RU2472511C2 - Композиции и способы применения форболовых эфиров - Google Patents

Info

Publication number

RU2472511C2

RU2472511C2 RU2009132345/15A RU2009132345A RU2472511C2 RU 2472511 C2 RU2472511 C2 RU 2472511C2 RU 2009132345/15 A RU2009132345/15 A RU 2009132345/15A RU 2009132345 A RU2009132345 A RU 2009132345A RU 2472511 C2 RU2472511 C2 RU 2472511C2

Authority

RU

Russia

Prior art keywords

treatment

tpa

hiv

symptoms

acetate

Prior art date

2007-01-31

Links

• Espacenet
• Global Dossier
• Discuss

• 239000000203 mixture Substances 0.000 title claims abstract description 133
• 238000000034 method Methods 0.000 title claims abstract description 112
• 239000002644 phorbol ester Substances 0.000 title description 83
• 150000004633 phorbol derivatives Chemical class 0.000 title description 46
• 238000011282 treatment Methods 0.000 claims abstract description 211
• 208000024891 symptom Diseases 0.000 claims abstract description 132
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 113
• 201000010099 disease Diseases 0.000 claims abstract description 108
• PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 claims abstract description 65
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 56
• 208000031886 HIV Infections Diseases 0.000 claims abstract description 45
• 239000003814 drug Substances 0.000 claims abstract description 43
• 230000001965 increasing effect Effects 0.000 claims abstract description 43
• 208000037357 HIV infectious disease Diseases 0.000 claims abstract description 42
• 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims abstract description 42
• 150000003839 salts Chemical class 0.000 claims abstract description 34
• 239000012453 solvate Substances 0.000 claims abstract description 24
• 102000004127 Cytokines Human genes 0.000 claims abstract description 18
• 108090000695 Cytokines Proteins 0.000 claims abstract description 18
• 230000006907 apoptotic process Effects 0.000 claims abstract description 13
• 230000002265 prevention Effects 0.000 claims abstract description 12
• 230000014509 gene expression Effects 0.000 claims abstract description 11
• 230000001939 inductive effect Effects 0.000 claims abstract description 7
• -1 fl konazola Chemical compound 0.000 claims description 46
• 230000001613 neoplastic effect Effects 0.000 claims description 41
• 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 claims description 39
• 229940124597 therapeutic agent Drugs 0.000 claims description 25
• 206010012735 Diarrhoea Diseases 0.000 claims description 23
• 206010037660 Pyrexia Diseases 0.000 claims description 22
• 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 claims description 17
• 229960003957 dexamethasone Drugs 0.000 claims description 17
• 206010025323 Lymphomas Diseases 0.000 claims description 16
• 208000016261 weight loss Diseases 0.000 claims description 16
• 230000004580 weight loss Effects 0.000 claims description 16
• 230000006378 damage Effects 0.000 claims description 15
• 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 claims description 14
• 208000003265 stomatitis Diseases 0.000 claims description 13
• FXEDIXLHKQINFP-UHFFFAOYSA-N 12-O-tetradecanoylphorbol-13-acetate Natural products CCCCCCCCCCCCCC(=O)OC1CC2(O)C(C=C(CO)CC3(O)C2C=C(C)C3=O)C4C(C)(C)C14OC(=O)C FXEDIXLHKQINFP-UHFFFAOYSA-N 0.000 claims description 12
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 11
• 208000007502 anemia Diseases 0.000 claims description 11
• 239000011777 magnesium Substances 0.000 claims description 11
• 229910052749 magnesium Inorganic materials 0.000 claims description 11
• 201000008827 tuberculosis Diseases 0.000 claims description 11
• 241000701022 Cytomegalovirus Species 0.000 claims description 10
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 10
• 210000003169 central nervous system Anatomy 0.000 claims description 10
• 108010002350 Interleukin-2 Proteins 0.000 claims description 9
• 102000000588 Interleukin-2 Human genes 0.000 claims description 9
• 230000004596 appetite loss Effects 0.000 claims description 9
• 208000015181 infectious disease Diseases 0.000 claims description 9
• 208000008953 Cryptosporidiosis Diseases 0.000 claims description 8
• 206010011502 Cryptosporidiosis infection Diseases 0.000 claims description 8
• MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound 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 claims description 8
• 208000019017 loss of appetite Diseases 0.000 claims description 8
• 235000021266 loss of appetite Nutrition 0.000 claims description 8
• 210000000214 mouth Anatomy 0.000 claims description 8
• 230000001713 cholinergic effect Effects 0.000 claims description 7
• 230000003247 decreasing effect Effects 0.000 claims description 7
• 229960004679 doxorubicin Drugs 0.000 claims description 7
• 239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims description 7
• YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 claims description 7
• 229960001860 salicylate Drugs 0.000 claims description 7
• 208000011580 syndromic disease Diseases 0.000 claims description 7
• 208000009889 Herpes Simplex Diseases 0.000 claims description 6
• 238000010521 absorption reaction Methods 0.000 claims description 6
• 239000003112 inhibitor Substances 0.000 claims description 6
• 206010043554 thrombocytopenia Diseases 0.000 claims description 6
• 201000002909 Aspergillosis Diseases 0.000 claims description 5
• 208000036641 Aspergillus infections Diseases 0.000 claims description 5
• 208000011691 Burkitt lymphomas Diseases 0.000 claims description 5
• 241000222122 Candida albicans Species 0.000 claims description 5
• 206010007134 Candida infections Diseases 0.000 claims description 5
• 241000223205 Coccidioides immitis Species 0.000 claims description 5
• 208000005794 Hairy Leukoplakia Diseases 0.000 claims description 5
• 241000282414 Homo sapiens Species 0.000 claims description 5
• 208000029082 Pelvic Inflammatory Disease Diseases 0.000 claims description 5
• 241000233872 Pneumocystis carinii Species 0.000 claims description 5
• 206010035664 Pneumonia Diseases 0.000 claims description 5
• 206010039438 Salmonella Infections Diseases 0.000 claims description 5
• 201000005485 Toxoplasmosis Diseases 0.000 claims description 5
• 208000025865 Ulcer Diseases 0.000 claims description 5
• 230000003213 activating effect Effects 0.000 claims description 5
• 229960005310 aldesleukin Drugs 0.000 claims description 5
• 108700025316 aldesleukin Proteins 0.000 claims description 5
• 201000003984 candidiasis Diseases 0.000 claims description 5
• 201000003486 coccidioidomycosis Diseases 0.000 claims description 5
• 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 claims description 5
• 229960005420 etoposide Drugs 0.000 claims description 5
• 208000006454 hepatitis Diseases 0.000 claims description 5
• 231100000283 hepatitis Toxicity 0.000 claims description 5
• 208000008588 molluscum contagiosum Diseases 0.000 claims description 5
• 208000002040 neurosyphilis Diseases 0.000 claims description 5
• 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 5
• 206010039447 salmonellosis Diseases 0.000 claims description 5
• 208000006379 syphilis Diseases 0.000 claims description 5
• 231100000397 ulcer Toxicity 0.000 claims description 5
• VHVPQPYKVGDNFY-DFMJLFEVSA-N 2-[(2r)-butan-2-yl]-4-[4-[4-[4-[[(2r,4s)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one Chemical compound O=C1N([C@H](C)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@@H]3O[C@](CN4N=CN=C4)(OC3)C=3C(=CC(Cl)=CC=3)Cl)=CC=2)C=C1 VHVPQPYKVGDNFY-DFMJLFEVSA-N 0.000 claims description 4
• APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 claims description 4
• 208000004597 Bacillary angiomatosis Diseases 0.000 claims description 4
• JVTAAEKCZFNVCJ-UWTATZPHSA-N D-lactic acid Chemical compound C[C@@H](O)C(O)=O JVTAAEKCZFNVCJ-UWTATZPHSA-N 0.000 claims description 4
• CYQFCXCEBYINGO-DLBZAZTESA-N Dronabinol Natural products C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@H]21 CYQFCXCEBYINGO-DLBZAZTESA-N 0.000 claims description 4
• 201000002563 Histoplasmosis Diseases 0.000 claims description 4
• 108060003951 Immunoglobulin Proteins 0.000 claims description 4
• 108010050904 Interferons Proteins 0.000 claims description 4
• 102000014150 Interferons Human genes 0.000 claims description 4
• 206010023076 Isosporiasis Diseases 0.000 claims description 4
• 208000007766 Kaposi sarcoma Diseases 0.000 claims description 4
• 208000008771 Lymphadenopathy Diseases 0.000 claims description 4
• 201000000090 Microsporidiosis Diseases 0.000 claims description 4
• 229940122313 Nucleoside reverse transcriptase inhibitor Drugs 0.000 claims description 4
• 229930012538 Paclitaxel Natural products 0.000 claims description 4
• IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 4
• CYQFCXCEBYINGO-UHFFFAOYSA-N THC Natural products C1=C(C)CCC2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3C21 CYQFCXCEBYINGO-UHFFFAOYSA-N 0.000 claims description 4
• WPVFJKSGQUFQAP-GKAPJAKFSA-N Valcyte Chemical compound N1C(N)=NC(=O)C2=C1N(COC(CO)COC(=O)[C@@H](N)C(C)C)C=N2 WPVFJKSGQUFQAP-GKAPJAKFSA-N 0.000 claims description 4
• ZWBTYMGEBZUQTK-PVLSIAFMSA-N [(7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-2,15,17,32-tetrahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-1'-(2-methylpropyl)-6,23-dioxospiro[8,33-dioxa-24,27,29-triazapentacyclo[23.6.1.14,7.05,31.026,30]tritriaconta-1(32),2,4,9,19,21,24,26,30-nonaene-28,4'-piperidine]-13-yl] acetate Chemical compound CO[C@H]1\C=C\O[C@@]2(C)Oc3c(C2=O)c2c4NC5(CCN(CC(C)C)CC5)N=c4c(=NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)c(O)c2c(O)c3C ZWBTYMGEBZUQTK-PVLSIAFMSA-N 0.000 claims description 4
• 229960004150 aciclovir Drugs 0.000 claims description 4
• WOZSCQDILHKSGG-UHFFFAOYSA-N adefovir depivoxil Chemical compound N1=CN=C2N(CCOCP(=O)(OCOC(=O)C(C)(C)C)OCOC(=O)C(C)(C)C)C=NC2=C1N WOZSCQDILHKSGG-UHFFFAOYSA-N 0.000 claims description 4
• 229960003205 adefovir dipivoxil Drugs 0.000 claims description 4
• APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 claims description 4
• 229960003942 amphotericin b Drugs 0.000 claims description 4
• MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 claims description 4
• 229960004099 azithromycin Drugs 0.000 claims description 4
• 229960002626 clarithromycin Drugs 0.000 claims description 4
• AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 claims description 4
• 201000008167 cystoisosporiasis Diseases 0.000 claims description 4
• CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 claims description 4
• 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 claims description 4
• 229960004242 dronabinol Drugs 0.000 claims description 4
• 230000004927 fusion Effects 0.000 claims description 4
• 229960002963 ganciclovir Drugs 0.000 claims description 4
• 102000018358 immunoglobulin Human genes 0.000 claims description 4
• 229940072221 immunoglobulins Drugs 0.000 claims description 4
• 229940124524 integrase inhibitor Drugs 0.000 claims description 4
• 239000002850 integrase inhibitor Substances 0.000 claims description 4
• 229940079322 interferon Drugs 0.000 claims description 4
• 229960003350 isoniazid Drugs 0.000 claims description 4
• QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 claims description 4
• 229960004130 itraconazole Drugs 0.000 claims description 4
• 229960001786 megestrol Drugs 0.000 claims description 4
• 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 claims description 4
• 230000003641 microbiacidal effect Effects 0.000 claims description 4
• 229940124561 microbicide Drugs 0.000 claims description 4
• 229940042402 non-nucleoside reverse transcriptase inhibitor Drugs 0.000 claims description 4
• 239000002726 nonnucleoside reverse transcriptase inhibitor Substances 0.000 claims description 4
• 229960001592 paclitaxel Drugs 0.000 claims description 4
• XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 claims description 4
• XDRYMKDFEDOLFX-UHFFFAOYSA-N pentamidine Chemical compound C1=CC(C(=N)N)=CC=C1OCCCCCOC1=CC=C(C(N)=N)C=C1 XDRYMKDFEDOLFX-UHFFFAOYSA-N 0.000 claims description 4
• 229960004448 pentamidine Drugs 0.000 claims description 4
• 238000011321 prophylaxis Methods 0.000 claims description 4
• 229960000329 ribavirin Drugs 0.000 claims description 4
• HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 4
• 229960000885 rifabutin Drugs 0.000 claims description 4
• 229960001225 rifampicin Drugs 0.000 claims description 4
• 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 claims description 4
• 229960003604 testosterone Drugs 0.000 claims description 4
• 229960002149 valganciclovir Drugs 0.000 claims description 4
• 102000002265 Human Growth Hormone Human genes 0.000 claims description 3
• 108010000521 Human Growth Hormone Proteins 0.000 claims description 3
• 239000000854 Human Growth Hormone Substances 0.000 claims description 3
• XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 claims description 3
• 230000000798 anti-retroviral effect Effects 0.000 claims description 3
• 229940000425 combination drug Drugs 0.000 claims description 3
• 229960004532 somatropin Drugs 0.000 claims description 3
• 230000009885 systemic effect Effects 0.000 claims description 3
• 238000011269 treatment regimen Methods 0.000 claims description 3
• 241000186367 Mycobacterium avium Species 0.000 claims description 2
• 208000035269 cancer or benign tumor Diseases 0.000 claims description 2
• 206010036807 progressive multifocal leukoencephalopathy Diseases 0.000 claims description 2
• 241001337994 Cryptococcus <scale insect> Species 0.000 claims 1
• 201000009906 Meningitis Diseases 0.000 claims 1
• MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 claims 1
• 229960000980 entecavir Drugs 0.000 claims 1
• YXPVEXCTPGULBZ-WQYNNSOESA-N entecavir hydrate Chemical compound O.C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)C1=C YXPVEXCTPGULBZ-WQYNNSOESA-N 0.000 claims 1
• 230000003203 everyday effect Effects 0.000 claims 1
• IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 claims 1
• OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 claims 1
• JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 claims 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 claims 1
• 229960001099 trimetrexate Drugs 0.000 claims 1
• 230000000120 cytopathologic effect Effects 0.000 abstract description 43
• 230000000694 effects Effects 0.000 abstract description 35
• 230000004913 activation Effects 0.000 abstract description 8
• 239000000126 substance Substances 0.000 abstract description 6
• 241000124008 Mammalia Species 0.000 abstract description 4
• PHEDXBVPIONUQT-UHFFFAOYSA-N Cocarcinogen A1 Natural products CCCCCCCCCCCCCC(=O)OC1C(C)C2(O)C3C=C(C)C(=O)C3(O)CC(CO)=CC2C2C1(OC(C)=O)C2(C)C PHEDXBVPIONUQT-UHFFFAOYSA-N 0.000 description 178
• 150000001875 compounds Chemical class 0.000 description 85
• 208000030507 AIDS Diseases 0.000 description 83
• 241000725303 Human immunodeficiency virus Species 0.000 description 83
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 42
• 210000004027 cell Anatomy 0.000 description 38
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 37
• 210000000265 leukocyte Anatomy 0.000 description 31
• 238000002560 therapeutic procedure Methods 0.000 description 31
• NQDJXKOVJZTUJA-UHFFFAOYSA-N nevirapine Chemical compound C12=NC=CC=C2C(=O)NC=2C(C)=CC=NC=2N1C1CC1 NQDJXKOVJZTUJA-UHFFFAOYSA-N 0.000 description 26
• 230000001225 therapeutic effect Effects 0.000 description 25
• 210000004369 blood Anatomy 0.000 description 24
• 239000008280 blood Substances 0.000 description 24
• 230000003612 virological effect Effects 0.000 description 24
• 201000011510 cancer Diseases 0.000 description 23
• 239000003795 chemical substances by application Substances 0.000 description 23
• 150000002148 esters Chemical class 0.000 description 23
• 238000009472 formulation Methods 0.000 description 22
• 230000003211 malignant effect Effects 0.000 description 22
• 235000019789 appetite Nutrition 0.000 description 20
• 230000036528 appetite Effects 0.000 description 19
• 238000001802 infusion Methods 0.000 description 19
• 239000000651 prodrug Substances 0.000 description 18
• 229940002612 prodrug Drugs 0.000 description 18
• 210000001772 blood platelet Anatomy 0.000 description 17
• 206010016256 fatigue Diseases 0.000 description 16
• 230000000840 anti-viral effect Effects 0.000 description 15
• 230000036760 body temperature Effects 0.000 description 15
• 230000006698 induction Effects 0.000 description 15
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 14
• 230000007423 decrease Effects 0.000 description 13
• 208000002173 dizziness Diseases 0.000 description 13
• 210000000987 immune system Anatomy 0.000 description 13
• 229960000689 nevirapine Drugs 0.000 description 13
• 230000004044 response Effects 0.000 description 13
• 229960002555 zidovudine Drugs 0.000 description 13
• HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 13
• BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 description 12
• 102000003945 NF-kappa B Human genes 0.000 description 12
• 108010057466 NF-kappa B Proteins 0.000 description 12
• 229940079593 drug Drugs 0.000 description 12
• 230000001976 improved effect Effects 0.000 description 12
• 230000006872 improvement Effects 0.000 description 12
• 208000032839 leukemia Diseases 0.000 description 12
• 239000007787 solid Substances 0.000 description 12
• 206010019233 Headaches Diseases 0.000 description 11
• 208000032843 Hemorrhage Diseases 0.000 description 11
• 230000000973 chemotherapeutic effect Effects 0.000 description 11
• 231100000869 headache Toxicity 0.000 description 11
• 229910052739 hydrogen Inorganic materials 0.000 description 11
• 239000001257 hydrogen Substances 0.000 description 11
• 208000001388 Opportunistic Infections Diseases 0.000 description 10
• 125000003342 alkenyl group Chemical group 0.000 description 10
• 208000015322 bone marrow disease Diseases 0.000 description 10
• 230000008859 change Effects 0.000 description 10
• 210000003743 erythrocyte Anatomy 0.000 description 10
• 208000014951 hematologic disease Diseases 0.000 description 10
• 210000002700 urine Anatomy 0.000 description 10
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
• 230000037396 body weight Effects 0.000 description 9
• 239000000047 product Substances 0.000 description 9
• 230000000306 recurrent effect Effects 0.000 description 9
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 8
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 8
• 206010011224 Cough Diseases 0.000 description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
• NUQJULCGNZMBEF-UHFFFAOYSA-N Prostratin Natural products COC(=O)C12CC(C)C3(O)C(C=C(CO)CC4(O)C3C=C(C)C4=O)C1C2(C)C NUQJULCGNZMBEF-UHFFFAOYSA-N 0.000 description 8
• 241000700605 Viruses Species 0.000 description 8
• 125000000217 alkyl group Chemical group 0.000 description 8
• 239000003443 antiviral agent Substances 0.000 description 8
• 230000000740 bleeding effect Effects 0.000 description 8
• 229940091250 magnesium supplement Drugs 0.000 description 8
• 210000001167 myeloblast Anatomy 0.000 description 8
• 210000005259 peripheral blood Anatomy 0.000 description 8
• 239000011886 peripheral blood Substances 0.000 description 8
• 230000026731 phosphorylation Effects 0.000 description 8
• 238000006366 phosphorylation reaction Methods 0.000 description 8
• 239000011780 sodium chloride Substances 0.000 description 8
• 239000000243 solution Substances 0.000 description 8
• 238000012360 testing method Methods 0.000 description 8
• 102000001554 Hemoglobins Human genes 0.000 description 7
• 108010054147 Hemoglobins Proteins 0.000 description 7
• 208000017604 Hodgkin disease Diseases 0.000 description 7
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 7
• 238000004458 analytical method Methods 0.000 description 7
• 239000002246 antineoplastic agent Substances 0.000 description 7
• 230000015572 biosynthetic process Effects 0.000 description 7
• 238000004820 blood count Methods 0.000 description 7
• VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 7
• 238000001990 intravenous administration Methods 0.000 description 7
• 210000001165 lymph node Anatomy 0.000 description 7
• 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 6
• 208000000059 Dyspnea Diseases 0.000 description 6
• 206010013975 Dyspnoeas Diseases 0.000 description 6
• XPOQHMRABVBWPR-UHFFFAOYSA-N Efavirenz Natural products O1C(=O)NC2=CC=C(Cl)C=C2C1(C(F)(F)F)C#CC1CC1 XPOQHMRABVBWPR-UHFFFAOYSA-N 0.000 description 6
• XQSPYNMVSIKCOC-NTSWFWBYSA-N Emtricitabine Chemical compound C1=C(F)C(N)=NC(=O)N1[C@H]1O[C@@H](CO)SC1 XQSPYNMVSIKCOC-NTSWFWBYSA-N 0.000 description 6
• 206010018852 Haematoma Diseases 0.000 description 6
• 210000001744 T-lymphocyte Anatomy 0.000 description 6
• 208000027418 Wounds and injury Diseases 0.000 description 6
• 230000000259 anti-tumor effect Effects 0.000 description 6
• 238000002512 chemotherapy Methods 0.000 description 6
• WHBIGIKBNXZKFE-UHFFFAOYSA-N delavirdine Chemical compound CC(C)NC1=CC=CN=C1N1CCN(C(=O)C=2NC3=CC=C(NS(C)(=O)=O)C=C3C=2)CC1 WHBIGIKBNXZKFE-UHFFFAOYSA-N 0.000 description 6
• 239000002552 dosage form Substances 0.000 description 6
• 229960003804 efavirenz Drugs 0.000 description 6
• XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 description 6
• 229960000366 emtricitabine Drugs 0.000 description 6
• 208000014674 injury Diseases 0.000 description 6
• 229910052740 iodine Inorganic materials 0.000 description 6
• 230000004060 metabolic process Effects 0.000 description 6
• 230000027939 micturition Effects 0.000 description 6
• 230000000069 prophylactic effect Effects 0.000 description 6
• BOJKFRKNLSCGHY-HXGSDTCMSA-N prostratin Chemical compound C1=C(CO)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)C[C@@]3(OC(C)=O)C(C)(C)[C@H]3[C@@H]21 BOJKFRKNLSCGHY-HXGSDTCMSA-N 0.000 description 6
• 230000008961 swelling Effects 0.000 description 6
• 229960004556 tenofovir Drugs 0.000 description 6
• VCMJCVGFSROFHV-WZGZYPNHSA-N tenofovir disoproxil fumarate Chemical compound OC(=O)\C=C\C(O)=O.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VCMJCVGFSROFHV-WZGZYPNHSA-N 0.000 description 6
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 6
• 241000699670 Mus sp. Species 0.000 description 5
• 102000003923 Protein Kinase C Human genes 0.000 description 5
• 108090000315 Protein Kinase C Proteins 0.000 description 5
• 230000002411 adverse Effects 0.000 description 5
• 239000002259 anti human immunodeficiency virus agent Substances 0.000 description 5
• 238000011225 antiretroviral therapy Methods 0.000 description 5
• 238000009534 blood test Methods 0.000 description 5
• 230000001472 cytotoxic effect Effects 0.000 description 5
• 208000035475 disorder Diseases 0.000 description 5
• 238000007911 parenteral administration Methods 0.000 description 5
• 108090000623 proteins and genes Proteins 0.000 description 5
• 208000013220 shortness of breath Diseases 0.000 description 5
• 230000019491 signal transduction Effects 0.000 description 5
• 238000007920 subcutaneous administration Methods 0.000 description 5
• 230000004393 visual impairment Effects 0.000 description 5
• HJCUTNIGJHJGCF-UHFFFAOYSA-N 9,10-dihydroacridine Chemical compound C1=CC=C2CC3=CC=CC=C3NC2=C1 HJCUTNIGJHJGCF-UHFFFAOYSA-N 0.000 description 4
• 241000196324 Embryophyta Species 0.000 description 4
• 208000002250 Hematologic Neoplasms Diseases 0.000 description 4
• 208000021519 Hodgkin lymphoma Diseases 0.000 description 4
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 4
• 241000282412 Homo Species 0.000 description 4
• 102000043136 MAP kinase family Human genes 0.000 description 4
• 108091054455 MAP kinase family Proteins 0.000 description 4
• 201000003793 Myelodysplastic syndrome Diseases 0.000 description 4
• 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 4
• 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 4
• 208000003251 Pruritus Diseases 0.000 description 4
• XNKLLVCARDGLGL-JGVFFNPUSA-N Stavudine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1C=C[C@@H](CO)O1 XNKLLVCARDGLGL-JGVFFNPUSA-N 0.000 description 4
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 4
• 206010047571 Visual impairment Diseases 0.000 description 4
• 230000008901 benefit Effects 0.000 description 4
• 210000000988 bone and bone Anatomy 0.000 description 4
• 210000001185 bone marrow Anatomy 0.000 description 4
• 239000000872 buffer Substances 0.000 description 4
• 239000000460 chlorine Substances 0.000 description 4
• 231100000433 cytotoxic Toxicity 0.000 description 4
• 229940127089 cytotoxic agent Drugs 0.000 description 4
• 238000002474 experimental method Methods 0.000 description 4
• 238000000684 flow cytometry Methods 0.000 description 4
• 150000004677 hydrates Chemical class 0.000 description 4
• 238000002347 injection Methods 0.000 description 4
• 239000007924 injection Substances 0.000 description 4
• 230000007803 itching Effects 0.000 description 4
• 229960001627 lamivudine Drugs 0.000 description 4
• JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 4
• 238000012423 maintenance Methods 0.000 description 4
• 238000005259 measurement Methods 0.000 description 4
• 210000000440 neutrophil Anatomy 0.000 description 4
• 231100000957 no side effect Toxicity 0.000 description 4
• 239000000546 pharmaceutical excipient Substances 0.000 description 4
• 230000000750 progressive effect Effects 0.000 description 4
• 102000004169 proteins and genes Human genes 0.000 description 4
• 238000001959 radiotherapy Methods 0.000 description 4
• 230000009467 reduction Effects 0.000 description 4
• 238000001356 surgical procedure Methods 0.000 description 4
• 230000004083 survival effect Effects 0.000 description 4
• 238000013268 sustained release Methods 0.000 description 4
• 239000012730 sustained-release form Substances 0.000 description 4
• 208000029257 vision disease Diseases 0.000 description 4
• NIDRYBLTWYFCFV-FMTVUPSXSA-N (+)-calanolide A Chemical compound C1=CC(C)(C)OC2=C1C(O[C@H](C)[C@@H](C)[C@@H]1O)=C1C1=C2C(CCC)=CC(=O)O1 NIDRYBLTWYFCFV-FMTVUPSXSA-N 0.000 description 3
• QGVLYPPODPLXMB-UBTYZVCOSA-N (1aR,1bS,4aR,7aS,7bS,8R,9R,9aS)-4a,7b,9,9a-tetrahydroxy-3-(hydroxymethyl)-1,1,6,8-tetramethyl-1,1a,1b,4,4a,7a,7b,8,9,9a-decahydro-5H-cyclopropa[3,4]benzo[1,2-e]azulen-5-one Chemical compound C1=C(CO)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](O)[C@@]3(O)C(C)(C)[C@H]3[C@@H]21 QGVLYPPODPLXMB-UBTYZVCOSA-N 0.000 description 3
• CNPVJJQCETWNEU-CYFREDJKSA-N (4,6-dimethyl-5-pyrimidinyl)-[4-[(3S)-4-[(1R)-2-methoxy-1-[4-(trifluoromethyl)phenyl]ethyl]-3-methyl-1-piperazinyl]-4-methyl-1-piperidinyl]methanone Chemical compound N([C@@H](COC)C=1C=CC(=CC=1)C(F)(F)F)([C@H](C1)C)CCN1C(CC1)(C)CCN1C(=O)C1=C(C)N=CN=C1C CNPVJJQCETWNEU-CYFREDJKSA-N 0.000 description 3
• DBPMWRYLTBNCCE-UHFFFAOYSA-N 1-(4-benzoylpiperazin-1-yl)-2-(4,7-dimethoxy-1h-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione Chemical compound C1=2C(OC)=CN=C(OC)C=2NC=C1C(=O)C(=O)N(CC1)CCN1C(=O)C1=CC=CC=C1 DBPMWRYLTBNCCE-UHFFFAOYSA-N 0.000 description 3
• OKGPFTLYBPQBIX-CQSZACIVSA-N 1-[(2r)-4-benzoyl-2-methylpiperazin-1-yl]-2-(4-methoxy-1h-pyrrolo[2,3-b]pyridin-3-yl)ethane-1,2-dione Chemical compound C1=2C(OC)=CC=NC=2NC=C1C(=O)C(=O)N([C@@H](C1)C)CCN1C(=O)C1=CC=CC=C1 OKGPFTLYBPQBIX-CQSZACIVSA-N 0.000 description 3
• WLAMNBDJUVNPJU-UHFFFAOYSA-N 2-methylbutyric acid Chemical compound CCC(C)C(O)=O WLAMNBDJUVNPJU-UHFFFAOYSA-N 0.000 description 3
• GWNOTCOIYUNTQP-FQLXRVMXSA-N 4-[4-[[(3r)-1-butyl-3-[(r)-cyclohexyl(hydroxy)methyl]-2,5-dioxo-1,4,9-triazaspiro[5.5]undecan-9-yl]methyl]phenoxy]benzoic acid Chemical compound N([C@@H](C(=O)N1CCCC)[C@H](O)C2CCCCC2)C(=O)C1(CC1)CCN1CC(C=C1)=CC=C1OC1=CC=C(C(O)=O)C=C1 GWNOTCOIYUNTQP-FQLXRVMXSA-N 0.000 description 3
• LHCOVOKZWQYODM-CPEOKENHSA-N 4-amino-1-[(2r,5s)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]pyrimidin-2-one;1-[(2r,4s,5s)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1.O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 LHCOVOKZWQYODM-CPEOKENHSA-N 0.000 description 3
• VERWQPYQDXWOGT-LVJNJWHOSA-N 4-amino-5-fluoro-1-[(2r,5s)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]pyrimidin-2-one;[[(2r)-1-(6-aminopurin-9-yl)propan-2-yl]oxymethyl-(propan-2-yloxycarbonyloxymethoxy)phosphoryl]oxymethyl propan-2-yl carbonate;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C1=C(F)C(N)=NC(=O)N1[C@H]1O[C@@H](CO)SC1.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VERWQPYQDXWOGT-LVJNJWHOSA-N 0.000 description 3
• STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 3
• WVLHHLRVNDMIAR-IBGZPJMESA-N AMD 070 Chemical compound C1CCC2=CC=CN=C2[C@H]1N(CCCCN)CC1=NC2=CC=CC=C2N1 WVLHHLRVNDMIAR-IBGZPJMESA-N 0.000 description 3
• 206010059313 Anogenital warts Diseases 0.000 description 3
• AXRYRYVKAWYZBR-UHFFFAOYSA-N Atazanavir Natural products C=1C=C(C=2N=CC=CC=2)C=CC=1CN(NC(=O)C(NC(=O)OC)C(C)(C)C)CC(O)C(NC(=O)C(NC(=O)OC)C(C)(C)C)CC1=CC=CC=C1 AXRYRYVKAWYZBR-UHFFFAOYSA-N 0.000 description 3
• 108010019625 Atazanavir Sulfate Proteins 0.000 description 3
• 208000019838 Blood disease Diseases 0.000 description 3
• QAGYKUNXZHXKMR-UHFFFAOYSA-N CPD000469186 Natural products CC1=C(O)C=CC=C1C(=O)NC(C(O)CN1C(CC2CCCCC2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-UHFFFAOYSA-N 0.000 description 3
• NIDRYBLTWYFCFV-IUUKEHGRSA-N Calanolide A Natural products C1=CC(C)(C)OC2=C1C(O[C@H](C)[C@H](C)[C@@H]1O)=C1C1=C2C(CCC)=CC(=O)O1 NIDRYBLTWYFCFV-IUUKEHGRSA-N 0.000 description 3
• 206010008342 Cervix carcinoma Diseases 0.000 description 3
• 206010008479 Chest Pain Diseases 0.000 description 3
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
• 208000000907 Condylomata Acuminata Diseases 0.000 description 3
• 244000168525 Croton tiglium Species 0.000 description 3
• 208000006081 Cryptococcal meningitis Diseases 0.000 description 3
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 3
• 238000002965 ELISA Methods 0.000 description 3
• 108010032976 Enfuvirtide Proteins 0.000 description 3
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 206010018999 Haemorrhage subcutaneous Diseases 0.000 description 3
• 208000007514 Herpes zoster Diseases 0.000 description 3
• 241000701806 Human papillomavirus Species 0.000 description 3
• 239000004354 Hydroxyethyl cellulose Substances 0.000 description 3
• 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 3
• 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 3
• XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 3
• 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 3
• 206010027209 Meningitis cryptococcal Diseases 0.000 description 3
• 206010062207 Mycobacterial infection Diseases 0.000 description 3
• 208000002193 Pain Diseases 0.000 description 3
• 206010033372 Pain and discomfort Diseases 0.000 description 3
• 206010072353 Painful ejaculation Diseases 0.000 description 3
• 108010071384 Peptide T Proteins 0.000 description 3
• 206010060862 Prostate cancer Diseases 0.000 description 3
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 3
• 208000035415 Reinfection Diseases 0.000 description 3
• NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 description 3
• 108010037442 SPL7013 Proteins 0.000 description 3
• SUJUHGSWHZTSEU-UHFFFAOYSA-N Tipranavir Natural products C1C(O)=C(C(CC)C=2C=C(NS(=O)(=O)C=3N=CC(=CC=3)C(F)(F)F)C=CC=2)C(=O)OC1(CCC)CCC1=CC=CC=C1 SUJUHGSWHZTSEU-UHFFFAOYSA-N 0.000 description 3
• 206010046555 Urinary retention Diseases 0.000 description 3
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 3
• QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 3
• WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 description 3
• UGWQMIXVUBLMAH-IVVFTGHFSA-N [(1s,4r)-4-[2-amino-6-(cyclopropylamino)purin-9-yl]cyclopent-2-en-1-yl]methanol;4-amino-1-[(2r,5s)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1.C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 UGWQMIXVUBLMAH-IVVFTGHFSA-N 0.000 description 3
• 229960004748 abacavir Drugs 0.000 description 3
• MCGSCOLBFJQGHM-SCZZXKLOSA-N abacavir Chemical compound C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 MCGSCOLBFJQGHM-SCZZXKLOSA-N 0.000 description 3
• 229940030360 abacavir / lamivudine Drugs 0.000 description 3
• 229940114030 abacavir / lamivudine / zidovudine Drugs 0.000 description 3
• 210000000683 abdominal cavity Anatomy 0.000 description 3
• 239000002253 acid Substances 0.000 description 3
• 239000012190 activator Substances 0.000 description 3
• 208000009956 adenocarcinoma Diseases 0.000 description 3
• 229960001830 amprenavir Drugs 0.000 description 3
• YMARZQAQMVYCKC-OEMFJLHTSA-N amprenavir Chemical compound C([C@@H]([C@H](O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1COCC1)C1=CC=CC=C1 YMARZQAQMVYCKC-OEMFJLHTSA-N 0.000 description 3
• 208000025009 anogenital human papillomavirus infection Diseases 0.000 description 3
• 201000004201 anogenital venereal wart Diseases 0.000 description 3
• 239000000427 antigen Substances 0.000 description 3
• 102000036639 antigens Human genes 0.000 description 3
• 108091007433 antigens Proteins 0.000 description 3
• RYMCFYKJDVMSIR-RNFRBKRXSA-N apricitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1S[C@H](CO)OC1 RYMCFYKJDVMSIR-RNFRBKRXSA-N 0.000 description 3
• 229960003277 atazanavir Drugs 0.000 description 3
• AXRYRYVKAWYZBR-GASGPIRDSA-N atazanavir Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)[C@@H](O)CN(CC=1C=CC(=CC=1)C=1N=CC=CC=1)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)C1=CC=CC=C1 AXRYRYVKAWYZBR-GASGPIRDSA-N 0.000 description 3
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
• 230000004071 biological effect Effects 0.000 description 3
• 208000034158 bleeding Diseases 0.000 description 3
• NIDRYBLTWYFCFV-UHFFFAOYSA-N calanolide F Natural products C1=CC(C)(C)OC2=C1C(OC(C)C(C)C1O)=C1C1=C2C(CCC)=CC(=O)O1 NIDRYBLTWYFCFV-UHFFFAOYSA-N 0.000 description 3
• 125000004432 carbon atom Chemical group C* 0.000 description 3
• 239000000679 carrageenan Substances 0.000 description 3
• 235000010418 carrageenan Nutrition 0.000 description 3
• 229920001525 carrageenan Polymers 0.000 description 3
• 229940113118 carrageenan Drugs 0.000 description 3
• 239000001913 cellulose Substances 0.000 description 3
• 229920002678 cellulose Polymers 0.000 description 3
• 201000010881 cervical cancer Diseases 0.000 description 3
• JQXXHWHPUNPDRT-BQVAUQFYSA-N chembl1523493 Chemical compound O([C@](C1=O)(C)O\C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)/C=C\C=C(C)/C(=O)NC=2C(O)=C3C(O)=C4C)C)OC)C4=C1C3=C(O)C=2C=NN1CCN(C)CC1 JQXXHWHPUNPDRT-BQVAUQFYSA-N 0.000 description 3
• 229910052801 chlorine Inorganic materials 0.000 description 3
• 230000001684 chronic effect Effects 0.000 description 3
• 238000007796 conventional method Methods 0.000 description 3
• 208000005035 cutaneous candidiasis Diseases 0.000 description 3
• 229960004397 cyclophosphamide Drugs 0.000 description 3
• 229960000684 cytarabine Drugs 0.000 description 3
• 230000003013 cytotoxicity Effects 0.000 description 3
• 231100000135 cytotoxicity Toxicity 0.000 description 3
• 229960005107 darunavir Drugs 0.000 description 3
• CJBJHOAVZSMMDJ-HEXNFIEUSA-N darunavir Chemical compound C([C@@H]([C@H](O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1[C@@H]2CCO[C@@H]2OC1)C1=CC=CC=C1 CJBJHOAVZSMMDJ-HEXNFIEUSA-N 0.000 description 3
• 229960000975 daunorubicin Drugs 0.000 description 3
• STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin 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(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 3
• 229960005319 delavirdine Drugs 0.000 description 3
• 238000001514 detection method Methods 0.000 description 3
• 229960000633 dextran sulfate Drugs 0.000 description 3
• 229960002656 didanosine Drugs 0.000 description 3
• 230000004069 differentiation Effects 0.000 description 3
• 206010013990 dysuria Diseases 0.000 description 3
• 229960003586 elvitegravir Drugs 0.000 description 3
• PEASPLKKXBYDKL-FXEVSJAOSA-N enfuvirtide Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(C)=O)[C@@H](C)O)[C@@H](C)CC)C1=CN=CN1 PEASPLKKXBYDKL-FXEVSJAOSA-N 0.000 description 3
• 229960002062 enfuvirtide Drugs 0.000 description 3
• 229960004884 fluconazole Drugs 0.000 description 3
• RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 description 3
• 229960000390 fludarabine Drugs 0.000 description 3
• 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 3
• 229910052731 fluorine Inorganic materials 0.000 description 3
• 239000011737 fluorine Substances 0.000 description 3
• 229960003142 fosamprenavir Drugs 0.000 description 3
• MLBVMOWEQCZNCC-OEMFJLHTSA-N fosamprenavir Chemical compound C([C@@H]([C@H](OP(O)(O)=O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1COCC1)C1=CC=CC=C1 MLBVMOWEQCZNCC-OEMFJLHTSA-N 0.000 description 3
• 229940050411 fumarate Drugs 0.000 description 3
• 229960003297 gemtuzumab ozogamicin Drugs 0.000 description 3
• 230000035876 healing Effects 0.000 description 3
• 210000002216 heart Anatomy 0.000 description 3
• 238000001794 hormone therapy Methods 0.000 description 3
• 210000005260 human cell Anatomy 0.000 description 3
• 150000002431 hydrogen Chemical class 0.000 description 3
• 230000007062 hydrolysis Effects 0.000 description 3
• 238000006460 hydrolysis reaction Methods 0.000 description 3
• 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 3
• 229950010245 ibalizumab Drugs 0.000 description 3
• 229960000908 idarubicin Drugs 0.000 description 3
• 238000001727 in vivo Methods 0.000 description 3
• 229960001936 indinavir Drugs 0.000 description 3
• CBVCZFGXHXORBI-PXQQMZJSSA-N indinavir Chemical compound C([C@H](N(CC1)C[C@@H](O)C[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H]2C3=CC=CC=C3C[C@H]2O)C(=O)NC(C)(C)C)N1CC1=CC=CN=C1 CBVCZFGXHXORBI-PXQQMZJSSA-N 0.000 description 3
• 239000000411 inducer Substances 0.000 description 3
• 230000002401 inhibitory effect Effects 0.000 description 3
• 230000007794 irritation Effects 0.000 description 3
• 210000003734 kidney Anatomy 0.000 description 3
• 229940033984 lamivudine / zidovudine Drugs 0.000 description 3
• 229940121292 leronlimab Drugs 0.000 description 3
• 210000004185 liver Anatomy 0.000 description 3
• 210000004072 lung Anatomy 0.000 description 3
• GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 3
• 230000002503 metabolic effect Effects 0.000 description 3
• 230000001394 metastastic effect Effects 0.000 description 3
• 206010061289 metastatic neoplasm Diseases 0.000 description 3
• 229960000485 methotrexate Drugs 0.000 description 3
• 208000027531 mycobacterial infectious disease Diseases 0.000 description 3
• 208000025113 myeloid leukemia Diseases 0.000 description 3
• 230000002071 myeloproliferative effect Effects 0.000 description 3
• KMCBHFNNVRCAAH-UHFFFAOYSA-N n,n-dimethyldodecan-1-amine oxide;2-[dodecyl(dimethyl)azaniumyl]acetate Chemical compound CCCCCCCCCCCC[N+](C)(C)[O-].CCCCCCCCCCCC[N+](C)(C)CC([O-])=O KMCBHFNNVRCAAH-UHFFFAOYSA-N 0.000 description 3
• 229960000884 nelfinavir Drugs 0.000 description 3
• QAGYKUNXZHXKMR-HKWSIXNMSA-N nelfinavir Chemical compound CC1=C(O)C=CC=C1C(=O)N[C@H]([C@H](O)CN1[C@@H](C[C@@H]2CCCC[C@@H]2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-HKWSIXNMSA-N 0.000 description 3
• 210000005170 neoplastic cell Anatomy 0.000 description 3
• 230000036565 night sweats Effects 0.000 description 3
• 206010029410 night sweats Diseases 0.000 description 3
• 229940127073 nucleoside analogue Drugs 0.000 description 3
• 230000002611 ovarian Effects 0.000 description 3
• 239000008194 pharmaceutical composition Substances 0.000 description 3
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
• QGVLYPPODPLXMB-QXYKVGAMSA-N phorbol Natural products C[C@@H]1[C@@H](O)[C@]2(O)[C@H]([C@H]3C=C(CO)C[C@@]4(O)[C@H](C=C(C)C4=O)[C@@]13O)C2(C)C QGVLYPPODPLXMB-QXYKVGAMSA-N 0.000 description 3
• 229920000642 polymer Polymers 0.000 description 3
• 238000010837 poor prognosis Methods 0.000 description 3
• IFUKBHBISRAZTF-UHFFFAOYSA-M potassium;4-[(4-fluorophenyl)methylcarbamoyl]-1-methyl-2-[2-[(5-methyl-1,3,4-oxadiazole-2-carbonyl)amino]propan-2-yl]-6-oxopyrimidin-5-olate Chemical compound [K+].O1C(C)=NN=C1C(=O)NC(C)(C)C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C([O-])C(=O)N1C IFUKBHBISRAZTF-UHFFFAOYSA-M 0.000 description 3
• 238000002360 preparation method Methods 0.000 description 3
• 239000003755 preservative agent Substances 0.000 description 3
• 150000003254 radicals Chemical class 0.000 description 3
• 229960004742 raltegravir Drugs 0.000 description 3
• 102000016914 ras Proteins Human genes 0.000 description 3
• 108010014186 ras Proteins Proteins 0.000 description 3
• 208000007865 relapsing fever Diseases 0.000 description 3
• 238000011160 research Methods 0.000 description 3
• 229960000311 ritonavir Drugs 0.000 description 3
• NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 3
• 102200046712 rs752492870 Human genes 0.000 description 3
• 229960001852 saquinavir Drugs 0.000 description 3
• QWAXKHKRTORLEM-UGJKXSETSA-N saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 description 3
• JJICLMJFIKGAAU-UHFFFAOYSA-M sodium;2-amino-9-(1,3-dihydroxypropan-2-yloxymethyl)purin-6-olate Chemical compound [Na+].NC1=NC([O-])=C2N=CN(COC(CO)CO)C2=N1 JJICLMJFIKGAAU-UHFFFAOYSA-M 0.000 description 3
• RMLUKZWYIKEASN-UHFFFAOYSA-M sodium;2-amino-9-(2-hydroxyethoxymethyl)purin-6-olate Chemical compound [Na+].O=C1[N-]C(N)=NC2=C1N=CN2COCCO RMLUKZWYIKEASN-UHFFFAOYSA-M 0.000 description 3
• 229960001203 stavudine Drugs 0.000 description 3
• 210000000130 stem cell Anatomy 0.000 description 3
• 230000001629 suppression Effects 0.000 description 3
• 239000000725 suspension Substances 0.000 description 3
• 230000009747 swallowing Effects 0.000 description 3
• 208000001608 teratocarcinoma Diseases 0.000 description 3
• 229960000838 tipranavir Drugs 0.000 description 3
• SUJUHGSWHZTSEU-FYBSXPHGSA-N tipranavir Chemical compound C([C@@]1(CCC)OC(=O)C([C@H](CC)C=2C=C(NS(=O)(=O)C=3N=CC(=CC=3)C(F)(F)F)C=CC=2)=C(O)C1)CC1=CC=CC=C1 SUJUHGSWHZTSEU-FYBSXPHGSA-N 0.000 description 3
• 210000001364 upper extremity Anatomy 0.000 description 3
• QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 3
• 235000005282 vitamin D3 Nutrition 0.000 description 3
• 239000011647 vitamin D3 Substances 0.000 description 3
• 229940021056 vitamin d3 Drugs 0.000 description 3
• 229960000523 zalcitabine Drugs 0.000 description 3
• UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 3
• VCQRVYCLJARKLE-XQOWHXTBSA-N (1ar,1bs,4ar,7as,7bs,8r,9r,9as)-3-[(acetyloxy)methyl]-4a,7b,9-trihydroxy-1,1,6,8-tetramethyl-5-oxo-1,1a,1b,4,4a,5,7a,7b,8,9-decahydro-9ah-cyclopropa[3,4]benzo[1,2-e]azulen-9a-yl acetate Chemical compound C1=C(COC(C)=O)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](O)[C@@]3(OC(C)=O)C(C)(C)[C@H]3[C@@H]21 VCQRVYCLJARKLE-XQOWHXTBSA-N 0.000 description 2
• GZNWHPFWQMQXII-UHFFFAOYSA-N 1-(2-ethylphenyl)pyrrole-2,5-dione Chemical compound CCC1=CC=CC=C1N1C(=O)C=CC1=O GZNWHPFWQMQXII-UHFFFAOYSA-N 0.000 description 2
• HJEHMBCPVHLCOG-UHFFFAOYSA-N 1-ethynyl-4-propan-2-yloxybenzene Chemical compound CC(C)OC1=CC=C(C#C)C=C1 HJEHMBCPVHLCOG-UHFFFAOYSA-N 0.000 description 2
• GFAGCYRBGVCTPP-UHFFFAOYSA-N 12-deoxyphorbol 13-angelate Natural products C1C(C)C2(O)C3C=C(C)C(=O)C3(O)CC(CO)=CC2C2C1(OC(=O)C(C)=CC)C2(C)C GFAGCYRBGVCTPP-UHFFFAOYSA-N 0.000 description 2
• GFAGCYRBGVCTPP-APZZYBINSA-N 12-deoxyphorbol-13-angelate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)C2)C(CO)=C[C@H]1[C@H]1[C@]2(OC(=O)C(\C)=C/C)C1(C)C GFAGCYRBGVCTPP-APZZYBINSA-N 0.000 description 2
• QSTFRCUXCBXJAW-UHFFFAOYSA-N 12-deoxyphorbol-13-isobutyrate Natural products C1C(C)C2(O)C3C=C(C)C(=O)C3(O)CC(CO)=CC2C2C1(OC(=O)C(C)C)C2(C)C QSTFRCUXCBXJAW-UHFFFAOYSA-N 0.000 description 2
• MTXOHECJOIIIJM-PHFLZNSYSA-N 12-deoxyphorbol-13-isobutyrate-20-acetate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)C2)C(COC(C)=O)=C[C@H]1[C@H]1[C@]2(OC(=O)C(C)C)C1(C)C MTXOHECJOIIIJM-PHFLZNSYSA-N 0.000 description 2
• MTXOHECJOIIIJM-UHFFFAOYSA-N 12-deoxyphorbol-13-isobutyrate-20-acetate Natural products C1C(C)C2(O)C3C=C(C)C(=O)C3(O)CC(COC(C)=O)=CC2C2C1(OC(=O)C(C)C)C2(C)C MTXOHECJOIIIJM-UHFFFAOYSA-N 0.000 description 2
• ZZTJICHINNSOQL-LWYYLCCUSA-N 12-deoxyphorbol-13-tiglate-20-acetate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)C2)C(COC(C)=O)=C[C@H]1[C@H]1[C@]2(OC(=O)C(/C)=C/C)C1(C)C ZZTJICHINNSOQL-LWYYLCCUSA-N 0.000 description 2
• MEDVHSNRBPAIPU-XMOZQXTISA-N 12-deoxyphorbolphenylacetate-20-acetate Chemical compound O([C@]12C[C@H]([C@@]3([C@H]4[C@](C(C(C)=C4)=O)(O)CC(COC(C)=O)=C[C@H]3[C@@H]2C1(C)C)O)C)C(=O)CC1=CC=CC=C1 MEDVHSNRBPAIPU-XMOZQXTISA-N 0.000 description 2
• SDSVJYOOAPRSDA-RPCQODIISA-N 13-Acetylphorbol Chemical compound C1=C(CO)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](O)[C@@]3(OC(C)=O)C(C)(C)[C@H]3[C@@H]21 SDSVJYOOAPRSDA-RPCQODIISA-N 0.000 description 2
• NQSPTMFCJGKOQJ-UHFFFAOYSA-N 2,2,2-trifluoro-1-(3-fluorophenyl)ethanone Chemical compound FC1=CC=CC(C(=O)C(F)(F)F)=C1 NQSPTMFCJGKOQJ-UHFFFAOYSA-N 0.000 description 2
• MGWGTDCOSWKYIL-UHFFFAOYSA-N 2-amino-4-(diaminomethylideneamino)butanoic acid;hydrochloride Chemical compound Cl.OC(=O)C(N)CCN=C(N)N MGWGTDCOSWKYIL-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
• 206010000830 Acute leukaemia Diseases 0.000 description 2
• 206010067484 Adverse reaction Diseases 0.000 description 2
• 102000015790 Asparaginase Human genes 0.000 description 2
• 108010024976 Asparaginase Proteins 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• 102100037904 CD9 antigen Human genes 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• 102100034428 Dual specificity protein phosphatase 1 Human genes 0.000 description 2
• 101710132784 Dual specificity protein phosphatase 1 Proteins 0.000 description 2
• 208000022361 Human papillomavirus infectious disease Diseases 0.000 description 2
• 108010074328 Interferon-gamma Proteins 0.000 description 2
• 108090000174 Interleukin-10 Proteins 0.000 description 2
• 108090000978 Interleukin-4 Proteins 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• 208000007027 Oral Candidiasis Diseases 0.000 description 2
• 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 2
• 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 2
• 108091000080 Phosphotransferase Proteins 0.000 description 2
• 238000010240 RT-PCR analysis Methods 0.000 description 2
• 206010040880 Skin irritation Diseases 0.000 description 2
• YJFFPVQHOKPCRV-LKSXOGJWSA-N [(1S,2S,6R,10S,11R,13S,14R,15R)-1,6,14-trihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-13-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] decanoate Chemical compound C1=C(CO)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](O)[C@@]3(OC(=O)CCCCCCCCC)C(C)(C)[C@H]3[C@@H]21 YJFFPVQHOKPCRV-LKSXOGJWSA-N 0.000 description 2
• CESGKXMBHGUQTB-VONOSFMSSA-N [(1S,2S,6R,10S,11R,13S,14R,15R)-1,6,14-trihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-13-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] tetradecanoate Chemical compound C1=C(CO)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](O)[C@@]3(OC(=O)CCCCCCCCCCCCC)C(C)(C)[C@H]3[C@@H]21 CESGKXMBHGUQTB-VONOSFMSSA-N 0.000 description 2
• 230000002159 abnormal effect Effects 0.000 description 2
• LMLOFRDITXUVHZ-BPNNYVJBSA-N ac1l3xbq Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(=O)CC)C1(C)C LMLOFRDITXUVHZ-BPNNYVJBSA-N 0.000 description 2
• FDFRQMKAXPLXFL-UZAJRZOCSA-N ac1l576h Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)C2)C(CO)=C[C@H]1[C@H]1[C@]2(OC(=O)CCCCCCCCCCCCC)C1(C)C FDFRQMKAXPLXFL-UZAJRZOCSA-N 0.000 description 2
• 150000001242 acetic acid derivatives Chemical class 0.000 description 2
• 239000000654 additive Substances 0.000 description 2
• 239000002671 adjuvant Substances 0.000 description 2
• 230000006838 adverse reaction Effects 0.000 description 2
• 230000036436 anti-hiv Effects 0.000 description 2
• 230000003110 anti-inflammatory effect Effects 0.000 description 2
• 230000000719 anti-leukaemic effect Effects 0.000 description 2
• 230000002365 anti-tubercular Effects 0.000 description 2
• 238000013459 approach Methods 0.000 description 2
• 229960003272 asparaginase Drugs 0.000 description 2
• DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical compound [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 0.000 description 2
• 125000004429 atom Chemical group 0.000 description 2
• 239000012752 auxiliary agent Substances 0.000 description 2
• VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 2
• 238000001574 biopsy Methods 0.000 description 2
• 210000000601 blood cell Anatomy 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 229960004562 carboplatin Drugs 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
• 238000013270 controlled release Methods 0.000 description 2
• 229940117173 croton oil Drugs 0.000 description 2
• 108060002021 cyanovirin N Proteins 0.000 description 2
• 230000002559 cytogenic effect Effects 0.000 description 2
• 230000000994 depressogenic effect Effects 0.000 description 2
• 229930004069 diterpene Natural products 0.000 description 2
• 125000000567 diterpene group Chemical group 0.000 description 2
• 239000003937 drug carrier Substances 0.000 description 2
• 238000012377 drug delivery Methods 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 238000005516 engineering process Methods 0.000 description 2
• 239000000284 extract Substances 0.000 description 2
• 230000004438 eyesight Effects 0.000 description 2
• 230000002349 favourable effect Effects 0.000 description 2
• 239000000945 filler Substances 0.000 description 2
• 229910052736 halogen Inorganic materials 0.000 description 2
• 150000002367 halogens Chemical group 0.000 description 2
• 238000005534 hematocrit Methods 0.000 description 2
• 230000006882 induction of apoptosis Effects 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• 238000007918 intramuscular administration Methods 0.000 description 2
• 238000007912 intraperitoneal administration Methods 0.000 description 2
• 230000002045 lasting effect Effects 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• 230000007774 longterm Effects 0.000 description 2
• 230000036210 malignancy Effects 0.000 description 2
• 238000007726 management method Methods 0.000 description 2
• 238000004519 manufacturing process Methods 0.000 description 2
• 230000003340 mental effect Effects 0.000 description 2
• 229960001428 mercaptopurine Drugs 0.000 description 2
• 239000003094 microcapsule Substances 0.000 description 2
• 239000004005 microsphere Substances 0.000 description 2
• KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 2
• 229960001156 mitoxantrone Drugs 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 239000002773 nucleotide Substances 0.000 description 2
• 125000003729 nucleotide group Chemical group 0.000 description 2
• 206010030979 oral hairy leukoplakia Diseases 0.000 description 2
• 150000002894 organic compounds Chemical class 0.000 description 2
• 230000036961 partial effect Effects 0.000 description 2
• LASMKIAVFGUYEG-SEYWVDNQSA-N phorbol 12,13,20-triacetate Chemical compound C1=C(COC(C)=O)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](OC(C)=O)[C@@]3(OC(C)=O)C(C)(C)[C@H]3[C@@H]21 LASMKIAVFGUYEG-SEYWVDNQSA-N 0.000 description 2
• BQJRUJTZSGYBEZ-YVQNUNKESA-N phorbol 12,13-dibutanoate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(=O)CCC)C1(C)C BQJRUJTZSGYBEZ-YVQNUNKESA-N 0.000 description 2
• NVKVYBPQQUTLSY-RPCQODIISA-N phorbol 12-acetate Chemical compound C1=C(CO)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](OC(C)=O)[C@@]3(O)C(C)(C)[C@H]3[C@@H]21 NVKVYBPQQUTLSY-RPCQODIISA-N 0.000 description 2
• LXYSVTVLQYLWKR-LKSXOGJWSA-N phorbol 12-decanoate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(O)C1(C)C LXYSVTVLQYLWKR-LKSXOGJWSA-N 0.000 description 2
• FZXHDWWEDNRATG-JUDMOCROSA-N phorbol 13-butanoate Chemical compound C1=C(CO)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](O)[C@@]3(OC(=O)CCC)C(C)(C)[C@H]3[C@@H]21 FZXHDWWEDNRATG-JUDMOCROSA-N 0.000 description 2
• QWYNFKKVBDGBLL-KFWZAFQTSA-N phorbol 13-decanoate 12-tiglate Chemical compound C1=C(CO)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](OC(=O)C(\C)=C\C)[C@@]3(OC(=O)CCCCCCCCC)C(C)(C)[C@H]3[C@@H]21 QWYNFKKVBDGBLL-KFWZAFQTSA-N 0.000 description 2
• DGOSGFYDFDYMCW-MWRBZVGOSA-N phorbol dicaprate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(=O)CCCCCCCCC)C1(C)C DGOSGFYDFDYMCW-MWRBZVGOSA-N 0.000 description 2
• XGPRSRGBAHBMAF-NQWCLMGHSA-N phorbol-12,13-dihexanoate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(=O)CCCCC)C1(C)C XGPRSRGBAHBMAF-NQWCLMGHSA-N 0.000 description 2
• XLCISDOVNFLSGO-VONOSFMSSA-N phorbol-12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(O)C1(C)C XLCISDOVNFLSGO-VONOSFMSSA-N 0.000 description 2
• 102000020233 phosphotransferase Human genes 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• 102000005962 receptors Human genes 0.000 description 2
• 108020003175 receptors Proteins 0.000 description 2
• 238000011084 recovery Methods 0.000 description 2
• 230000002829 reductive effect Effects 0.000 description 2
• 230000001105 regulatory effect Effects 0.000 description 2
• 230000029058 respiratory gaseous exchange Effects 0.000 description 2
• 230000001177 retroviral effect Effects 0.000 description 2
• 239000000523 sample Substances 0.000 description 2
• 201000000306 sarcoidosis Diseases 0.000 description 2
• 230000011664 signaling Effects 0.000 description 2
• 231100000475 skin irritation Toxicity 0.000 description 2
• 230000036556 skin irritation Effects 0.000 description 2
• 239000000375 suspending agent Substances 0.000 description 2
• 150000003892 tartrate salts Chemical class 0.000 description 2
• CGVXVPQJMYMMIH-HKDZDBKOSA-N tigliane Chemical compound C1[C@H](C)C[C@H]2[C@@H]3C(C)(C)[C@@H]3C[C@@H](C)[C@@H]2[C@@H]2C[C@H](C)C[C@H]21 CGVXVPQJMYMMIH-HKDZDBKOSA-N 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
• 210000001519 tissue Anatomy 0.000 description 2
• 231100000331 toxic Toxicity 0.000 description 2
• 230000002588 toxic effect Effects 0.000 description 2
• KYLIMUJRJDIPPF-UHFFFAOYSA-N trisalicylate Chemical compound O=C1OC2=CC=CC=C2C(=O)OC2=CC=CC=C2C(=O)OC2=CC=CC=C12 KYLIMUJRJDIPPF-UHFFFAOYSA-N 0.000 description 2
• 239000000717 tumor promoter Substances 0.000 description 2
• 230000009385 viral infection Effects 0.000 description 2
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
• 230000003442 weekly effect Effects 0.000 description 2
• 238000001262 western blot Methods 0.000 description 2
• BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical class CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
• RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
• 102100027211 Albumin Human genes 0.000 description 1
• 108010088751 Albumins Proteins 0.000 description 1
• 201000004384 Alopecia Diseases 0.000 description 1
• 208000032800 BCR-ABL1 positive blast phase chronic myelogenous leukemia Diseases 0.000 description 1
• 241000193830 Bacillus <bacterium> Species 0.000 description 1
• 208000004860 Blast Crisis Diseases 0.000 description 1
• 201000004569 Blindness Diseases 0.000 description 1
• 102000004506 Blood Proteins Human genes 0.000 description 1
• 108010017384 Blood Proteins Proteins 0.000 description 1
• 208000018084 Bone neoplasm Diseases 0.000 description 1
• 206010006784 Burning sensation Diseases 0.000 description 1
• 210000001666 CD4-positive, alpha-beta memory T lymphocyte Anatomy 0.000 description 1
• 101100510326 Caenorhabditis elegans tpa-1 gene Proteins 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 208000005623 Carcinogenesis Diseases 0.000 description 1
• 241000700199 Cavia porcellus Species 0.000 description 1
• 206010007953 Central nervous system lymphoma Diseases 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• 102000003712 Complement factor B Human genes 0.000 description 1
• 108090000056 Complement factor B Proteins 0.000 description 1
• OCUCCJIRFHNWBP-IYEMJOQQSA-L Copper gluconate Chemical class [Cu+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O OCUCCJIRFHNWBP-IYEMJOQQSA-L 0.000 description 1
• 238000000018 DNA microarray Methods 0.000 description 1
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
• 241000221017 Euphorbiaceae Species 0.000 description 1
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
• 206010017533 Fungal infection Diseases 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 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 1
• 108090000288 Glycoproteins Proteins 0.000 description 1
• 102000003886 Glycoproteins Human genes 0.000 description 1
• 102000006481 HIV Receptors Human genes 0.000 description 1
• 108010083930 HIV Receptors Proteins 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• 102100034343 Integrase Human genes 0.000 description 1
• 238000012695 Interfacial polymerization Methods 0.000 description 1
• 108010078049 Interferon alpha-2 Proteins 0.000 description 1
• 102100039350 Interferon alpha-7 Human genes 0.000 description 1
• 102100037850 Interferon gamma Human genes 0.000 description 1
• 102000008070 Interferon-gamma Human genes 0.000 description 1
• 108010002616 Interleukin-5 Proteins 0.000 description 1
• 102000015696 Interleukins Human genes 0.000 description 1
• 108010063738 Interleukins Proteins 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 102000001291 MAP Kinase Kinase Kinase Human genes 0.000 description 1
• 108060006687 MAP kinase kinase kinase Proteins 0.000 description 1
• 239000004907 Macro-emulsion Substances 0.000 description 1
• 206010025476 Malabsorption Diseases 0.000 description 1
• 208000004155 Malabsorption Syndromes Diseases 0.000 description 1
• 241000699666 Mus <mouse, genus> Species 0.000 description 1
• 208000031888 Mycoses Diseases 0.000 description 1
• HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• 206010028813 Nausea Diseases 0.000 description 1
• 206010061309 Neoplasm progression Diseases 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• 206010067482 No adverse event Diseases 0.000 description 1
• 108091034117 Oligonucleotide Proteins 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 241001631646 Papillomaviridae Species 0.000 description 1
• 108091005804 Peptidases Proteins 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
• 208000005384 Pneumocystis Pneumonia Diseases 0.000 description 1
• 206010073755 Pneumocystis jirovecii pneumonia Diseases 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 239000004365 Protease Substances 0.000 description 1
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
• 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
• 241000700159 Rattus Species 0.000 description 1
• 206010062237 Renal impairment Diseases 0.000 description 1
• 206010057190 Respiratory tract infections Diseases 0.000 description 1
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
• 208000006268 Sarcoma 180 Diseases 0.000 description 1
• 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 1
• 206010066901 Treatment failure Diseases 0.000 description 1
• GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical class OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 1
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
• 206010046306 Upper respiratory tract infection Diseases 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• 208000000260 Warts Diseases 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 208000036676 acute undifferentiated leukemia Diseases 0.000 description 1
• 150000001447 alkali salts Chemical class 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 230000009435 amidation Effects 0.000 description 1
• 238000007112 amidation reaction Methods 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 125000004103 aminoalkyl group Chemical group 0.000 description 1
• 150000008064 anhydrides Chemical class 0.000 description 1
• 230000002424 anti-apoptotic effect Effects 0.000 description 1
• 229940121363 anti-inflammatory agent Drugs 0.000 description 1
• 239000002260 anti-inflammatory agent Substances 0.000 description 1
• 230000000118 anti-neoplastic effect Effects 0.000 description 1
• 239000003793 antidiarrheal agent Substances 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 230000003385 bacteriostatic effect Effects 0.000 description 1
• 239000003855 balanced salt solution Substances 0.000 description 1
• 230000004888 barrier function Effects 0.000 description 1
• 229940088007 benadryl Drugs 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 238000004166 bioassay Methods 0.000 description 1
• 239000012472 biological sample Substances 0.000 description 1
• 210000003969 blast cell Anatomy 0.000 description 1
• 230000017531 blood circulation Effects 0.000 description 1
• 230000036765 blood level Effects 0.000 description 1
• 208000027503 bloody stool Diseases 0.000 description 1
• 238000007470 bone biopsy Methods 0.000 description 1
• 238000009583 bone marrow aspiration Methods 0.000 description 1
• 210000002798 bone marrow cell Anatomy 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 230000036952 cancer formation Effects 0.000 description 1
• 229910052799 carbon Inorganic materials 0.000 description 1
• 231100000504 carcinogenesis Toxicity 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 230000030833 cell death Effects 0.000 description 1
• 230000032823 cell division Effects 0.000 description 1
• 230000007969 cellular immunity Effects 0.000 description 1
• 159000000006 cesium salts Chemical class 0.000 description 1
• 229940044683 chemotherapy drug Drugs 0.000 description 1
• 235000012000 cholesterol Nutrition 0.000 description 1
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
• 229960001231 choline Drugs 0.000 description 1
• 150000001860 citric acid derivatives Chemical class 0.000 description 1
• 238000005354 coacervation Methods 0.000 description 1
• 238000012733 comparative method Methods 0.000 description 1
• 239000012084 conversion product Substances 0.000 description 1
• 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
• GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 1
• 210000004443 dendritic cell Anatomy 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 150000001982 diacylglycerols Chemical class 0.000 description 1
• JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical class OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 description 1
• 239000006185 dispersion Substances 0.000 description 1
• 231100000371 dose-limiting toxicity Toxicity 0.000 description 1
• 230000007783 downstream signaling Effects 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 230000008482 dysregulation Effects 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 230000008029 eradication Effects 0.000 description 1
• 230000032050 esterification Effects 0.000 description 1
• 238000005886 esterification reaction Methods 0.000 description 1
• 150000002169 ethanolamines Chemical class 0.000 description 1
• 229960000752 etoposide phosphate 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
• 230000029142 excretion Effects 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 210000003608 fece Anatomy 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 229960004279 formaldehyde Drugs 0.000 description 1
• 235000019256 formaldehyde Nutrition 0.000 description 1
• 150000004675 formic acid derivatives Chemical class 0.000 description 1
• 230000006870 function Effects 0.000 description 1
• 230000005714 functional activity Effects 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 210000004602 germ cell Anatomy 0.000 description 1
• 150000002306 glutamic acid derivatives Chemical class 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 230000003676 hair loss Effects 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 230000003862 health status Effects 0.000 description 1
• 208000035861 hematochezia Diseases 0.000 description 1
• 230000002489 hematologic effect Effects 0.000 description 1
• 230000028996 humoral immune response Effects 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
• 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
• 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• 230000036737 immune function Effects 0.000 description 1
• 230000008629 immune suppression Effects 0.000 description 1
• 229960001438 immunostimulant agent Drugs 0.000 description 1
• 239000003022 immunostimulating agent Substances 0.000 description 1
• 230000003308 immunostimulating effect Effects 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 230000002458 infectious effect Effects 0.000 description 1
• 230000002757 inflammatory effect Effects 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 229960003130 interferon gamma Drugs 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 238000000185 intracerebroventricular administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 230000001788 irregular Effects 0.000 description 1
• 230000002147 killing effect Effects 0.000 description 1
• 229940043355 kinase inhibitor Drugs 0.000 description 1
• 238000002372 labelling Methods 0.000 description 1
• 150000003893 lactate salts Chemical class 0.000 description 1
• 230000000292 leukogenic effect Effects 0.000 description 1
• 208000002741 leukoplakia Diseases 0.000 description 1
• 239000002502 liposome Substances 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 230000004807 localization Effects 0.000 description 1
• 208000018769 loss of vision Diseases 0.000 description 1
• 231100000864 loss of vision Toxicity 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 210000004324 lymphatic system Anatomy 0.000 description 1
• 210000004698 lymphocyte Anatomy 0.000 description 1
• 210000002540 macrophage Anatomy 0.000 description 1
• GVALZJMUIHGIMD-UHFFFAOYSA-H magnesium phosphate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GVALZJMUIHGIMD-UHFFFAOYSA-H 0.000 description 1
• 239000004137 magnesium phosphate Substances 0.000 description 1
• 229960002261 magnesium phosphate Drugs 0.000 description 1
• 229910000157 magnesium phosphate Inorganic materials 0.000 description 1
• 235000010994 magnesium phosphates Nutrition 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 150000002688 maleic acid derivatives Chemical class 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
• 239000004530 micro-emulsion Substances 0.000 description 1
• 239000011859 microparticle Substances 0.000 description 1
• 238000007431 microscopic evaluation Methods 0.000 description 1
• 230000003278 mimic effect Effects 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 230000000116 mitigating effect Effects 0.000 description 1
• 201000000050 myeloid neoplasm Diseases 0.000 description 1
• 229940105132 myristate Drugs 0.000 description 1
• ACTNHJDHMQSOGL-UHFFFAOYSA-N n',n'-dibenzylethane-1,2-diamine Chemical class C=1C=CC=CC=1CN(CCN)CC1=CC=CC=C1 ACTNHJDHMQSOGL-UHFFFAOYSA-N 0.000 description 1
• 239000002088 nanocapsule Substances 0.000 description 1
• 239000002105 nanoparticle Substances 0.000 description 1
• 201000009240 nasopharyngitis Diseases 0.000 description 1
• 230000008693 nausea Effects 0.000 description 1
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
• 229910052757 nitrogen Inorganic materials 0.000 description 1
• 231100001223 noncarcinogenic Toxicity 0.000 description 1
• 239000002777 nucleoside Substances 0.000 description 1
• 150000003833 nucleoside derivatives Chemical class 0.000 description 1
• 230000000771 oncological effect Effects 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 230000001151 other effect Effects 0.000 description 1
• 150000003891 oxalate salts Chemical class 0.000 description 1
• 230000003647 oxidation Effects 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 229910052760 oxygen Inorganic materials 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 210000004976 peripheral blood cell Anatomy 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• 230000002085 persistent effect Effects 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• 230000003285 pharmacodynamic effect Effects 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 239000011574 phosphorus Substances 0.000 description 1
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
• 230000001766 physiological effect Effects 0.000 description 1
• 230000035479 physiological effects, processes and functions Effects 0.000 description 1
• 239000000902 placebo Substances 0.000 description 1
• 229940068196 placebo Drugs 0.000 description 1
• 201000000317 pneumocystosis Diseases 0.000 description 1
• 239000002798 polar solvent Substances 0.000 description 1
• 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
• 239000004926 polymethyl methacrylate Substances 0.000 description 1
• 231100000857 poor renal function Toxicity 0.000 description 1
• 231100000683 possible toxicity Toxicity 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
• 208000016800 primary central nervous system lymphoma Diseases 0.000 description 1
• 230000035755 proliferation Effects 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 238000002106 pulse oximetry Methods 0.000 description 1
• 150000003222 pyridines Chemical class 0.000 description 1
• 230000005855 radiation Effects 0.000 description 1
• 101150087683 rasgrp1 gene Proteins 0.000 description 1
• 238000006722 reduction reaction Methods 0.000 description 1
• 210000002345 respiratory system Anatomy 0.000 description 1
• 208000020029 respiratory tract infectious disease Diseases 0.000 description 1
• 230000000284 resting effect Effects 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 208000037921 secondary disease Diseases 0.000 description 1
• 231100000847 severe hepatotoxicity Toxicity 0.000 description 1
• 231100001068 severe skin irritation Toxicity 0.000 description 1
• 201000010153 skin papilloma Diseases 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• 210000000278 spinal cord Anatomy 0.000 description 1
• 230000006641 stabilisation Effects 0.000 description 1
• 238000011105 stabilization Methods 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 238000011255 standard chemotherapy Methods 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 238000011272 standard treatment Methods 0.000 description 1
• 238000005728 strengthening Methods 0.000 description 1
• 125000001424 substituent group Chemical group 0.000 description 1
• 150000003890 succinate salts Chemical class 0.000 description 1
• RINCXYDBBGOEEQ-UHFFFAOYSA-N succinic anhydride Chemical compound O=C1CCC(=O)O1 RINCXYDBBGOEEQ-UHFFFAOYSA-N 0.000 description 1
• 125000001273 sulfonato group Chemical class [O-]S(*)(=O)=O 0.000 description 1
• 239000013589 supplement Substances 0.000 description 1
• 230000007755 survival signaling Effects 0.000 description 1
• 208000010648 susceptibility to HIV infection Diseases 0.000 description 1
• 230000035900 sweating Effects 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 238000002636 symptomatic treatment Methods 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 210000000779 thoracic wall Anatomy 0.000 description 1
• 208000014754 thrombocytosis disease Diseases 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• 210000004881 tumor cell Anatomy 0.000 description 1
• 230000005748 tumor development Effects 0.000 description 1
• 230000004614 tumor growth Effects 0.000 description 1
• 230000005751 tumor progression Effects 0.000 description 1
• 229940072651 tylenol Drugs 0.000 description 1
• 241001529453 unidentified herpesvirus Species 0.000 description 1
• 241001430294 unidentified retrovirus Species 0.000 description 1
• 230000029812 viral genome replication Effects 0.000 description 1
• 230000000007 visual effect Effects 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1