐(CaCx)和10-正-丙基-1,3-二氯-7-氨基-吩噻嗪-5,5-二氧化物(ApDx)显著诱导HeLa细胞、TERC-转化的成纤维细胞和原代成纤维细胞中的SAMD9表达(图1C)。发现CaCx和ApDx介导的SAMD9上调是剂量和时间依赖性的(图2A-B)。注意,各化合物表现出不同的最佳剂量和时间曲线。
这两种化合物都显著下调原代成纤维细胞中的EGR1表达,尽管在不同时间点(图3)。
实施例3
CaCx和ApDx的全身给药对小鼠中的咪喹莫特诱发的银屑病样皮炎的影响
CaCx和ApDx下调EGR1(皮肤中的炎性反应的主要介体)表达的能力表明这些化合物可充当抗炎药。在使用咪喹莫特诱发银屑病样皮炎的小鼠模型[如Tortola,L.等人(2012)J Clin Invest 122,3965-76中之前描述]中测试这一假设。
用咪喹莫特局部处理Balb/c小鼠并每周5次腹腔注射赋形剂、22.5mg/kg CaCx或7.5mg/kgApDx。
在5天后,从经处理的皮肤获得活检物并用苏木精和曙红以及Ki67染色(图4A-F),作为细胞增殖的替代标志。用任一化合物处理导致增殖指标中的表皮厚度降低(图5A)但不影响炎性浸润。对任一化合物没有观察到明显毒性。
定量PCR证实在CaCx-和ApDx-处理的皮肤中,EGR1(图5B)和IL-33(皮肤中的一种重要的炎症标记物,图5C)RNA水平都显著降低。
实施例4
嵌合体小鼠体内实验
为了评估本发明的一些实施方案的化合物(ApDx和CaCx)的潜在治疗作用,将这两种化合物全身给药至(腹腔注射)携带人类银屑病皮肤的嵌合体小鼠。简言之,将2–3月龄的SCID小鼠饲养在无病原体的动物设施中。通过衍生自如之前描述的银屑病患者的自然杀伤/T细胞的皮内注射,在移植到小鼠中的正常人类皮肤中诱发银屑病样表型[Gilhar A等人J Invest Dermatol(2011)131:118-124]。在自然杀伤/T细胞注射后2周(在人类皮肤移植后6周),经小鼠每周5次腹腔注射。如下处理四组小鼠:一组小鼠每周5次注射赋形剂;第二组小鼠每周5次注射ApDx(5mg/kg);第三组小鼠每周5次注射CaCx(15mg/kg);第四组小鼠用每周5次施加在移植物上的地塞米松(DEX)乳膏处理,作为阳性对照(DEX预计在这一模型中减弱炎症)。各组包括5只小鼠,该处理进行总共10天。从这四组小鼠收获移植物,将其石蜡包埋,苏木精和曙红(H&E)染色,分析并对临床和组织学银屑病样表型的平均改善评分。
如图6中图示说明,结果表明这两种化合物(ApDx和CaCx)都导致银屑病样表型的显著临床和组织学减弱(ApDx p<0.0001、CaCx p<0.05)。此外,作为细胞增殖的替代标志,在10天后从CaCx-或ApDx-处理的皮肤获得并用苏木精和曙红以及Ki67染色的活检物表明携带人类银屑病皮肤的嵌合体小鼠中的表皮厚度和角质形成细胞增殖的显著降低(图7A-F和图8)。对任一化合物没有观察到明显毒性。此外,定量PCR证实在CaCx-处理的皮肤中EGR1RNA水平显著降低(图9)。
综合而言,这些结果表明EGR1靶向疗法可充当过度增殖性皮肤炎性疾病的现行疗法的替代或补充。
尽管已结合其具体实施方案描述了本发明,但许多替代方案、修改和变动显然是本领域技术人员显而易见的。因此其意在涵盖落在所附权利要求书的精神和宽范围内的所有这样的替代方案、修改和变动。
本说明书中提到的所有出版物、专利和专利申请全文经此引用并入本说明书,如同各出版物、专利或专利申请明确和逐一被指示为经此引用并入本文。此外,本申请中引用或指出任何参考文献不应被视为承认这样的参考文献可充当本发明的现有技术。在使用章节标题的情况下,它们不应被视为必要限制。
Claims (7)
2.权利要求1的用途,其中R5和R8各自为甲基。
3.权利要求1或2的用途,其中所述皮肤炎症与慢性炎性疾病相关联。
4.权利要求1或2的用途,其中所述皮肤炎症与急性炎性疾病相关联。
5.权利要求1或2的用途,其中所述皮肤炎症选自特应性皮炎、接触性皮炎、疱疹样皮炎、泛发性表皮脱落性皮炎、脂溢性皮炎、牛皮癣、药疹、多形性红斑、结节性红斑、环状肉芽肿、毒葛皮炎、毒橡树皮炎、中毒性表皮坏死松解症、痤疮和红斑痤疮。
6.权利要求1或2的用途,其中所述药物进一步包含抗炎剂。
7.权利要求1或2的用途,其中治疗所述炎症进一步包含施用抗炎剂。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201562153087P | 2015-04-27 | 2015-04-27 | |
US62/153,087 | 2015-04-27 | ||
PCT/IL2016/050439 WO2016174674A1 (en) | 2015-04-27 | 2016-04-26 | Egr1 targeting molecules for the treatment of inflammatory and hyperproliferative conditions |
Publications (2)
Publication Number | Publication Date |
---|---|
CN108135863A CN108135863A (zh) | 2018-06-08 |
CN108135863B true CN108135863B (zh) | 2021-07-27 |
Family
ID=55971160
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201680037911.9A Active CN108135863B (zh) | 2015-04-27 | 2016-04-26 | 用于治疗炎性和过度增殖性病况的egr1靶向分子 |
Country Status (8)
Country | Link |
---|---|
US (1) | US20180289728A1 (zh) |
EP (1) | EP3288547B1 (zh) |
CN (1) | CN108135863B (zh) |
AU (1) | AU2016255725B2 (zh) |
CA (1) | CA2986202C (zh) |
ES (1) | ES2951653T3 (zh) |
IL (1) | IL255290B2 (zh) |
WO (1) | WO2016174674A1 (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108516929B (zh) * | 2018-01-24 | 2021-06-18 | 温州医科大学 | 一种2-亚-(3-甲氧基-4-羟基)-苄基-1-茚酮类似物及应用 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0502668A1 (en) * | 1991-03-05 | 1992-09-09 | Btg International Limited | Imidazoacridines and their antineoplastic use |
WO2006002082A2 (en) * | 2004-06-16 | 2006-01-05 | Jack Arbiser | Carbazole formulations for the treatment of psoriasis and angiogenesis |
WO2009017795A1 (en) * | 2007-08-02 | 2009-02-05 | Xanthus Pharmaceuticals, Inc. | Indazole compounds for treating inflammatory disorders, demyelinating disorders and cancers |
CN104224785A (zh) * | 2014-09-04 | 2014-12-24 | 南京标科生物科技有限公司 | 5-羟基去甲山柚柑碱在制备抗肿瘤药物中的应用 |
Family Cites Families (35)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NL154600B (nl) | 1971-02-10 | 1977-09-15 | Organon Nv | Werkwijze voor het aantonen en bepalen van specifiek bindende eiwitten en hun corresponderende bindbare stoffen. |
US3655699A (en) * | 1970-03-02 | 1972-04-11 | Pfizer | Analogues of lapachol as antitumor agents |
NL154598B (nl) | 1970-11-10 | 1977-09-15 | Organon Nv | Werkwijze voor het aantonen en bepalen van laagmoleculire verbindingen en van eiwitten die deze verbindingen specifiek kunnen binden, alsmede testverpakking. |
NL154599B (nl) | 1970-12-28 | 1977-09-15 | Organon Nv | Werkwijze voor het aantonen en bepalen van specifiek bindende eiwitten en hun corresponderende bindbare stoffen, alsmede testverpakking. |
US3901654A (en) | 1971-06-21 | 1975-08-26 | Biological Developments | Receptor assays of biologically active compounds employing biologically specific receptors |
US3853987A (en) | 1971-09-01 | 1974-12-10 | W Dreyer | Immunological reagent and radioimmuno assay |
US3867517A (en) | 1971-12-21 | 1975-02-18 | Abbott Lab | Direct radioimmunoassay for antigens and their antibodies |
NL171930C (nl) | 1972-05-11 | 1983-06-01 | Akzo Nv | Werkwijze voor het aantonen en bepalen van haptenen, alsmede testverpakkingen. |
US3850578A (en) | 1973-03-12 | 1974-11-26 | H Mcconnell | Process for assaying for biologically active molecules |
US3935074A (en) | 1973-12-17 | 1976-01-27 | Syva Company | Antibody steric hindrance immunoassay with two antibodies |
US3996345A (en) | 1974-08-12 | 1976-12-07 | Syva Company | Fluorescence quenching with immunological pairs in immunoassays |
US4034074A (en) | 1974-09-19 | 1977-07-05 | The Board Of Trustees Of Leland Stanford Junior University | Universal reagent 2-site immunoradiometric assay using labelled anti (IgG) |
US3984533A (en) | 1975-11-13 | 1976-10-05 | General Electric Company | Electrophoretic method of detecting antigen-antibody reaction |
US4098876A (en) | 1976-10-26 | 1978-07-04 | Corning Glass Works | Reverse sandwich immunoassay |
US4879219A (en) | 1980-09-19 | 1989-11-07 | General Hospital Corporation | Immunoassay utilizing monoclonal high affinity IgM antibodies |
US5011771A (en) | 1984-04-12 | 1991-04-30 | The General Hospital Corporation | Multiepitopic immunometric assay |
US4666828A (en) | 1984-08-15 | 1987-05-19 | The General Hospital Corporation | Test for Huntington's disease |
US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
US4801531A (en) | 1985-04-17 | 1989-01-31 | Biotechnology Research Partners, Ltd. | Apo AI/CIII genomic polymorphisms predictive of atherosclerosis |
US5272057A (en) | 1988-10-14 | 1993-12-21 | Georgetown University | Method of detecting a predisposition to cancer by the use of restriction fragment length polymorphism of the gene for human poly (ADP-ribose) polymerase |
US5192659A (en) | 1989-08-25 | 1993-03-09 | Genetype Ag | Intron sequence analysis method for detection of adjacent and remote locus alleles as haplotypes |
US5102883A (en) * | 1989-10-31 | 1992-04-07 | Du Pont Merck Pharmaceutical Company | Pyrimidine biosynthesis inhibitors useful as immunosuppressive agents |
US5281521A (en) | 1992-07-20 | 1994-01-25 | The Trustees Of The University Of Pennsylvania | Modified avidin-biotin technique |
US5667487A (en) | 1993-04-07 | 1997-09-16 | Henley; Julian L. | Ionosonic drug delivery apparatus |
PT1233770E (pt) * | 1999-12-03 | 2008-04-24 | Univ California At San Diego | Compostos de fosfonato |
US7056929B2 (en) * | 2001-07-25 | 2006-06-06 | Les Laboratoires Servier | Benzo[b]pyrano[3,2-h]acridin-7-one compounds |
AU2004223866A1 (en) * | 2003-03-24 | 2004-10-07 | Luitpold Pharmaceuticals, Inc. | Xanthones, thioxanthones and acridinones as DNA-PK inhibitors |
FR2856687B1 (fr) * | 2003-06-25 | 2005-09-16 | Servier Lab | Nouveaux derives de benzo[a]pyrano[3,2-h]acridin-7-one, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
WO2006094207A2 (en) * | 2005-03-03 | 2006-09-08 | St. Jude Children's Research Hospital | Substituted phenoxazines and acridones as inhibitors of akt |
WO2007092436A2 (en) * | 2006-02-08 | 2007-08-16 | Xanthus Pharmaceuticals, Inc. | Compounds for treating inflammatory disorders, demyelinating disorders and cancers |
WO2008016661A2 (en) * | 2006-08-02 | 2008-02-07 | Xanthus Pharmaceuticals, Inc. | Morpholino compounds for treating inflammatory and demyelinating diseases and cancers |
WO2012048265A2 (en) | 2010-10-08 | 2012-04-12 | The Broad Institute Of Mit And Harvard | Methods of treating inflammation |
WO2014011540A1 (en) * | 2012-07-09 | 2014-01-16 | Emory University | Bone morphogenetic protein pathway activation, compositions for ossification, and methods related thereto |
US11198724B2 (en) * | 2013-03-14 | 2021-12-14 | The Regents Of The University Of Michigan | Treatment of staphylococcal disorders |
EP3125891A4 (en) * | 2014-03-31 | 2017-08-09 | Mirx Pharmaceuticals, LLC | Novel hdmx inhibitors and their use for cancer treatment |
-
2016
- 2016-04-26 CN CN201680037911.9A patent/CN108135863B/zh active Active
- 2016-04-26 US US15/569,407 patent/US20180289728A1/en active Pending
- 2016-04-26 WO PCT/IL2016/050439 patent/WO2016174674A1/en active Application Filing
- 2016-04-26 AU AU2016255725A patent/AU2016255725B2/en active Active
- 2016-04-26 CA CA2986202A patent/CA2986202C/en active Active
- 2016-04-26 ES ES16722951T patent/ES2951653T3/es active Active
- 2016-04-26 EP EP16722951.7A patent/EP3288547B1/en active Active
- 2016-04-26 IL IL255290A patent/IL255290B2/en unknown
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0502668A1 (en) * | 1991-03-05 | 1992-09-09 | Btg International Limited | Imidazoacridines and their antineoplastic use |
WO2006002082A2 (en) * | 2004-06-16 | 2006-01-05 | Jack Arbiser | Carbazole formulations for the treatment of psoriasis and angiogenesis |
WO2009017795A1 (en) * | 2007-08-02 | 2009-02-05 | Xanthus Pharmaceuticals, Inc. | Indazole compounds for treating inflammatory disorders, demyelinating disorders and cancers |
CN104224785A (zh) * | 2014-09-04 | 2014-12-24 | 南京标科生物科技有限公司 | 5-羟基去甲山柚柑碱在制备抗肿瘤药物中的应用 |
Also Published As
Publication number | Publication date |
---|---|
IL255290A0 (en) | 2017-12-31 |
CA2986202C (en) | 2023-08-22 |
EP3288547A1 (en) | 2018-03-07 |
EP3288547B1 (en) | 2023-06-07 |
AU2016255725B2 (en) | 2021-09-23 |
WO2016174674A1 (en) | 2016-11-03 |
AU2016255725A1 (en) | 2017-11-30 |
CA2986202A1 (en) | 2016-11-03 |
ES2951653T3 (es) | 2023-10-24 |
IL255290B1 (en) | 2023-09-01 |
CN108135863A (zh) | 2018-06-08 |
US20180289728A1 (en) | 2018-10-11 |
IL255290B2 (en) | 2024-01-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Yadav et al. | JAK/STAT3 pathway is involved in survival of neurons in response to insulin-like growth factor and negatively regulated by suppressor of cytokine signaling-3 | |
Seizer et al. | Extracellular cyclophilin A activates platelets via EMMPRIN (CD147) and PI3K/Akt signaling, which promotes platelet adhesion and thrombus formation in vitro and in vivo | |
Johns et al. | Hypoxia-inducible factor 1α is a critical downstream mediator for hypoxia-induced mitogenic factor (FIZZ1/RELMα)–induced pulmonary hypertension | |
Fetter et al. | Selective janus kinase 1 inhibition is a promising therapeutic approach for lupus erythematosus skin lesions | |
Joly et al. | β4 integrin and laminin 5 are aberrantly expressed in polycystic kidney disease: role in increased cell adhesion and migration | |
Yeh et al. | Lercanidipine and labedipinedilol-A attenuate lipopolysaccharide/interferon-γ-induced inflammation in rat vascular smooth muscle cells through inhibition of HMGB1 release and MMP-2, 9 activities | |
US11274132B2 (en) | Combined preparations of PKM2 modulators and HMGB1 | |
US20210309620A1 (en) | Compositions and methods for treating and/or preventing cell or tissue necrosis specifically targeting cathepsin c and/or cela1 and/or cela3a and/or structurally related enzymes thereto | |
US20200061076A1 (en) | Methods of treating leukodystrophies | |
Han et al. | Retracted: Effects of FOSL1 silencing on osteosarcoma cell proliferation, invasion and migration through the ERK/AP‐1 signaling pathway | |
CN109843339A (zh) | 影响肿瘤杀伤的双重靶向构建体 | |
Zhou et al. | Wnt5a promotes cortical neuron survival by inhibiting cell-cycle activation | |
He et al. | MiR-29b-3p aggravates cardiac hypoxia/reoxygenation injury via targeting PTX3 | |
Wu et al. | lncRNA Neat1 regulates neuronal dysfunction post-sepsis via stabilization of hemoglobin subunit beta | |
CN108135863B (zh) | 用于治疗炎性和过度增殖性病况的egr1靶向分子 | |
Gu et al. | Ibrutinib exacerbates bleomycin-induced pulmonary fibrosis via promoting inflammation | |
Shavit-Stein et al. | A novel compound targeting protease receptor 1 activators for the treatment of glioblastoma | |
Iwasaki et al. | Regulation of cellular senescence in type 2 diabetes mellitus: From mechanisms to clinical applications | |
Li et al. | Calycosin attenuates the inflammatory damage of microglia induced by oxygen and glucose deprivation through the HMGB1/TLR4/NF-κB signaling pathway: calycosin attenuates OGD/R damage in microglia | |
Pham et al. | Essential role of Lyn in fibrosis | |
Hu et al. | Circular RNA PUM1 performs as a competing endogenous RNA of microRNA-340-5p to mediate DEAD-box helicase 5 to mitigate cerebral ischemia-reperfusion injury | |
US20170253881A1 (en) | Compositions and methods of selectively inhibiting irp1 and treating inflammation | |
Bryan | The Role of Bardet-Biedl Syndrome Protein 1 in the Pancreatic Beta Cell | |
AU2022243540A9 (en) | Compositions and articles comprising an adnf polypeptide | |
Leviny | A walk through the valley of cell death |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |