CA2868024A1 - Methods of treating cancer using aurora kinase inhibitors - Google Patents

Info

Publication number

CA2868024A1

CA2868024A1 CA2868024A CA2868024A CA2868024A1 CA 2868024 A1 CA2868024 A1 CA 2868024A1 CA 2868024 A CA2868024 A CA 2868024A CA 2868024 A CA2868024 A CA 2868024A CA 2868024 A1 CA2868024 A1 CA 2868024A1

Authority

CA

Canada

Prior art keywords

cancer

alisertib

aurora

paclitaxel

dose

Prior art date

2012-03-20

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 206010028980 Neoplasm Diseases 0.000 title claims description 128
• 201000011510 cancer Diseases 0.000 title claims description 74
• 238000000034 method Methods 0.000 title abstract description 34
• 239000003719 aurora kinase inhibitor Substances 0.000 title description 2
• 229930012538 Paclitaxel Natural products 0.000 claims abstract description 86
• 229960001592 paclitaxel Drugs 0.000 claims abstract description 86
• 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 abstract description 86
• 230000002062 proliferating effect Effects 0.000 claims abstract description 26
• ZLHFILGSQDJULK-UHFFFAOYSA-N 4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxybenzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC(NC=2N=C3C4=CC=C(Cl)C=C4C(=NCC3=CN=2)C=2C(=CC=CC=2F)OC)=C1 ZLHFILGSQDJULK-UHFFFAOYSA-N 0.000 claims description 72
• 229950009447 alisertib Drugs 0.000 claims description 69
• 239000003814 drug Substances 0.000 claims description 52
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 45
• 150000003839 salts Chemical class 0.000 claims description 25
• 206010041067 Small cell lung cancer Diseases 0.000 claims description 20
• 208000000587 small cell lung carcinoma Diseases 0.000 claims description 20
• 208000026310 Breast neoplasm Diseases 0.000 claims description 16
• 206010006187 Breast cancer Diseases 0.000 claims description 15
• 206010033128 Ovarian cancer Diseases 0.000 claims description 13
• 206010061535 Ovarian neoplasm Diseases 0.000 claims description 12
• 208000020816 lung neoplasm Diseases 0.000 claims description 9
• 208000007766 Kaposi sarcoma Diseases 0.000 claims description 8
• 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 8
• 201000005202 lung cancer Diseases 0.000 claims description 8
• 208000030507 AIDS Diseases 0.000 claims description 6
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 5
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 5
• 238000004519 manufacturing process Methods 0.000 claims description 5
• 206010005003 Bladder cancer Diseases 0.000 claims description 4
• 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 4
• 206010060862 Prostate cancer Diseases 0.000 claims description 4
• 208000005718 Stomach Neoplasms Diseases 0.000 claims description 4
• 206010017758 gastric cancer Diseases 0.000 claims description 4
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 4
• 208000008443 pancreatic carcinoma Diseases 0.000 claims description 4
• 201000011549 stomach cancer Diseases 0.000 claims description 4
• 201000005112 urinary bladder cancer Diseases 0.000 claims description 4
• 201000010536 head and neck cancer Diseases 0.000 claims description 3
• 208000014829 head and neck neoplasm Diseases 0.000 claims description 3
• 201000002528 pancreatic cancer Diseases 0.000 claims description 3
• 102000004000 Aurora Kinase A Human genes 0.000 abstract description 115
• 108090000461 Aurora Kinase A Proteins 0.000 abstract description 115
• 238000011282 treatment Methods 0.000 abstract description 74
• 229940124639 Selective inhibitor Drugs 0.000 abstract description 51
• 229940123237 Taxane Drugs 0.000 abstract description 45
• DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 abstract description 33
• 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 abstract description 11
• 229960003668 docetaxel Drugs 0.000 abstract description 11
• 238000002512 chemotherapy Methods 0.000 abstract description 5
• 210000004027 cell Anatomy 0.000 description 96
• 239000003795 chemical substances by application Substances 0.000 description 50
• 150000001875 compounds Chemical class 0.000 description 49
• -1 MGC34538 Proteins 0.000 description 46
• 125000003118 aryl group Chemical group 0.000 description 41
• 230000003442 weekly effect Effects 0.000 description 39
• 125000001072 heteroaryl group Chemical group 0.000 description 31
• 230000000694 effects Effects 0.000 description 28
• 125000000623 heterocyclic group Chemical group 0.000 description 28
• 229940043355 kinase inhibitor Drugs 0.000 description 28
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 28
• 229940124597 therapeutic agent Drugs 0.000 description 28
• 208000035475 disorder Diseases 0.000 description 27
• 239000003112 inhibitor Substances 0.000 description 27
• 239000000203 mixture Substances 0.000 description 27
• 125000001931 aliphatic group Chemical group 0.000 description 26
• 235000002639 sodium chloride Nutrition 0.000 description 24
• 125000001424 substituent group Chemical group 0.000 description 23
• 229910052757 nitrogen Inorganic materials 0.000 description 20
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 20
• 230000000259 anti-tumor effect Effects 0.000 description 19
• 230000000394 mitotic effect Effects 0.000 description 19
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 15
• 230000002195 synergetic effect Effects 0.000 description 15
• 241001465754 Metazoa Species 0.000 description 14
• 210000000349 chromosome Anatomy 0.000 description 14
• 201000010099 disease Diseases 0.000 description 14
• 229940079593 drug Drugs 0.000 description 14
• 230000005764 inhibitory process Effects 0.000 description 14
• 231100000682 maximum tolerated dose Toxicity 0.000 description 14
• 108090000623 proteins and genes Proteins 0.000 description 14
• 230000001225 therapeutic effect Effects 0.000 description 14
• 125000000217 alkyl group Chemical group 0.000 description 13
• 230000022131 cell cycle Effects 0.000 description 13
• 239000008194 pharmaceutical composition Substances 0.000 description 13
• 239000003981 vehicle Substances 0.000 description 13
• 239000000654 additive Substances 0.000 description 12
• 230000000996 additive effect Effects 0.000 description 12
• 238000002648 combination therapy Methods 0.000 description 12
• 102000004169 proteins and genes Human genes 0.000 description 12
• 241000699670 Mus sp. Species 0.000 description 11
• 239000005441 aurora Substances 0.000 description 11
• 125000005842 heteroatom Chemical group 0.000 description 11
• 238000001727 in vivo Methods 0.000 description 11
• 230000011278 mitosis Effects 0.000 description 11
• 230000004044 response Effects 0.000 description 11
• 125000006413 ring segment Chemical group 0.000 description 11
• 238000002560 therapeutic procedure Methods 0.000 description 11
• 239000002246 antineoplastic agent Substances 0.000 description 10
• 239000002552 dosage form Substances 0.000 description 10
• 230000006870 function Effects 0.000 description 10
• 208000004235 neutropenia Diseases 0.000 description 10
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
• 108010002350 Interleukin-2 Proteins 0.000 description 9
• 102000000588 Interleukin-2 Human genes 0.000 description 9
• 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 9
• 231100000371 dose-limiting toxicity Toxicity 0.000 description 9
• 229910052739 hydrogen Inorganic materials 0.000 description 9
• 239000001257 hydrogen Substances 0.000 description 9
• 102000004127 Cytokines Human genes 0.000 description 8
• 108090000695 Cytokines Proteins 0.000 description 8
• 239000003080 antimitotic agent Substances 0.000 description 8
• 210000000481 breast Anatomy 0.000 description 8
• 230000030833 cell death Effects 0.000 description 8
• 230000004663 cell proliferation Effects 0.000 description 8
• 230000007547 defect Effects 0.000 description 8
• 230000002255 enzymatic effect Effects 0.000 description 8
• 230000012010 growth Effects 0.000 description 8
• 239000003826 tablet Substances 0.000 description 8
• 231100000419 toxicity Toxicity 0.000 description 8
• 230000001988 toxicity Effects 0.000 description 8
• 241000196324 Embryophyta Species 0.000 description 7
• 239000000427 antigen Substances 0.000 description 7
• 108091007433 antigens Proteins 0.000 description 7
• 102000036639 antigens Human genes 0.000 description 7
• 239000002256 antimetabolite Substances 0.000 description 7
• 230000008901 benefit Effects 0.000 description 7
• 229940127089 cytotoxic agent Drugs 0.000 description 7
• 238000000338 in vitro Methods 0.000 description 7
• 230000002401 inhibitory effect Effects 0.000 description 7
• 210000004072 lung Anatomy 0.000 description 7
• 125000004433 nitrogen atom Chemical group N* 0.000 description 7
• 239000000243 solution Substances 0.000 description 7
• 239000002904 solvent Substances 0.000 description 7
• 239000000126 substance Substances 0.000 description 7
• 229910052717 sulfur Inorganic materials 0.000 description 7
• 230000004614 tumor growth Effects 0.000 description 7
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
• 102100032311 Aurora kinase A Human genes 0.000 description 6
• 102000004228 Aurora kinase B Human genes 0.000 description 6
• 108090000749 Aurora kinase B Proteins 0.000 description 6
• 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 6
• 108020004414 DNA Proteins 0.000 description 6
• 101000798300 Homo sapiens Aurora kinase A Proteins 0.000 description 6
• 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 6
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
• 102000029749 Microtubule Human genes 0.000 description 6
• 108091022875 Microtubule Proteins 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• 125000003710 aryl alkyl group Chemical group 0.000 description 6
• 230000015572 biosynthetic process Effects 0.000 description 6
• 239000002775 capsule Substances 0.000 description 6
• 150000001721 carbon Chemical group 0.000 description 6
• 230000010261 cell growth Effects 0.000 description 6
• 230000001413 cellular effect Effects 0.000 description 6
• 239000003937 drug carrier Substances 0.000 description 6
• 125000005843 halogen group Chemical group 0.000 description 6
• 229940125697 hormonal agent Drugs 0.000 description 6
• 238000001990 intravenous administration Methods 0.000 description 6
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
• 239000000463 material Substances 0.000 description 6
• 210000004688 microtubule Anatomy 0.000 description 6
• 230000036456 mitotic arrest Effects 0.000 description 6
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 6
• 239000000546 pharmaceutical excipient Substances 0.000 description 6
• 229920001223 polyethylene glycol Polymers 0.000 description 6
• 239000011734 sodium Substances 0.000 description 6
• 229910052708 sodium Inorganic materials 0.000 description 6
• 239000007787 solid Substances 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• 238000003786 synthesis reaction Methods 0.000 description 6
• 210000004881 tumor cell Anatomy 0.000 description 6
• 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 5
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
• 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 5
• 206010035226 Plasma cell myeloma Diseases 0.000 description 5
• 108700025716 Tumor Suppressor Genes Proteins 0.000 description 5
• 102000044209 Tumor Suppressor Genes Human genes 0.000 description 5
• 239000002168 alkylating agent Substances 0.000 description 5
• 229940100198 alkylating agent Drugs 0.000 description 5
• 125000002947 alkylene group Chemical group 0.000 description 5
• 229910052799 carbon Inorganic materials 0.000 description 5
• 230000032823 cell division Effects 0.000 description 5
• 238000000576 coating method Methods 0.000 description 5
• 210000001072 colon Anatomy 0.000 description 5
• 230000001419 dependent effect Effects 0.000 description 5
• 230000014509 gene expression Effects 0.000 description 5
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
• 239000008101 lactose Substances 0.000 description 5
• 239000008297 liquid dosage form Substances 0.000 description 5
• 239000000314 lubricant Substances 0.000 description 5
• 239000002609 medium Substances 0.000 description 5
• 125000006574 non-aromatic ring group Chemical group 0.000 description 5
• 230000002611 ovarian Effects 0.000 description 5
• 239000006187 pill Substances 0.000 description 5
• 239000000843 powder Substances 0.000 description 5
• 230000002035 prolonged effect Effects 0.000 description 5
• 210000002307 prostate Anatomy 0.000 description 5
• 150000003254 radicals Chemical class 0.000 description 5
• 229920006395 saturated elastomer Polymers 0.000 description 5
• 239000007909 solid dosage form Substances 0.000 description 5
• 230000024355 spindle assembly checkpoint Effects 0.000 description 5
• 239000000758 substrate Substances 0.000 description 5
• 210000001519 tissue Anatomy 0.000 description 5
• 210000003932 urinary bladder Anatomy 0.000 description 5
• 239000001993 wax Substances 0.000 description 5
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 4
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 4
• 206010004446 Benign prostatic hyperplasia 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
• 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 4
• 206010061598 Immunodeficiency Diseases 0.000 description 4
• 208000034578 Multiple myelomas Diseases 0.000 description 4
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 4
• 208000004403 Prostatic Hyperplasia Diseases 0.000 description 4
• 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 4
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
• 229920002472 Starch Polymers 0.000 description 4
• 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 4
• 229930006000 Sucrose Natural products 0.000 description 4
• 230000002159 abnormal effect Effects 0.000 description 4
• 238000010521 absorption reaction Methods 0.000 description 4
• 239000002671 adjuvant Substances 0.000 description 4
• 235000010443 alginic acid Nutrition 0.000 description 4
• 229920000615 alginic acid Polymers 0.000 description 4
• 229940044684 anti-microtubule agent Drugs 0.000 description 4
• 238000003556 assay Methods 0.000 description 4
• 230000003115 biocidal effect Effects 0.000 description 4
• 239000003124 biologic agent Substances 0.000 description 4
• 125000004432 carbon atom Chemical group C* 0.000 description 4
• 230000001351 cycling effect Effects 0.000 description 4
• 230000003247 decreasing effect Effects 0.000 description 4
• 230000003111 delayed effect Effects 0.000 description 4
• 238000011161 development Methods 0.000 description 4
• 230000018109 developmental process Effects 0.000 description 4
• 239000003995 emulsifying agent Substances 0.000 description 4
• 125000001153 fluoro group Chemical group F* 0.000 description 4
• 239000012634 fragment Substances 0.000 description 4
• 125000002541 furyl group Chemical group 0.000 description 4
• 230000002496 gastric effect Effects 0.000 description 4
• 239000008187 granular material Substances 0.000 description 4
• 125000004475 heteroaralkyl group Chemical group 0.000 description 4
• 229930195733 hydrocarbon Natural products 0.000 description 4
• 230000003463 hyperproliferative effect Effects 0.000 description 4
• 230000028993 immune response Effects 0.000 description 4
• 239000003701 inert diluent Substances 0.000 description 4
• 238000002347 injection Methods 0.000 description 4
• 239000007924 injection Substances 0.000 description 4
• 230000000670 limiting effect Effects 0.000 description 4
• 201000001441 melanoma Diseases 0.000 description 4
• 125000002950 monocyclic group Chemical group 0.000 description 4
• 239000005022 packaging material Substances 0.000 description 4
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
• 229920000642 polymer Polymers 0.000 description 4
• 238000002360 preparation method Methods 0.000 description 4
• 239000003755 preservative agent Substances 0.000 description 4
• 230000008569 process Effects 0.000 description 4
• 230000000069 prophylactic effect Effects 0.000 description 4
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 4
• 230000009467 reduction Effects 0.000 description 4
• 229960004641 rituximab Drugs 0.000 description 4
• 235000019698 starch Nutrition 0.000 description 4
• 238000007920 subcutaneous administration Methods 0.000 description 4
• 239000005720 sucrose Substances 0.000 description 4
• 239000000829 suppository Substances 0.000 description 4
• 208000024891 symptom Diseases 0.000 description 4
• 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 4
• 125000001544 thienyl group Chemical group 0.000 description 4
• HHFBDROWDBDFBR-UHFFFAOYSA-N 4-[[9-chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC1=NC=C(CN=C(C=2C3=CC=C(Cl)C=2)C=2C(=CC=CC=2F)F)C3=N1 HHFBDROWDBDFBR-UHFFFAOYSA-N 0.000 description 3
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 3
• 102000003989 Aurora kinases Human genes 0.000 description 3
• 108090000433 Aurora kinases Proteins 0.000 description 3
• 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 3
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 3
• 102000004506 Blood Proteins Human genes 0.000 description 3
• 108010017384 Blood Proteins Proteins 0.000 description 3
• 206010055113 Breast cancer metastatic Diseases 0.000 description 3
• 239000004215 Carbon black (E152) Substances 0.000 description 3
• 108091060290 Chromatid Proteins 0.000 description 3
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
• 208000032612 Glial tumor Diseases 0.000 description 3
• 206010018338 Glioma Diseases 0.000 description 3
• 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 3
• 241000282412 Homo Species 0.000 description 3
• 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 3
• 241000124008 Mammalia Species 0.000 description 3
• 241000699660 Mus musculus Species 0.000 description 3
• 241001467552 Mycobacterium bovis BCG Species 0.000 description 3
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
• 108091000080 Phosphotransferase Proteins 0.000 description 3
• 208000026149 Primary peritoneal carcinoma Diseases 0.000 description 3
• 208000009527 Refractory anemia Diseases 0.000 description 3
• 208000033501 Refractory anemia with excess blasts Diseases 0.000 description 3
• 206010072684 Refractory cytopenia with unilineage dysplasia Diseases 0.000 description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
• 239000004480 active ingredient Substances 0.000 description 3
• 125000003342 alkenyl group Chemical group 0.000 description 3
• 239000003098 androgen Substances 0.000 description 3
• 208000036878 aneuploidy Diseases 0.000 description 3
• 231100001075 aneuploidy Toxicity 0.000 description 3
• 230000000340 anti-metabolite Effects 0.000 description 3
• 229940100197 antimetabolite Drugs 0.000 description 3
• 125000006615 aromatic heterocyclic group Chemical group 0.000 description 3
• 125000005160 aryl oxy alkyl group Chemical group 0.000 description 3
• 125000004429 atom Chemical group 0.000 description 3
• 229960000190 bacillus calmette–guérin vaccine Drugs 0.000 description 3
• 239000002585 base Substances 0.000 description 3
• 125000002619 bicyclic group Chemical group 0.000 description 3
• 239000011230 binding agent Substances 0.000 description 3
• 210000000988 bone and bone Anatomy 0.000 description 3
• 210000004556 brain Anatomy 0.000 description 3
• 229940022399 cancer vaccine Drugs 0.000 description 3
• 238000009566 cancer vaccine Methods 0.000 description 3
• 210000003793 centrosome Anatomy 0.000 description 3
• 210000004756 chromatid Anatomy 0.000 description 3
• 238000011284 combination treatment Methods 0.000 description 3
• 125000004122 cyclic group Chemical group 0.000 description 3
• 231100000517 death Toxicity 0.000 description 3
• 230000001934 delay Effects 0.000 description 3
• 235000014113 dietary fatty acids Nutrition 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• 239000000839 emulsion Substances 0.000 description 3
• 235000019441 ethanol Nutrition 0.000 description 3
• 238000002474 experimental method Methods 0.000 description 3
• 239000000194 fatty acid Substances 0.000 description 3
• 229930195729 fatty acid Natural products 0.000 description 3
• 239000000945 filler Substances 0.000 description 3
• 238000009472 formulation Methods 0.000 description 3
• 210000003128 head Anatomy 0.000 description 3
• 230000036541 health Effects 0.000 description 3
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 3
• 150000002431 hydrogen Chemical group 0.000 description 3
• 238000002513 implantation Methods 0.000 description 3
• 238000001802 infusion Methods 0.000 description 3
• 229940090044 injection Drugs 0.000 description 3
• 238000010253 intravenous injection Methods 0.000 description 3
• 210000003734 kidney Anatomy 0.000 description 3
• 239000007788 liquid Substances 0.000 description 3
• 210000004185 liver Anatomy 0.000 description 3
• 235000019359 magnesium stearate Nutrition 0.000 description 3
• 230000001404 mediated effect Effects 0.000 description 3
• 239000002207 metabolite Substances 0.000 description 3
• 230000031864 metaphase Effects 0.000 description 3
• 208000037819 metastatic cancer Diseases 0.000 description 3
• 208000011575 metastatic malignant neoplasm Diseases 0.000 description 3
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
• 208000016586 myelodysplastic syndrome with excess blasts Diseases 0.000 description 3
• 238000011580 nude mouse model Methods 0.000 description 3
• 239000003921 oil Substances 0.000 description 3
• 235000019198 oils Nutrition 0.000 description 3
• 210000000056 organ Anatomy 0.000 description 3
• 230000002018 overexpression Effects 0.000 description 3
• 230000036961 partial effect Effects 0.000 description 3
• 208000033808 peripheral neuropathy Diseases 0.000 description 3
• 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 3
• 102000020233 phosphotransferase Human genes 0.000 description 3
• 125000003367 polycyclic group Chemical group 0.000 description 3
• 230000002829 reductive effect Effects 0.000 description 3
• 239000008247 solid mixture Substances 0.000 description 3
• 239000007921 spray Substances 0.000 description 3
• 239000011593 sulfur Substances 0.000 description 3
• 230000004083 survival effect Effects 0.000 description 3
• 230000002459 sustained effect Effects 0.000 description 3
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 3
• 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 3
• 229960000303 topotecan Drugs 0.000 description 3
• 238000011269 treatment regimen Methods 0.000 description 3
• 239000000080 wetting agent Substances 0.000 description 3
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• VOXBZHOHGGBLCQ-UHFFFAOYSA-N 2-amino-3,7-dihydropurine-6-thione;hydrate Chemical compound O.N1C(N)=NC(=S)C2=C1N=CN2.N1C(N)=NC(=S)C2=C1N=CN2 VOXBZHOHGGBLCQ-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
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
• 229920001817 Agar Polymers 0.000 description 2
• 102100023635 Alpha-fetoprotein Human genes 0.000 description 2
• 241001463143 Auca Species 0.000 description 2
• 102000036365 BRCA1 Human genes 0.000 description 2
• 108700020463 BRCA1 Proteins 0.000 description 2
• 101150072950 BRCA1 gene Proteins 0.000 description 2
• 102000052609 BRCA2 Human genes 0.000 description 2
• 108700020462 BRCA2 Proteins 0.000 description 2
• 108010006654 Bleomycin Proteins 0.000 description 2
• 101150008921 Brca2 gene Proteins 0.000 description 2
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
• 108010022366 Carcinoembryonic Antigen Proteins 0.000 description 2
• 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 2
• 201000009030 Carcinoma Diseases 0.000 description 2
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
• 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 2
• 229920000858 Cyclodextrin Polymers 0.000 description 2
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 2
• 230000007018 DNA scission Effects 0.000 description 2
• 230000006820 DNA synthesis Effects 0.000 description 2
• 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 2
• 102000004190 Enzymes Human genes 0.000 description 2
• 108090000790 Enzymes Proteins 0.000 description 2
• 201000001342 Fallopian tube cancer Diseases 0.000 description 2
• 208000013452 Fallopian tube neoplasm Diseases 0.000 description 2
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
• 108010010803 Gelatin Proteins 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
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
• 208000012766 Growth delay Diseases 0.000 description 2
• 239000004705 High-molecular-weight polyethylene Substances 0.000 description 2
• 208000017604 Hodgkin disease Diseases 0.000 description 2
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 2
• 102000014150 Interferons Human genes 0.000 description 2
• 108010050904 Interferons Proteins 0.000 description 2
• 102000013462 Interleukin-12 Human genes 0.000 description 2
• 108010065805 Interleukin-12 Proteins 0.000 description 2
• 102000004388 Interleukin-4 Human genes 0.000 description 2
• 108090000978 Interleukin-4 Proteins 0.000 description 2
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
• 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 2
• 206010025323 Lymphomas Diseases 0.000 description 2
• 206010027406 Mesothelioma Diseases 0.000 description 2
• 201000003793 Myelodysplastic syndrome Diseases 0.000 description 2
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 2
• 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 2
• 206010029260 Neuroblastoma Diseases 0.000 description 2
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
• 102000007999 Nuclear Proteins Human genes 0.000 description 2
• 108010089610 Nuclear Proteins Proteins 0.000 description 2
• 108700020796 Oncogene Proteins 0.000 description 2
• 208000007571 Ovarian Epithelial Carcinoma Diseases 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 102000007066 Prostate-Specific Antigen Human genes 0.000 description 2
• 108010072866 Prostate-Specific Antigen Proteins 0.000 description 2
• 102000001253 Protein Kinase Human genes 0.000 description 2
• 201000004681 Psoriasis Diseases 0.000 description 2
• 241000700159 Rattus Species 0.000 description 2
• 206010038270 Refractory anaemia with an excess of blasts Diseases 0.000 description 2
• 208000032411 Refractory with Excess of Blasts Anemia Diseases 0.000 description 2
• 241000283984 Rodentia Species 0.000 description 2
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
• NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
• 208000024770 Thyroid neoplasm Diseases 0.000 description 2
• 102000007537 Type II DNA Topoisomerases Human genes 0.000 description 2
• 108010046308 Type II DNA Topoisomerases Proteins 0.000 description 2
• 102000040856 WT1 Human genes 0.000 description 2
• 108700020467 WT1 Proteins 0.000 description 2
• 241000269370 Xenopus <genus> Species 0.000 description 2
• 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 2
• RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
• 239000013543 active substance Substances 0.000 description 2
• 230000002411 adverse Effects 0.000 description 2
• 239000008272 agar Substances 0.000 description 2
• 229940023476 agar Drugs 0.000 description 2
• 235000010419 agar Nutrition 0.000 description 2
• 239000000783 alginic acid Substances 0.000 description 2
• 229960001126 alginic acid Drugs 0.000 description 2
• 150000004781 alginic acids Chemical class 0.000 description 2
• 108010026331 alpha-Fetoproteins Proteins 0.000 description 2
• 229940024606 amino acid Drugs 0.000 description 2
• 150000001413 amino acids Chemical class 0.000 description 2
• 238000004458 analytical method Methods 0.000 description 2
• 230000031016 anaphase Effects 0.000 description 2
• 230000033115 angiogenesis Effects 0.000 description 2
• 229940045799 anthracyclines and related substance Drugs 0.000 description 2
• 239000003242 anti bacterial agent Substances 0.000 description 2
• 230000002927 anti-mitotic effect Effects 0.000 description 2
• 229940088710 antibiotic agent Drugs 0.000 description 2
• 230000006907 apoptotic process Effects 0.000 description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 2
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
• SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
• 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 2
• 229920002988 biodegradable polymer Polymers 0.000 description 2
• 239000004621 biodegradable polymer Substances 0.000 description 2
• 229960001561 bleomycin Drugs 0.000 description 2
• OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound 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=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 2
• 150000001649 bromium compounds Chemical class 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 239000006172 buffering agent Substances 0.000 description 2
• 235000019437 butane-1,3-diol Nutrition 0.000 description 2
• 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 2
• 239000001768 carboxy methyl cellulose Substances 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 230000025084 cell cycle arrest Effects 0.000 description 2
• 230000023359 cell cycle switching, meiotic to mitotic cell cycle Effects 0.000 description 2
• 125000001309 chloro group Chemical group Cl* 0.000 description 2
• 230000024321 chromosome segregation Effects 0.000 description 2
• 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 2
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
• 229960004316 cisplatin Drugs 0.000 description 2
• 229940110456 cocoa butter Drugs 0.000 description 2
• 235000019868 cocoa butter Nutrition 0.000 description 2
• 239000000470 constituent Substances 0.000 description 2
• 230000001276 controlling effect Effects 0.000 description 2
• 235000012343 cottonseed oil Nutrition 0.000 description 2
• 229940097362 cyclodextrins Drugs 0.000 description 2
• 230000021953 cytokinesis Effects 0.000 description 2
• 230000001086 cytosolic effect Effects 0.000 description 2
• 230000034994 death Effects 0.000 description 2
• 230000002950 deficient Effects 0.000 description 2
• 230000002939 deleterious effect Effects 0.000 description 2
• 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 2
• ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 2
• 235000019797 dipotassium phosphate Nutrition 0.000 description 2
• 229910000396 dipotassium phosphate Inorganic materials 0.000 description 2
• BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• 229960004679 doxorubicin Drugs 0.000 description 2
• 239000008298 dragée Substances 0.000 description 2
• 230000001804 emulsifying effect Effects 0.000 description 2
• 239000002158 endotoxin Substances 0.000 description 2
• 239000002702 enteric coating Substances 0.000 description 2
• 238000009505 enteric coating Methods 0.000 description 2
• 229940088598 enzyme Drugs 0.000 description 2
• 150000002148 esters Chemical class 0.000 description 2
• MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 150000004665 fatty acids Chemical class 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 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 2
• 229960002949 fluorouracil Drugs 0.000 description 2
• 210000001035 gastrointestinal tract Anatomy 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• 239000008103 glucose Substances 0.000 description 2
• 229910052736 halogen Inorganic materials 0.000 description 2
• 125000001475 halogen functional group Chemical group 0.000 description 2
• 150000002367 halogens Chemical class 0.000 description 2
• 201000011066 hemangioma Diseases 0.000 description 2
• 229940022353 herceptin Drugs 0.000 description 2
• 150000002430 hydrocarbons Chemical class 0.000 description 2
• 206010020718 hyperplasia Diseases 0.000 description 2
• 125000002883 imidazolyl group Chemical group 0.000 description 2
• 230000002519 immonomodulatory effect Effects 0.000 description 2
• 239000002955 immunomodulating agent Substances 0.000 description 2
• 238000000099 in vitro assay Methods 0.000 description 2
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 2
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 2
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 2
• 125000001041 indolyl group Chemical group 0.000 description 2
• 230000000977 initiatory effect Effects 0.000 description 2
• 239000007972 injectable composition Substances 0.000 description 2
• 230000003993 interaction Effects 0.000 description 2
• 229940117681 interleukin-12 Drugs 0.000 description 2
• 229940028885 interleukin-4 Drugs 0.000 description 2
• 150000004694 iodide salts Chemical class 0.000 description 2
• 150000002500 ions Chemical class 0.000 description 2
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 2
• 125000005956 isoquinolyl group Chemical group 0.000 description 2
• 239000007951 isotonicity adjuster Substances 0.000 description 2
• 239000011159 matrix material Substances 0.000 description 2
• 238000005259 measurement Methods 0.000 description 2
• 238000010946 mechanistic model Methods 0.000 description 2
• 239000004530 micro-emulsion Substances 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 230000035772 mutation Effects 0.000 description 2
• 208000025113 myeloid leukemia Diseases 0.000 description 2
• 210000003739 neck Anatomy 0.000 description 2
• 210000000653 nervous system Anatomy 0.000 description 2
• 210000000440 neutrophil Anatomy 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 239000000346 nonvolatile oil Substances 0.000 description 2
• 102000039446 nucleic acids Human genes 0.000 description 2
• 108020004707 nucleic acids Proteins 0.000 description 2
• 150000007523 nucleic acids Chemical class 0.000 description 2
• 239000004006 olive oil Substances 0.000 description 2
• 229910052760 oxygen Inorganic materials 0.000 description 2
• 239000001301 oxygen Substances 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• 239000002304 perfume Substances 0.000 description 2
• 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 2
• 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 2
• 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 2
• 235000021317 phosphate Nutrition 0.000 description 2
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• 108090000765 processed proteins & peptides Proteins 0.000 description 2
• 238000004393 prognosis Methods 0.000 description 2
• 238000011321 prophylaxis Methods 0.000 description 2
• 229960004063 propylene glycol Drugs 0.000 description 2
• 108060006633 protein kinase Proteins 0.000 description 2
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 2
• 125000005493 quinolyl group Chemical group 0.000 description 2
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 2
• 102000005962 receptors Human genes 0.000 description 2
• 108020003175 receptors Proteins 0.000 description 2
• 210000000664 rectum Anatomy 0.000 description 2
• 208000037803 restenosis Diseases 0.000 description 2
• 238000005204 segregation Methods 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• 239000008159 sesame oil Substances 0.000 description 2
• 235000011803 sesame oil Nutrition 0.000 description 2
• 229910000029 sodium carbonate Inorganic materials 0.000 description 2
• 235000017550 sodium carbonate Nutrition 0.000 description 2
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
• 239000008107 starch Substances 0.000 description 2
• 150000003431 steroids Chemical class 0.000 description 2
• 208000003265 stomatitis Diseases 0.000 description 2
• 238000003860 storage Methods 0.000 description 2
• 230000001629 suppression Effects 0.000 description 2
• 239000004094 surface-active agent Substances 0.000 description 2
• 239000000375 suspending agent Substances 0.000 description 2
• 239000003765 sweetening agent Substances 0.000 description 2
• 239000006188 syrup Substances 0.000 description 2
• 235000020357 syrup Nutrition 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
• 230000008685 targeting Effects 0.000 description 2
• 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 2
• 230000002381 testicular Effects 0.000 description 2
• 238000012360 testing method Methods 0.000 description 2
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 2
• 230000004797 therapeutic response Effects 0.000 description 2
• 230000008719 thickening Effects 0.000 description 2
• 239000002562 thickening agent Substances 0.000 description 2
• 201000002510 thyroid cancer Diseases 0.000 description 2
• 229960003087 tioguanine Drugs 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• 230000005747 tumor angiogenesis Effects 0.000 description 2
• 230000004862 vasculogenesis Effects 0.000 description 2
• LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
• XMAYWYJOQHXEEK-OZXSUGGESA-N (2R,4S)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-OZXSUGGESA-N 0.000 description 1
• JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
• DEQANNDTNATYII-OULOTJBUSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-16-benzyl-n-[(2r,3r)-1,3-dihydroxybutan-2-yl]-7-[(1r)-1-hydroxyethyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxa Chemical compound C([C@@H](N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@H](CO)[C@H](O)C)C1=CC=CC=C1 DEQANNDTNATYII-OULOTJBUSA-N 0.000 description 1
• FPVKHBSQESCIEP-UHFFFAOYSA-N (8S)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol Natural products C1C(O)C(CO)OC1N1C(NC=NCC2O)=C2N=C1 FPVKHBSQESCIEP-UHFFFAOYSA-N 0.000 description 1
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 1
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
• FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-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
• 229940058015 1,3-butylene glycol Drugs 0.000 description 1
• VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical class CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
• VUQPJRPDRDVQMN-UHFFFAOYSA-N 1-chlorooctadecane Chemical class CCCCCCCCCCCCCCCCCCCl VUQPJRPDRDVQMN-UHFFFAOYSA-N 0.000 description 1
• VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
• KRQUFUKTQHISJB-YYADALCUSA-N 2-[(E)-N-[2-(4-chlorophenoxy)propoxy]-C-propylcarbonimidoyl]-3-hydroxy-5-(thian-3-yl)cyclohex-2-en-1-one Chemical compound CCC\C(=N/OCC(C)OC1=CC=C(Cl)C=C1)C1=C(O)CC(CC1=O)C1CCCSC1 KRQUFUKTQHISJB-YYADALCUSA-N 0.000 description 1
• 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
• WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical class BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-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
• ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
• XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
• AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin 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-VTZDEGQISA-N 0.000 description 1
• 125000002471 4H-quinolizinyl group Chemical group C=1(C=CCN2C=CC=CC12)* 0.000 description 1
• IDPUKCWIGUEADI-UHFFFAOYSA-N 5-[bis(2-chloroethyl)amino]uracil Chemical compound ClCCN(CCCl)C1=CNC(=O)NC1=O IDPUKCWIGUEADI-UHFFFAOYSA-N 0.000 description 1
• WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 1
• MMRCWWRFYLZGAE-ZBZRSYSASA-N 533u947v6q Chemical compound 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 MMRCWWRFYLZGAE-ZBZRSYSASA-N 0.000 description 1
• FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
• VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 description 1
• 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 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• 101150095401 AURKA gene Proteins 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• 206010073128 Anaplastic oligodendroglioma Diseases 0.000 description 1
• 235000003276 Apios tuberosa Nutrition 0.000 description 1
• 244000105624 Arachis hypogaea Species 0.000 description 1
• 235000010777 Arachis hypogaea Nutrition 0.000 description 1
• 235000010744 Arachis villosulicarpa Nutrition 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 102000015790 Asparaginase Human genes 0.000 description 1
• 108010024976 Asparaginase Proteins 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 206010003571 Astrocytoma Diseases 0.000 description 1
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
• 208000003950 B-cell lymphoma Diseases 0.000 description 1
• 208000028564 B-cell non-Hodgkin lymphoma Diseases 0.000 description 1
• 208000004860 Blast Crisis Diseases 0.000 description 1
• 206010005949 Bone cancer Diseases 0.000 description 1
• 206010065553 Bone marrow failure Diseases 0.000 description 1
• 208000018084 Bone neoplasm 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
• FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
• 208000037051 Chromosomal Instability 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
• 206010048832 Colon adenoma Diseases 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 101001124881 Cricetulus griseus Peroxiredoxin-1 Proteins 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
• 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 1
• 230000004543 DNA replication Effects 0.000 description 1
• 108010092160 Dactinomycin Proteins 0.000 description 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 206010012735 Diarrhoea Diseases 0.000 description 1
• 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
• 206010061818 Disease progression Diseases 0.000 description 1
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 206010014967 Ependymoma Diseases 0.000 description 1
• HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 1
• 102000003951 Erythropoietin Human genes 0.000 description 1
• 108090000394 Erythropoietin Proteins 0.000 description 1
• 239000001856 Ethyl cellulose Substances 0.000 description 1
• ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 239000004606 Fillers/Extenders Substances 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
• 230000010190 G1 phase Effects 0.000 description 1
• 230000037057 G1 phase arrest Effects 0.000 description 1
• 230000010337 G2 phase Effects 0.000 description 1
• 206010059024 Gastrointestinal toxicity Diseases 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Polymers OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
• 108010069236 Goserelin Proteins 0.000 description 1
• 206010053759 Growth retardation Diseases 0.000 description 1
• 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
• 108010033040 Histones Proteins 0.000 description 1
• 102000006947 Histones Human genes 0.000 description 1
• 101000578784 Homo sapiens Melanoma antigen recognized by T-cells 1 Proteins 0.000 description 1
• 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
• 101000691459 Homo sapiens Serine/threonine-protein kinase N2 Proteins 0.000 description 1
• 102000008100 Human Serum Albumin Human genes 0.000 description 1
• 108091006905 Human Serum Albumin Proteins 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-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
• 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 1
• 102000015696 Interleukins Human genes 0.000 description 1
• 108010063738 Interleukins Proteins 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
• 229930182816 L-glutamine Natural products 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
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• 108010000817 Leuprolide Proteins 0.000 description 1
• HLFSDGLLUJUHTE-SNVBAGLBSA-N Levamisole Chemical compound C1([C@H]2CN3CCSC3=N2)=CC=CC=C1 HLFSDGLLUJUHTE-SNVBAGLBSA-N 0.000 description 1
• 238000003657 Likelihood-ratio test Methods 0.000 description 1
• GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 1
• 208000028018 Lymphocytic leukaemia Diseases 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• 240000003183 Manihot esculenta Species 0.000 description 1
• 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 1
• 238000007476 Maximum Likelihood Methods 0.000 description 1
• 102100028389 Melanoma antigen recognized by T-cells 1 Human genes 0.000 description 1
• 206010027480 Metastatic malignant melanoma Diseases 0.000 description 1
• 206010050513 Metastatic renal cell carcinoma Diseases 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 description 1
• 206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
• 206010028813 Nausea Diseases 0.000 description 1
• 201000004404 Neurofibroma Diseases 0.000 description 1
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
• 108091005461 Nucleic proteins Proteins 0.000 description 1
• 108010016076 Octreotide Proteins 0.000 description 1
• 240000007817 Olea europaea Species 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
• 201000010133 Oligodendroglioma Diseases 0.000 description 1
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
• 241000282577 Pan troglodytes Species 0.000 description 1
• 241001631646 Papillomaviridae Species 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 239000004264 Petrolatum Substances 0.000 description 1
• 229920002732 Polyanhydride Polymers 0.000 description 1
• 229920000954 Polyglycolide Polymers 0.000 description 1
• 229920001710 Polyorthoester Polymers 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• 102000007327 Protamines Human genes 0.000 description 1
• 108010007568 Protamines Proteins 0.000 description 1
• 108010029485 Protein Isoforms Proteins 0.000 description 1
• 102000001708 Protein Isoforms Human genes 0.000 description 1
• YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 description 1
• 206010037660 Pyrexia Diseases 0.000 description 1
• 201000000582 Retinoblastoma Diseases 0.000 description 1
• 235000004443 Ricinus communis Nutrition 0.000 description 1
• 230000018199 S phase Effects 0.000 description 1
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
• 235000019485 Safflower oil Nutrition 0.000 description 1
• 206010039491 Sarcoma Diseases 0.000 description 1
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
• 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
• 208000021712 Soft tissue sarcoma Diseases 0.000 description 1
• 244000061456 Solanum tuberosum Species 0.000 description 1
• 235000002595 Solanum tuberosum Nutrition 0.000 description 1
• 102000005157 Somatostatin Human genes 0.000 description 1
• 108010056088 Somatostatin Proteins 0.000 description 1
• 206010041349 Somnolence Diseases 0.000 description 1
• 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 description 1
• SSZBUIDZHHWXNJ-UHFFFAOYSA-N Stearinsaeure-hexadecylester Natural products CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC SSZBUIDZHHWXNJ-UHFFFAOYSA-N 0.000 description 1
• 238000000692 Student's t-test Methods 0.000 description 1
• 206010042971 T-cell lymphoma Diseases 0.000 description 1
• 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
• 210000001744 T-lymphocyte Anatomy 0.000 description 1
• 241001116500 Taxus Species 0.000 description 1
• 208000035199 Tetraploidy Diseases 0.000 description 1
• ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
• FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
• 102000004243 Tubulin Human genes 0.000 description 1
• 108090000704 Tubulin Proteins 0.000 description 1
• 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 1
• 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 1
• 102100039094 Tyrosinase Human genes 0.000 description 1
• 108060008724 Tyrosinase Proteins 0.000 description 1
• 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 1
• 229940122803 Vinca alkaloid Drugs 0.000 description 1
• 206010047700 Vomiting Diseases 0.000 description 1
• 231100000480 WST assay Toxicity 0.000 description 1
• 101150084041 WT1 gene Proteins 0.000 description 1
• 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
• 240000008042 Zea mays Species 0.000 description 1
• 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
• 239000001089 [(2R)-oxolan-2-yl]methanol Substances 0.000 description 1
• 239000002250 absorbent Substances 0.000 description 1
• 230000002745 absorbent Effects 0.000 description 1
• 239000003655 absorption accelerator Substances 0.000 description 1
• 229940022663 acetate Drugs 0.000 description 1
• 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 1
• 239000002253 acid Substances 0.000 description 1
• RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D 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)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 208000009956 adenocarcinoma Diseases 0.000 description 1
• WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
• 210000000577 adipose tissue Anatomy 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 108700025316 aldesleukin Proteins 0.000 description 1
• 229960005310 aldesleukin Drugs 0.000 description 1
• 229940072056 alginate Drugs 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 125000003545 alkoxy group Chemical group 0.000 description 1
• 150000001350 alkyl halides Chemical class 0.000 description 1
• 125000000304 alkynyl group Chemical group 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• 230000000735 allogeneic effect Effects 0.000 description 1
• AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
• 229960000473 altretamine Drugs 0.000 description 1
• WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
• 229940063655 aluminum stearate Drugs 0.000 description 1
• 230000037354 amino acid metabolism Effects 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
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 206010002022 amyloidosis Diseases 0.000 description 1
• 206010002224 anaplastic astrocytoma Diseases 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
• 229940030486 androgens Drugs 0.000 description 1
• 239000005557 antagonist Substances 0.000 description 1
• RGHILYZRVFRRNK-UHFFFAOYSA-N anthracene-1,2-dione Chemical compound C1=CC=C2C=C(C(C(=O)C=C3)=O)C3=CC2=C1 RGHILYZRVFRRNK-UHFFFAOYSA-N 0.000 description 1
• 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
• 230000002280 anti-androgenic effect Effects 0.000 description 1
• 229940046836 anti-estrogen Drugs 0.000 description 1
• 230000001833 anti-estrogenic effect Effects 0.000 description 1
• 230000001028 anti-proliverative effect Effects 0.000 description 1
• 239000000051 antiandrogen Substances 0.000 description 1
• 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
• 238000011319 anticancer therapy Methods 0.000 description 1
• 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 1
• 229940045985 antineoplastic platinum compound Drugs 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 238000003782 apoptosis assay Methods 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 239000003886 aromatase inhibitor Substances 0.000 description 1
• 229940046844 aromatase inhibitors Drugs 0.000 description 1
• 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
• 238000003491 array Methods 0.000 description 1
• 229960003272 asparaginase Drugs 0.000 description 1
• DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical compound [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• 230000035578 autophosphorylation Effects 0.000 description 1
• 150000001541 aziridines Chemical class 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 239000000440 bentonite Substances 0.000 description 1
• 229910000278 bentonite Inorganic materials 0.000 description 1
• SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
• 229940077388 benzenesulfonate Drugs 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• 229940050390 benzoate Drugs 0.000 description 1
• 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 229960002903 benzyl benzoate Drugs 0.000 description 1
• XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
• 229960000997 bicalutamide Drugs 0.000 description 1
• 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 230000036760 body temperature Effects 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 210000000621 bronchi Anatomy 0.000 description 1
• 229960002092 busulfan Drugs 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 235000010216 calcium carbonate Nutrition 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
• 239000008116 calcium stearate Substances 0.000 description 1
• 235000013539 calcium stearate Nutrition 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
• 230000005907 cancer growth Effects 0.000 description 1
• 125000002837 carbocyclic group Chemical group 0.000 description 1
• 125000004452 carbocyclyl group Chemical group 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 229960005243 carmustine Drugs 0.000 description 1
• 210000000845 cartilage Anatomy 0.000 description 1
• 239000004359 castor oil Substances 0.000 description 1
• 108020001778 catalytic domains Proteins 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 230000012820 cell cycle checkpoint Effects 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 230000003915 cell function Effects 0.000 description 1
• 230000003833 cell viability Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 229920002301 cellulose acetate Polymers 0.000 description 1
• 210000003679 cervix uteri Anatomy 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• 239000013522 chelant Substances 0.000 description 1
• 238000000546 chi-square test Methods 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
• 229910052801 chlorine Inorganic materials 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
• 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
• 230000002759 chromosomal effect Effects 0.000 description 1
• 229960002436 cladribine Drugs 0.000 description 1
• 239000004927 clay Substances 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 239000008119 colloidal silica Substances 0.000 description 1
• 208000029742 colonic neoplasm Diseases 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 230000000295 complement effect Effects 0.000 description 1
• 230000001010 compromised effect Effects 0.000 description 1
• 239000012050 conventional carrier Substances 0.000 description 1
• 235000005822 corn Nutrition 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
• 230000002596 correlated effect Effects 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 125000000392 cycloalkenyl group Chemical group 0.000 description 1
• 125000000753 cycloalkyl group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 229960004397 cyclophosphamide Drugs 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 229960000684 cytarabine Drugs 0.000 description 1
• 229960003901 dacarbazine Drugs 0.000 description 1
• 229960000640 dactinomycin Drugs 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• 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 1
• 229960000975 daunorubicin Drugs 0.000 description 1
• 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 description 1
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• 150000008050 dialkyl sulfates Chemical class 0.000 description 1
• 125000002576 diazepinyl group Chemical group N1N=C(C=CC=C1)* 0.000 description 1
• NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
• 229940038472 dicalcium phosphate Drugs 0.000 description 1
• 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• FSBVERYRVPGNGG-UHFFFAOYSA-N dimagnesium dioxido-bis[[oxido(oxo)silyl]oxy]silane hydrate Chemical compound O.[Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O FSBVERYRVPGNGG-UHFFFAOYSA-N 0.000 description 1
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
• 230000003292 diminished effect Effects 0.000 description 1
• 125000000532 dioxanyl group Chemical group 0.000 description 1
• 125000005879 dioxolanyl group Chemical group 0.000 description 1
• GAFRWLVTHPVQGK-UHFFFAOYSA-N dipentyl sulfate Chemical class CCCCCOS(=O)(=O)OCCCCC GAFRWLVTHPVQGK-UHFFFAOYSA-N 0.000 description 1
• 230000005750 disease progression Effects 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 125000000567 diterpene group Chemical group 0.000 description 1
• 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
• 229940043264 dodecyl sulfate Drugs 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 239000003221 ear drop Substances 0.000 description 1
• 229940047652 ear drops Drugs 0.000 description 1
• 239000003792 electrolyte Substances 0.000 description 1
• 230000002357 endometrial effect Effects 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• 239000002662 enteric coated tablet Substances 0.000 description 1
• 229960001904 epirubicin Drugs 0.000 description 1
• 229940105423 erythropoietin Drugs 0.000 description 1
• 210000003238 esophagus Anatomy 0.000 description 1
• 239000003687 estradiol congener Substances 0.000 description 1
• 229940011871 estrogen Drugs 0.000 description 1
• 239000000262 estrogen Substances 0.000 description 1
• 239000000328 estrogen antagonist Substances 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 229940093499 ethyl acetate Drugs 0.000 description 1
• 235000019325 ethyl cellulose Nutrition 0.000 description 1
• 229920001249 ethyl cellulose Polymers 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 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
• 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 description 1
• 229960005420 etoposide Drugs 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 230000031376 exit from mitosis Effects 0.000 description 1
• 239000003889 eye drop Substances 0.000 description 1
• 229940012356 eye drops Drugs 0.000 description 1
• 235000019197 fats Nutrition 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 229960000961 floxuridine Drugs 0.000 description 1
• 229960005304 fludarabine phosphate Drugs 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
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 125000001207 fluorophenyl group Chemical group 0.000 description 1
• 229960002074 flutamide Drugs 0.000 description 1
• MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
• 230000004907 flux Effects 0.000 description 1
• VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 description 1
• 235000008191 folinic acid Nutrition 0.000 description 1
• 239000011672 folinic acid Substances 0.000 description 1
• 230000003325 follicular Effects 0.000 description 1
• 201000003444 follicular lymphoma Diseases 0.000 description 1
• 235000013305 food Nutrition 0.000 description 1
• 150000002270 gangliosides Chemical class 0.000 description 1
• 231100000414 gastrointestinal toxicity Toxicity 0.000 description 1
• 229960005277 gemcitabine Drugs 0.000 description 1
• 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 1
• 208000005017 glioblastoma Diseases 0.000 description 1
• 235000001727 glucose Nutrition 0.000 description 1
• 125000005456 glyceride group Chemical group 0.000 description 1
• YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
• SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
• 150000002334 glycols Chemical class 0.000 description 1
• 229960003690 goserelin acetate Drugs 0.000 description 1
• 210000003714 granulocyte Anatomy 0.000 description 1
• 230000009036 growth inhibition Effects 0.000 description 1
• 231100000001 growth retardation Toxicity 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 125000000262 haloalkenyl group Chemical group 0.000 description 1
• 125000004438 haloalkoxy group Chemical group 0.000 description 1
• 125000001188 haloalkyl group Chemical group 0.000 description 1
• 201000000459 head and neck squamous cell carcinoma Diseases 0.000 description 1
• 230000011132 hemopoiesis Effects 0.000 description 1
• MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
• 125000004415 heterocyclylalkyl group Chemical group 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
• FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• 102000044614 human AURKA Human genes 0.000 description 1
• 239000003906 humectant Substances 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 229960000908 idarubicin 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
• 238000003384 imaging method Methods 0.000 description 1
• 230000036737 immune function Effects 0.000 description 1
• 210000000987 immune system Anatomy 0.000 description 1
• 238000009169 immunotherapy Methods 0.000 description 1
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
• 230000006882 induction of apoptosis Effects 0.000 description 1
• 229940102223 injectable solution Drugs 0.000 description 1
• 229940102213 injectable suspension Drugs 0.000 description 1
• 230000002452 interceptive effect Effects 0.000 description 1
• 229940079322 interferon Drugs 0.000 description 1
• 229940047124 interferons Drugs 0.000 description 1
• 229940047122 interleukins Drugs 0.000 description 1
• 238000007917 intracranial administration Methods 0.000 description 1
• 210000003228 intrahepatic bile duct Anatomy 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000010255 intramuscular injection Methods 0.000 description 1
• 239000007927 intramuscular injection Substances 0.000 description 1
• 238000007919 intrasynovial administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• 230000002427 irreversible effect Effects 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
• 229960004125 ketoconazole Drugs 0.000 description 1
• 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 1
• 208000022013 kidney Wilms tumor Diseases 0.000 description 1
• 210000000244 kidney pelvis Anatomy 0.000 description 1
• 210000002415 kinetochore Anatomy 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 229960001691 leucovorin Drugs 0.000 description 1
• 230000021633 leukocyte mediated immunity Effects 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
• 229960001614 levamisole Drugs 0.000 description 1
• 238000012417 linear regression Methods 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 229920006008 lipopolysaccharide Polymers 0.000 description 1
• 239000002502 liposome Substances 0.000 description 1
• 239000006194 liquid suspension Substances 0.000 description 1
• 229960002247 lomustine Drugs 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 201000005249 lung adenocarcinoma Diseases 0.000 description 1
• 208000003747 lymphoid leukemia Diseases 0.000 description 1
• 239000006166 lysate Substances 0.000 description 1
• VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
• 239000000347 magnesium hydroxide Substances 0.000 description 1
• 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
• 235000012254 magnesium hydroxide Nutrition 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 239000000391 magnesium silicate Substances 0.000 description 1
• 235000019793 magnesium trisilicate Nutrition 0.000 description 1
• 229940099273 magnesium trisilicate Drugs 0.000 description 1
• 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 230000003211 malignant effect Effects 0.000 description 1
• 210000004962 mammalian cell Anatomy 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 230000035800 maturation Effects 0.000 description 1
• 210000003519 mature b lymphocyte Anatomy 0.000 description 1
• 235000012054 meals Nutrition 0.000 description 1
• 230000010534 mechanism of action Effects 0.000 description 1
• 229960004961 mechlorethamine Drugs 0.000 description 1
• HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 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
• 229960004296 megestrol 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
• 239000012528 membrane Substances 0.000 description 1
• 206010027191 meningioma Diseases 0.000 description 1
• GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 230000022339 metaphase plate congression Effects 0.000 description 1
• 230000001394 metastastic effect Effects 0.000 description 1
• 208000021039 metastatic melanoma Diseases 0.000 description 1
• 206010061289 metastatic neoplasm Diseases 0.000 description 1
• 229960000485 methotrexate Drugs 0.000 description 1
• 238000012737 microarray-based gene expression Methods 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 230000008880 microtubule cytoskeleton organization Effects 0.000 description 1
• 230000025090 microtubule depolymerization Effects 0.000 description 1
• VKHAHZOOUSRJNA-GCNJZUOMSA-N mifepristone Chemical compound C1([C@@H]2C3=C4CCC(=O)C=C4CC[C@H]3[C@@H]3CC[C@@]([C@]3(C2)C)(O)C#CC)=CC=C(N(C)C)C=C1 VKHAHZOOUSRJNA-GCNJZUOMSA-N 0.000 description 1
• 229960003248 mifepristone Drugs 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 150000007522 mineralic acids Chemical class 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
• 229960004857 mitomycin Drugs 0.000 description 1
• 230000008600 mitotic progression Effects 0.000 description 1
• CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• 230000000877 morphologic effect Effects 0.000 description 1
• 238000010172 mouse model Methods 0.000 description 1
• 210000000214 mouth Anatomy 0.000 description 1
• 238000012243 multiplex automated genomic engineering Methods 0.000 description 1
• 201000000050 myeloid neoplasm Diseases 0.000 description 1
• 230000003525 myelopoietic effect Effects 0.000 description 1
• 230000002071 myeloproliferative effect Effects 0.000 description 1
• 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• BLCLNMBMMGCOAS-UHFFFAOYSA-N n-[1-[[1-[[1-[[1-[[1-[[1-[[1-[2-[(carbamoylamino)carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amin Chemical compound C1CCC(C(=O)NNC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)C(COC(C)(C)C)NC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 BLCLNMBMMGCOAS-UHFFFAOYSA-N 0.000 description 1
• KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
• 229930014626 natural product Natural products 0.000 description 1
• 230000008693 nausea Effects 0.000 description 1
• 230000017074 necrotic cell death Effects 0.000 description 1
• 230000035407 negative regulation of cell proliferation Effects 0.000 description 1
• 230000009826 neoplastic cell growth Effects 0.000 description 1
• 230000000955 neuroendocrine Effects 0.000 description 1
• 201000011519 neuroendocrine tumor Diseases 0.000 description 1
• 201000001119 neuropathy Diseases 0.000 description 1
• 230000007823 neuropathy Effects 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 229960002653 nilutamide Drugs 0.000 description 1
• XWXYUMMDTVBTOU-UHFFFAOYSA-N nilutamide Chemical compound O=C1C(C)(C)NC(=O)N1C1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 XWXYUMMDTVBTOU-UHFFFAOYSA-N 0.000 description 1
• 150000002829 nitrogen Chemical class 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 231100000344 non-irritating Toxicity 0.000 description 1
• 229960002700 octreotide Drugs 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 231100000590 oncogenic Toxicity 0.000 description 1
• 230000002246 oncogenic effect Effects 0.000 description 1
• 230000006548 oncogenic transformation Effects 0.000 description 1
• 238000011275 oncology therapy Methods 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• 125000000160 oxazolidinyl group Chemical group 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 239000003002 pH adjusting agent Substances 0.000 description 1
• 229940108949 paclitaxel injection Drugs 0.000 description 1
• 210000000496 pancreas Anatomy 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 239000006072 paste Substances 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 229960002340 pentostatin Drugs 0.000 description 1
• FPVKHBSQESCIEP-JQCXWYLXSA-N pentostatin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC[C@H]2O)=C2N=C1 FPVKHBSQESCIEP-JQCXWYLXSA-N 0.000 description 1
• JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
• 229940066842 petrolatum Drugs 0.000 description 1
• 235000019271 petrolatum Nutrition 0.000 description 1
• 239000003208 petroleum Substances 0.000 description 1
• 210000003800 pharynx Anatomy 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• 208000028591 pheochromocytoma Diseases 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
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 230000035479 physiological effects, processes and functions Effects 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 229940075930 picrate Drugs 0.000 description 1
• OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 229950010765 pivalate Drugs 0.000 description 1
• IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
• 230000036470 plasma concentration Effects 0.000 description 1
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
• 150000003058 platinum compounds Chemical class 0.000 description 1
• 229960003171 plicamycin Drugs 0.000 description 1
• 229920000058 polyacrylate Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 239000011736 potassium bicarbonate Substances 0.000 description 1
• 235000015497 potassium bicarbonate Nutrition 0.000 description 1
• 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• 235000011181 potassium carbonates Nutrition 0.000 description 1
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• 235000010241 potassium sorbate Nutrition 0.000 description 1
• 239000004302 potassium sorbate Substances 0.000 description 1
• 229940069338 potassium sorbate Drugs 0.000 description 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 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 230000009290 primary effect Effects 0.000 description 1
• 210000001948 pro-b lymphocyte Anatomy 0.000 description 1
• 229960000624 procarbazine Drugs 0.000 description 1
• CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 1
• 239000000047 product Substances 0.000 description 1
• 239000000583 progesterone congener Substances 0.000 description 1
• 230000005522 programmed cell death Effects 0.000 description 1
• 230000000750 progressive effect Effects 0.000 description 1
• 230000035755 proliferation Effects 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 229950008679 protamine sulfate Drugs 0.000 description 1
• 238000001243 protein synthesis Methods 0.000 description 1
• 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
• 239000002212 purine nucleoside Substances 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• 125000004076 pyridyl group Chemical group 0.000 description 1
• 239000002718 pyrimidine nucleoside Substances 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 125000004929 pyrrolidonyl group Chemical group N1(C(CCC1)=O)* 0.000 description 1
• 125000001422 pyrrolinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 238000011002 quantification Methods 0.000 description 1
• 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
• 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
• 230000005855 radiation Effects 0.000 description 1
• 238000000163 radioactive labelling Methods 0.000 description 1
• 239000002287 radioligand Substances 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 229910052705 radium Inorganic materials 0.000 description 1
• 229960004622 raloxifene Drugs 0.000 description 1
• GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
• 230000000306 recurrent effect Effects 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 238000012827 research and development Methods 0.000 description 1
• 239000003340 retarding agent Substances 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 239000002342 ribonucleoside Substances 0.000 description 1
• 235000005713 safflower oil Nutrition 0.000 description 1
• 239000003813 safflower oil Substances 0.000 description 1
• 108010038379 sargramostim Proteins 0.000 description 1
• 229960002530 sargramostim Drugs 0.000 description 1
• 230000009758 senescence Effects 0.000 description 1
• 150000004760 silicates Chemical class 0.000 description 1
• RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
• 235000012239 silicon dioxide Nutrition 0.000 description 1
• 210000003491 skin Anatomy 0.000 description 1
• 210000000813 small intestine Anatomy 0.000 description 1
• AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 239000001509 sodium citrate Substances 0.000 description 1
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
• 229960000553 somatostatin Drugs 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 239000003549 soybean oil Substances 0.000 description 1
• 235000012424 soybean oil Nutrition 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 230000020347 spindle assembly Effects 0.000 description 1
• 230000007046 spindle assembly involved in mitosis Effects 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
• 238000007619 statistical method Methods 0.000 description 1
• 210000000130 stem cell Anatomy 0.000 description 1
• 239000008223 sterile water Substances 0.000 description 1
• 239000003206 sterilizing agent Substances 0.000 description 1
• 230000007019 strand scission Effects 0.000 description 1
• 229960001052 streptozocin 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
• 230000004960 subcellular localization Effects 0.000 description 1
• 238000010254 subcutaneous injection Methods 0.000 description 1
• 239000007929 subcutaneous injection Substances 0.000 description 1
• 125000003107 substituted aryl group Chemical group 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 150000003871 sulfonates Chemical class 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 238000012353 t test Methods 0.000 description 1
• 229960001603 tamoxifen Drugs 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 230000016853 telophase Effects 0.000 description 1
• 229960001278 teniposide Drugs 0.000 description 1
• YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
• 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
• 150000003536 tetrazoles Chemical class 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 238000011287 therapeutic dose Methods 0.000 description 1
• 231100001274 therapeutic index Toxicity 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000005308 thiazepinyl group Chemical group S1N=C(C=CC=C1)* 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 229960001196 thiotepa Drugs 0.000 description 1
• 210000001685 thyroid gland Anatomy 0.000 description 1
• 230000036962 time dependent Effects 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
• 125000003944 tolyl group Chemical group 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 229960005026 toremifene Drugs 0.000 description 1
• XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 230000001131 transforming effect Effects 0.000 description 1
• 230000001052 transient effect Effects 0.000 description 1
• 230000007704 transition Effects 0.000 description 1
• 230000014616 translation Effects 0.000 description 1
• 230000016596 traversing start control point of mitotic cell cycle Effects 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• 229910052722 tritium Inorganic materials 0.000 description 1
• 230000004565 tumor cell growth Effects 0.000 description 1
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
• 231100000588 tumorigenic Toxicity 0.000 description 1
• 230000000381 tumorigenic effect Effects 0.000 description 1
• ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
• 229960001055 uracil mustard Drugs 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• 229960003048 vinblastine Drugs 0.000 description 1
• JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound 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 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
• 229960004528 vincristine Drugs 0.000 description 1
• OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
• OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 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
• 229960004355 vindesine Drugs 0.000 description 1
• GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(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 GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
• 229960002066 vinorelbine Drugs 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 229950005839 vinzolidine Drugs 0.000 description 1
• 230000008673 vomiting Effects 0.000 description 1
• 210000002268 wool Anatomy 0.000 description 1
• 150000003751 zinc Chemical class 0.000 description 1