CA2319752A1 - Use of epothilones for the treatment of cancer - Google Patents
Use of epothilones for the treatment of cancer Download PDFInfo
- Publication number
- CA2319752A1 CA2319752A1 CA002319752A CA2319752A CA2319752A1 CA 2319752 A1 CA2319752 A1 CA 2319752A1 CA 002319752 A CA002319752 A CA 002319752A CA 2319752 A CA2319752 A CA 2319752A CA 2319752 A1 CA2319752 A1 CA 2319752A1
- Authority
- CA
- Canada
- Prior art keywords
- treatment
- epothilone
- pharmaceutical preparation
- tumor
- proliferative disease
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 238000011282 treatment Methods 0.000 title claims abstract description 406
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 304
- 229930013356 epothilone Natural products 0.000 title claims abstract description 127
- HESCAJZNRMSMJG-KKQRBIROSA-N epothilone A Chemical class C/C([C@@H]1C[C@@H]2O[C@@H]2CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 HESCAJZNRMSMJG-KKQRBIROSA-N 0.000 title abstract description 56
- 201000011510 cancer Diseases 0.000 title description 42
- HESCAJZNRMSMJG-HGYUPSKWSA-N epothilone A Natural products O=C1[C@H](C)[C@H](O)[C@H](C)CCC[C@H]2O[C@H]2C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C HESCAJZNRMSMJG-HGYUPSKWSA-N 0.000 claims abstract description 239
- QXRSDHAAWVKZLJ-OXZHEXMSSA-N Epothilone B Natural products O=C1[C@H](C)[C@H](O)[C@@H](C)CCC[C@@]2(C)O[C@H]2C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C QXRSDHAAWVKZLJ-OXZHEXMSSA-N 0.000 claims abstract description 199
- QXRSDHAAWVKZLJ-PVYNADRNSA-N epothilone B Chemical compound C/C([C@@H]1C[C@@H]2O[C@]2(C)CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 QXRSDHAAWVKZLJ-PVYNADRNSA-N 0.000 claims abstract description 199
- 201000010099 disease Diseases 0.000 claims abstract description 143
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 143
- 230000002062 proliferating effect Effects 0.000 claims abstract description 125
- 150000003883 epothilone derivatives Chemical class 0.000 claims abstract description 113
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 116
- 229930012538 Paclitaxel Natural products 0.000 claims description 96
- 229960001592 paclitaxel Drugs 0.000 claims description 96
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 96
- 241001465754 Metazoa Species 0.000 claims description 84
- 238000000034 method Methods 0.000 claims description 69
- 238000004519 manufacturing process Methods 0.000 claims description 60
- 230000000259 anti-tumor effect Effects 0.000 claims description 46
- 230000003442 weekly effect Effects 0.000 claims description 46
- 238000001802 infusion Methods 0.000 claims description 39
- 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 claims description 36
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 34
- 229960002949 fluorouracil Drugs 0.000 claims description 34
- 206010027476 Metastases Diseases 0.000 claims description 33
- 230000000973 chemotherapeutic effect Effects 0.000 claims description 33
- 238000001990 intravenous administration Methods 0.000 claims description 29
- 239000002246 antineoplastic agent Substances 0.000 claims description 25
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 22
- 208000026310 Breast neoplasm Diseases 0.000 claims description 21
- 208000037841 lung tumor Diseases 0.000 claims description 19
- 230000009401 metastasis Effects 0.000 claims description 19
- 208000023958 prostate neoplasm Diseases 0.000 claims description 19
- 206010006187 Breast cancer Diseases 0.000 claims description 18
- 239000003937 drug carrier Substances 0.000 claims description 18
- 208000020816 lung neoplasm Diseases 0.000 claims description 17
- 210000002307 prostate Anatomy 0.000 claims description 15
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 10
- 241000282412 Homo Species 0.000 claims description 9
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 9
- 230000036457 multidrug resistance Effects 0.000 claims description 8
- 229940088597 hormone Drugs 0.000 claims description 7
- 239000005556 hormone Substances 0.000 claims description 7
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 6
- 210000004072 lung Anatomy 0.000 claims description 6
- 206010033128 Ovarian cancer Diseases 0.000 claims description 5
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 5
- 238000011255 standard chemotherapy Methods 0.000 claims description 5
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 5
- 206010005003 Bladder cancer Diseases 0.000 claims description 4
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 4
- 206010029260 Neuroblastoma Diseases 0.000 claims description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 4
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 4
- 210000000481 breast Anatomy 0.000 claims description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 4
- 201000001441 melanoma Diseases 0.000 claims description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 4
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 4
- 206010038389 Renal cancer Diseases 0.000 claims description 3
- 206010017758 gastric cancer Diseases 0.000 claims description 3
- 201000010982 kidney cancer Diseases 0.000 claims description 3
- 201000011549 stomach cancer Diseases 0.000 claims description 3
- 230000001225 therapeutic effect Effects 0.000 claims description 3
- 208000026037 malignant tumor of neck Diseases 0.000 claims description 2
- 208000025440 neoplasm of neck Diseases 0.000 claims 6
- 238000011269 treatment regimen Methods 0.000 abstract description 5
- 210000004027 cell Anatomy 0.000 description 91
- 239000000306 component Substances 0.000 description 76
- 230000037396 body weight Effects 0.000 description 47
- 230000004044 response Effects 0.000 description 42
- 241000699670 Mus sp. Species 0.000 description 32
- 230000000694 effects Effects 0.000 description 31
- 239000000203 mixture Substances 0.000 description 31
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
- 150000001875 compounds Chemical class 0.000 description 24
- 239000003814 drug Substances 0.000 description 23
- 229940079593 drug Drugs 0.000 description 23
- 235000002639 sodium chloride Nutrition 0.000 description 23
- 230000001988 toxicity Effects 0.000 description 23
- 231100000419 toxicity Toxicity 0.000 description 23
- 238000002474 experimental method Methods 0.000 description 22
- 238000009472 formulation Methods 0.000 description 21
- 239000003795 chemical substances by application Substances 0.000 description 19
- 231100000371 dose-limiting toxicity Toxicity 0.000 description 19
- 229940026778 other chemotherapeutics in atc Drugs 0.000 description 18
- 238000011084 recovery Methods 0.000 description 18
- 150000003839 salts Chemical class 0.000 description 18
- 239000003981 vehicle Substances 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 206010060862 Prostate cancer Diseases 0.000 description 15
- 229940127089 cytotoxic agent Drugs 0.000 description 15
- 239000003978 infusion fluid Substances 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 14
- 238000009121 systemic therapy Methods 0.000 description 14
- 108091022875 Microtubule Proteins 0.000 description 13
- 102000029749 Microtubule Human genes 0.000 description 13
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 13
- 210000004688 microtubule Anatomy 0.000 description 13
- 238000011580 nude mouse model Methods 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 206010061818 Disease progression Diseases 0.000 description 12
- -1 TAXOL~ Chemical class 0.000 description 12
- 208000029742 colonic neoplasm Diseases 0.000 description 12
- 230000005750 disease progression Effects 0.000 description 12
- 238000001727 in vivo Methods 0.000 description 12
- 239000008194 pharmaceutical composition Substances 0.000 description 12
- 239000003381 stabilizer Substances 0.000 description 12
- 230000004083 survival effect Effects 0.000 description 12
- 230000004614 tumor growth Effects 0.000 description 12
- 230000001028 anti-proliverative effect Effects 0.000 description 11
- 239000000463 material Substances 0.000 description 11
- 238000011272 standard treatment Methods 0.000 description 11
- 206010009944 Colon cancer Diseases 0.000 description 10
- 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 10
- 208000037844 advanced solid tumor Diseases 0.000 description 10
- 239000002254 cytotoxic agent Substances 0.000 description 10
- 231100000599 cytotoxic agent Toxicity 0.000 description 10
- 230000003285 pharmacodynamic effect Effects 0.000 description 10
- 230000035755 proliferation Effects 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 238000007619 statistical method Methods 0.000 description 10
- 238000007920 subcutaneous administration Methods 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 239000004480 active ingredient Substances 0.000 description 9
- 239000012736 aqueous medium Substances 0.000 description 9
- 238000002512 chemotherapy Methods 0.000 description 9
- 239000007951 isotonicity adjuster Substances 0.000 description 9
- 230000036961 partial effect Effects 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 231100000402 unacceptable toxicity Toxicity 0.000 description 9
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 8
- 206010003694 Atrophy Diseases 0.000 description 8
- 238000011729 BALB/c nude mouse Methods 0.000 description 8
- 241000699660 Mus musculus Species 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 239000003963 antioxidant agent Substances 0.000 description 8
- 235000006708 antioxidants Nutrition 0.000 description 8
- 230000037444 atrophy Effects 0.000 description 8
- 239000012153 distilled water Substances 0.000 description 8
- 238000011156 evaluation Methods 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 210000000056 organ Anatomy 0.000 description 8
- 239000004033 plastic Substances 0.000 description 8
- 229920003023 plastic Polymers 0.000 description 8
- 210000002966 serum Anatomy 0.000 description 8
- 201000009030 Carcinoma Diseases 0.000 description 7
- 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 7
- 210000001185 bone marrow Anatomy 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 230000008859 change Effects 0.000 description 7
- 229960001031 glucose Drugs 0.000 description 7
- 210000000952 spleen Anatomy 0.000 description 7
- 238000001061 Dunnett's test Methods 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 230000002411 adverse Effects 0.000 description 6
- 230000002280 anti-androgenic effect Effects 0.000 description 6
- 239000000051 antiandrogen Substances 0.000 description 6
- 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 6
- 238000001574 biopsy Methods 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 6
- 231100000026 common toxicity Toxicity 0.000 description 6
- 239000012141 concentrate Substances 0.000 description 6
- 230000034994 death Effects 0.000 description 6
- 231100000517 death Toxicity 0.000 description 6
- 230000003292 diminished effect Effects 0.000 description 6
- 239000011521 glass Substances 0.000 description 6
- 239000008103 glucose Substances 0.000 description 6
- 230000012010 growth Effects 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 210000001165 lymph node Anatomy 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 238000006722 reduction reaction Methods 0.000 description 6
- 210000001541 thymus gland Anatomy 0.000 description 6
- 238000002054 transplantation Methods 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- 238000000729 Fisher's exact test Methods 0.000 description 5
- 238000000692 Student's t-test Methods 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 210000000349 chromosome Anatomy 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 230000002496 gastric effect Effects 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- 230000002489 hematologic effect Effects 0.000 description 5
- 206010061289 metastatic neoplasm Diseases 0.000 description 5
- 210000000440 neutrophil Anatomy 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 4
- 238000011725 BALB/c mouse Methods 0.000 description 4
- 241000282472 Canis lupus familiaris Species 0.000 description 4
- 208000002699 Digestive System Neoplasms Diseases 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- 206010016654 Fibrosis Diseases 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- 241000725303 Human immunodeficiency virus Species 0.000 description 4
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 4
- 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 4
- 208000015634 Rectal Neoplasms Diseases 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 229940123237 Taxane Drugs 0.000 description 4
- 210000001015 abdomen Anatomy 0.000 description 4
- 230000005856 abnormality Effects 0.000 description 4
- 230000001154 acute effect Effects 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 229940100198 alkylating agent Drugs 0.000 description 4
- 239000002168 alkylating agent Substances 0.000 description 4
- 210000001772 blood platelet Anatomy 0.000 description 4
- 210000000988 bone and bone Anatomy 0.000 description 4
- 210000000038 chest Anatomy 0.000 description 4
- 210000001072 colon Anatomy 0.000 description 4
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 230000008034 disappearance Effects 0.000 description 4
- 229940011871 estrogen Drugs 0.000 description 4
- 239000000262 estrogen Substances 0.000 description 4
- 230000007717 exclusion Effects 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 229940014259 gelatin Drugs 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 4
- 201000010536 head and neck cancer Diseases 0.000 description 4
- 238000002513 implantation Methods 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 230000003204 osmotic effect Effects 0.000 description 4
- 238000007427 paired t-test Methods 0.000 description 4
- 210000004197 pelvis Anatomy 0.000 description 4
- 239000008389 polyethoxylated castor oil Substances 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
- 201000001514 prostate carcinoma Diseases 0.000 description 4
- 238000001959 radiotherapy Methods 0.000 description 4
- 230000000306 recurrent effect Effects 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 229960002668 sodium chloride Drugs 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000001356 surgical procedure Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- 239000000439 tumor marker Substances 0.000 description 4
- 235000019786 weight gain Nutrition 0.000 description 4
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000003098 androgen Substances 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 230000001093 anti-cancer Effects 0.000 description 3
- 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 3
- 230000003078 antioxidant effect Effects 0.000 description 3
- 210000001124 body fluid Anatomy 0.000 description 3
- 239000010839 body fluid Substances 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 239000012876 carrier material Substances 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 230000001186 cumulative effect Effects 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 239000008298 dragée Substances 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 238000011221 initial treatment Methods 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 231100000682 maximum tolerated dose Toxicity 0.000 description 3
- 230000010534 mechanism of action Effects 0.000 description 3
- 230000001394 metastastic effect Effects 0.000 description 3
- 229960001156 mitoxantrone Drugs 0.000 description 3
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- WQEPLUUGTLDZJY-UHFFFAOYSA-N pentadecanoic acid Chemical compound CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 229940068886 polyethylene glycol 300 Drugs 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 210000000664 rectum Anatomy 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 231100000041 toxicology testing Toxicity 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- 108010082126 Alanine transaminase Proteins 0.000 description 2
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000031648 Body Weight Changes Diseases 0.000 description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 description 2
- 206010061809 Cervix carcinoma stage 0 Diseases 0.000 description 2
- 206010008909 Chronic Hepatitis Diseases 0.000 description 2
- 206010052360 Colorectal adenocarcinoma Diseases 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 102000054300 EC 2.7.11.- Human genes 0.000 description 2
- 108700035490 EC 2.7.11.- Proteins 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 2
- 108010024636 Glutathione Proteins 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- 206010019755 Hepatitis chronic active Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- 238000001282 Kruskal–Wallis one-way analysis of variance Methods 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- 229930182816 L-glutamine Natural products 0.000 description 2
- 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 2
- 102000008072 Lymphokines Human genes 0.000 description 2
- 108010074338 Lymphokines Proteins 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 2
- 238000011887 Necropsy Methods 0.000 description 2
- 206010028851 Necrosis Diseases 0.000 description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229920002556 Polyethylene Glycol 300 Polymers 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- 208000000453 Skin Neoplasms Diseases 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 238000003639 Student–Newman–Keuls (SNK) method Methods 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 238000008050 Total Bilirubin Reagent Methods 0.000 description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 229940009456 adriamycin Drugs 0.000 description 2
- 229930013930 alkaloid Natural products 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 229940046836 anti-estrogen Drugs 0.000 description 2
- 230000001833 anti-estrogenic effect Effects 0.000 description 2
- 230000000340 anti-metabolite Effects 0.000 description 2
- 230000001946 anti-microtubular Effects 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 229940100197 antimetabolite Drugs 0.000 description 2
- 239000002256 antimetabolite Substances 0.000 description 2
- 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 2
- 239000000074 antisense oligonucleotide Substances 0.000 description 2
- 238000012230 antisense oligonucleotides Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 210000003651 basophil Anatomy 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
- 229940092714 benzenesulfonic acid Drugs 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000003181 biological factor Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000004579 body weight change Effects 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000004359 castor oil Substances 0.000 description 2
- 235000019438 castor oil Nutrition 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 208000020832 chronic kidney disease Diseases 0.000 description 2
- 230000007882 cirrhosis Effects 0.000 description 2
- 208000019425 cirrhosis of liver Diseases 0.000 description 2
- 229960001338 colchicine Drugs 0.000 description 2
- 229940109239 creatinine Drugs 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 230000001934 delay Effects 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- UKMSUNONTOPOIO-UHFFFAOYSA-N docosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCC(O)=O UKMSUNONTOPOIO-UHFFFAOYSA-N 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 229960004679 doxorubicin Drugs 0.000 description 2
- 229940000406 drug candidate Drugs 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- ZQPPMHVWECSIRJ-MDZDMXLPSA-N elaidic acid Chemical compound CCCCCCCC\C=C\CCCCCCCC(O)=O ZQPPMHVWECSIRJ-MDZDMXLPSA-N 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000000925 erythroid effect Effects 0.000 description 2
- 239000000328 estrogen antagonist Substances 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 230000004761 fibrosis Effects 0.000 description 2
- 229960003180 glutathione Drugs 0.000 description 2
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 2
- 230000003394 haemopoietic effect Effects 0.000 description 2
- 230000011132 hemopoiesis Effects 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- KEMQGTRYUADPNZ-UHFFFAOYSA-N heptadecanoic acid Chemical compound CCCCCCCCCCCCCCCCC(O)=O KEMQGTRYUADPNZ-UHFFFAOYSA-N 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 229940125697 hormonal agent Drugs 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 206010020718 hyperplasia Diseases 0.000 description 2
- VKOBVWXKNCXXDE-UHFFFAOYSA-N icosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCC(O)=O VKOBVWXKNCXXDE-UHFFFAOYSA-N 0.000 description 2
- 239000000367 immunologic factor Substances 0.000 description 2
- 230000005917 in vivo anti-tumor Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 229940047124 interferons Drugs 0.000 description 2
- 210000004347 intestinal mucosa Anatomy 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 210000005240 left ventricle Anatomy 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 231100000225 lethality Toxicity 0.000 description 2
- HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 description 2
- 229960003881 letrozole Drugs 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 210000002751 lymph Anatomy 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229960004857 mitomycin Drugs 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 208000023983 oral cavity neoplasm Diseases 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 229920001451 polypropylene glycol Polymers 0.000 description 2
- 238000009258 post-therapy Methods 0.000 description 2
- 238000009597 pregnancy test Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 230000001850 reproductive effect Effects 0.000 description 2
- 230000008261 resistance mechanism Effects 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 201000000849 skin cancer Diseases 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000008354 sodium chloride injection Substances 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 206010041823 squamous cell carcinoma Diseases 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 229940063683 taxotere Drugs 0.000 description 2
- 231100000816 toxic dose Toxicity 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical class [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- SZHOJFHSIKHZHA-UHFFFAOYSA-N tridecanoic acid Chemical compound CCCCCCCCCCCCC(O)=O SZHOJFHSIKHZHA-UHFFFAOYSA-N 0.000 description 2
- 210000004291 uterus Anatomy 0.000 description 2
- 230000004584 weight gain Effects 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- HONKEGXLWUDTCF-YFKPBYRVSA-N (2s)-2-amino-2-methyl-4-phosphonobutanoic acid Chemical compound OC(=O)[C@](N)(C)CCP(O)(O)=O HONKEGXLWUDTCF-YFKPBYRVSA-N 0.000 description 1
- OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- 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
- GZCWLCBFPRFLKL-UHFFFAOYSA-N 1-prop-2-ynoxypropan-2-ol Chemical compound CC(O)COCC#C GZCWLCBFPRFLKL-UHFFFAOYSA-N 0.000 description 1
- OIQOAYVCKAHSEJ-UHFFFAOYSA-N 2-[2,3-bis(2-hydroxyethoxy)propoxy]ethanol;hexadecanoic acid;octadecanoic acid Chemical compound OCCOCC(OCCO)COCCO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O OIQOAYVCKAHSEJ-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
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 102000013563 Acid Phosphatase Human genes 0.000 description 1
- 108010051457 Acid Phosphatase Proteins 0.000 description 1
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 235000021357 Behenic acid Nutrition 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- DPUOLQHDNGRHBS-UHFFFAOYSA-N Brassidinsaeure Natural products CCCCCCCCC=CCCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-UHFFFAOYSA-N 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- RZZPDXZPRHQOCG-OJAKKHQRSA-O CDP-choline(1+) Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OCC[N+](C)(C)C)O[C@H]1N1C(=O)N=C(N)C=C1 RZZPDXZPRHQOCG-OJAKKHQRSA-O 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 229920002307 Dextran Polymers 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
- 206010059866 Drug resistance Diseases 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- URXZXNYJPAJJOQ-UHFFFAOYSA-N Erucic acid Natural products CCCCCCC=CCCCCCCCCCCCC(O)=O URXZXNYJPAJJOQ-UHFFFAOYSA-N 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
- 208000002633 Febrile Neutropenia Diseases 0.000 description 1
- 231100001273 GLP toxicology study Toxicity 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 208000031856 Haemosiderosis Diseases 0.000 description 1
- 101000616438 Homo sapiens Microtubule-associated protein 4 Proteins 0.000 description 1
- 206010062904 Hormone-refractory prostate cancer Diseases 0.000 description 1
- 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 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 208000007433 Lymphatic Metastasis Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 206010027457 Metastases to liver Diseases 0.000 description 1
- 206010027459 Metastases to lymph nodes Diseases 0.000 description 1
- 102100021794 Microtubule-associated protein 4 Human genes 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-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
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 208000036366 Sensation of pressure Diseases 0.000 description 1
- 241000862997 Sorangium cellulosum Species 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical group OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 208000026487 Triploidy Diseases 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- 102000004243 Tubulin Human genes 0.000 description 1
- 108090000704 Tubulin Proteins 0.000 description 1
- 208000008385 Urogenital Neoplasms Diseases 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 210000002593 Y chromosome Anatomy 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
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 102000001307 androgen receptors Human genes 0.000 description 1
- 108010080146 androgen receptors Proteins 0.000 description 1
- 229940030486 androgens Drugs 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 229940027983 antiseptic and disinfectant quaternary ammonium compound Drugs 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 210000003567 ascitic fluid Anatomy 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229940116226 behenic acid Drugs 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000005388 borosilicate glass Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 235000011010 calcium phosphates Nutrition 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
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 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
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000012829 chemotherapy agent Substances 0.000 description 1
- 229960001284 citicoline Drugs 0.000 description 1
- HNEGQIOMVPPMNR-IHWYPQMZSA-N citraconic acid Chemical compound OC(=O)C(/C)=C\C(O)=O HNEGQIOMVPPMNR-IHWYPQMZSA-N 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229940000425 combination drug Drugs 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 235000013681 dietary sucrose Nutrition 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- DPUOLQHDNGRHBS-KTKRTIGZSA-N erucic acid Chemical compound CCCCCCCC\C=C/CCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-KTKRTIGZSA-N 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 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
- LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical compound CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 238000009093 first-line therapy Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 238000012252 genetic analysis Methods 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 229960003711 glyceryl trinitrate Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 238000013415 human tumor xenograft model Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 230000003463 hyperproliferative effect Effects 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 206010073095 invasive ductal breast carcinoma Diseases 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229940074928 isopropyl myristate Drugs 0.000 description 1
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
- 229940075495 isopropyl palmitate Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000002429 large intestine 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
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 201000005249 lung adenocarcinoma Diseases 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229940057948 magnesium stearate Drugs 0.000 description 1
- 229940091250 magnesium supplement Drugs 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 101150014751 map4 gene Proteins 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 230000031864 metaphase Effects 0.000 description 1
- 208000010658 metastatic prostate carcinoma Diseases 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960002900 methylcellulose Drugs 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 description 1
- 229960000907 methylthioninium chloride Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000011369 optimal treatment Methods 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 238000010525 oxidative degradation reaction Methods 0.000 description 1
- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000002974 pharmacogenomic effect Effects 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 150000004713 phosphodiesters Chemical class 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 230000005195 poor health Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940116317 potato starch Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 201000005825 prostate adenocarcinoma Diseases 0.000 description 1
- 210000005267 prostate cell Anatomy 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 201000002793 renal fibrosis Diseases 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 210000001995 reticulocyte Anatomy 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229940100486 rice starch Drugs 0.000 description 1
- 235000003441 saturated fatty acids Nutrition 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 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
- 230000002226 simultaneous effect Effects 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000005361 soda-lime glass Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000011885 synergistic combination Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000002456 taxol group Chemical group 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical class CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
- 229920001169 thermoplastic Polymers 0.000 description 1
- 230000002992 thymic effect Effects 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 238000002562 urinalysis Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9803905.0 | 1998-02-25 | ||
| GB9803907.6 | 1998-02-25 | ||
| GBGB9803905.0A GB9803905D0 (en) | 1998-02-25 | 1998-02-25 | Organic compounds |
| GBGB9803907.6A GB9803907D0 (en) | 1998-02-25 | 1998-02-25 | Organic compounds |
| GBGB9805936.3A GB9805936D0 (en) | 1998-03-19 | 1998-03-19 | Organic compounds |
| GB9805937.1 | 1998-03-19 | ||
| GBGB9805937.1A GB9805937D0 (en) | 1998-03-19 | 1998-03-19 | Organic compounds |
| GB9805936.3 | 1998-03-19 | ||
| US09/233,993 US6302838B1 (en) | 1998-02-25 | 1999-01-19 | Cancer treatment with epothilones |
| US09/233,993 | 1999-01-19 | ||
| PCT/EP1999/001147 WO1999043320A1 (en) | 1998-02-25 | 1999-02-23 | Use of epothilones for the treatment of cancer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2319752A1 true CA2319752A1 (en) | 1999-09-02 |
Family
ID=27517450
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002319752A Withdrawn CA2319752A1 (en) | 1998-02-25 | 1999-02-23 | Use of epothilones for the treatment of cancer |
Country Status (10)
| Country | Link |
|---|---|
| US (4) | US6635666B2 (enExample) |
| EP (1) | EP1056453B1 (enExample) |
| JP (1) | JP2002504511A (enExample) |
| AU (1) | AU755944B2 (enExample) |
| BE (1) | BE1011980A5 (enExample) |
| CA (1) | CA2319752A1 (enExample) |
| FR (1) | FR2775187B1 (enExample) |
| IT (1) | ITMI990375A1 (enExample) |
| NZ (1) | NZ506187A (enExample) |
| WO (1) | WO1999043320A1 (enExample) |
Families Citing this family (68)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1440973A3 (de) | 1995-11-17 | 2004-10-20 | Gesellschaft für biotechnologische Forschung mbH (GBF) | Epothilonderivate, Herstellung und Mittel |
| PL193229B1 (pl) | 1996-11-18 | 2007-01-31 | F Biotechnologische Forschung | Epotylon C, epotylon D, epotylon E i epotylon F, sposób biotransformacji epotylonu A, sposób biotransformacji epotylonu B oraz środek leczniczy |
| US6867305B2 (en) | 1996-12-03 | 2005-03-15 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| EP0977563B1 (en) | 1996-12-03 | 2005-10-12 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto, analogues and uses thereof |
| US6204388B1 (en) * | 1996-12-03 | 2001-03-20 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| US6605599B1 (en) | 1997-07-08 | 2003-08-12 | Bristol-Myers Squibb Company | Epothilone derivatives |
| US6365749B1 (en) | 1997-12-04 | 2002-04-02 | Bristol-Myers Squibb Company | Process for the preparation of ring-opened epothilone intermediates which are useful for the preparation of epothilone analogs |
| FR2775187B1 (fr) * | 1998-02-25 | 2003-02-21 | Novartis Ag | Utilisation de l'epothilone b pour la fabrication d'une preparation pharmaceutique antiproliferative et d'une composition comprenant l'epothilone b comme agent antiproliferatif in vivo |
| US6380395B1 (en) | 1998-04-21 | 2002-04-30 | Bristol-Myers Squibb Company | 12, 13-cyclopropane epothilone derivatives |
| US6498257B1 (en) | 1998-04-21 | 2002-12-24 | Bristol-Myers Squibb Company | 2,3-olefinic epothilone derivatives |
| US6410301B1 (en) | 1998-11-20 | 2002-06-25 | Kosan Biosciences, Inc. | Myxococcus host cells for the production of epothilones |
| EP1135470A2 (en) | 1998-11-20 | 2001-09-26 | Kosan Biosciences, Inc. | Recombinant methods and materials for producing epothilone and epothilone derivatives |
| US20020058286A1 (en) * | 1999-02-24 | 2002-05-16 | Danishefsky Samuel J. | Synthesis of epothilones, intermediates thereto and analogues thereof |
| EP1154779A2 (en) * | 1999-02-26 | 2001-11-21 | Napro Biotherapeutics, Inc. | Treatment regimen for prostate cancer, initiated after androgen ablative therapy has started |
| AU3606700A (en) * | 1999-02-26 | 2000-09-14 | Napro Biotherapeutics, Inc. | Treatment regimen for hormone-sensitive cancers |
| US20050042275A1 (en) * | 1999-08-04 | 2005-02-24 | Jean-Claude Sonntag | Epothilone compositions |
| US6414015B1 (en) | 2000-01-28 | 2002-07-02 | Utah State University | Laulimalide microtubule stabilizing agents |
| US6518421B1 (en) * | 2000-03-20 | 2003-02-11 | Bristol-Myers Squibb Company | Process for the preparation of epothilone analogs |
| US6593115B2 (en) | 2000-03-24 | 2003-07-15 | Bristol-Myers Squibb Co. | Preparation of epothilone intermediates |
| UA75365C2 (en) * | 2000-08-16 | 2006-04-17 | Bristol Myers Squibb Co | Epothilone analog polymorph modifications, a method for obtaining thereof (variants), a pharmaceutical composition based thereon |
| RU2003126171A (ru) | 2001-01-25 | 2005-02-27 | Бристол-Маерс Сквибб Компани (Us) | Парентеральный состав, содержащий аналоги эпотилона |
| EE05301B1 (et) * | 2001-01-25 | 2010-06-15 | Bristol-Myers Squibb Company | Meetod epotilooni analooge sisaldavate ravimvormide valmistamiseks ning nende kasutamine ravimi valmistamiseks |
| IL156578A0 (en) * | 2001-01-25 | 2004-01-04 | Bristol Myers Squibb Co | A method for formulating an epothilone analog for pharmaceutical use and pharmaceutical preparations including an epothilone analog |
| NZ526871A (en) * | 2001-01-25 | 2006-01-27 | Bristol Myers Squibb Co | Pharmaceutical dosage forms of epothilones for oral administration |
| EP1368030A1 (en) | 2001-02-20 | 2003-12-10 | Bristol-Myers Squibb Company | Epothilone derivatives for the treatment of refractory tumors |
| EE200300396A (et) | 2001-02-20 | 2003-12-15 | Bristol-Myers Squibb Company | Epotilooni derivaatide kasutamine refraktaarsete kasvajate raviks |
| WO2002072085A1 (en) | 2001-03-14 | 2002-09-19 | Bristol-Myers Squibb Company | Combination of epothilone analogs and chemotherapeutic agents for the treatment of proliferative diseases |
| DE60229922D1 (de) * | 2001-03-19 | 2009-01-02 | Novartis Ag | Kombinationen, ein antidiarrhoikum und epothilon oder ein epothilonderivat enthaltend |
| WO2002098868A1 (en) | 2001-06-01 | 2002-12-12 | Bristol-Myers Squibb Company | Epothilone derivatives |
| TWI315982B (en) * | 2001-07-19 | 2009-10-21 | Novartis Ag | Combinations comprising epothilones and pharmaceutical uses thereof |
| AU2008203233B2 (en) * | 2001-07-19 | 2010-04-29 | Novartis Ag | Combinations comprising epothilones and pharmaceutical uses thereof |
| TW200408407A (en) * | 2001-11-30 | 2004-06-01 | Dana Farber Cancer Inst Inc | Methods and compositions for modulating the immune system and uses thereof |
| TWI287986B (en) * | 2001-12-13 | 2007-10-11 | Novartis Ag | Use of Epothilones for the treatment of the carcinoid syndrome |
| JP5384777B2 (ja) * | 2001-12-18 | 2014-01-08 | 有限会社大長企画 | 強筋肉剤、抗炎症剤 |
| NZ533940A (en) * | 2002-01-14 | 2007-06-29 | Novartis Ag | Combinations comprising epothilones and anti-metabolites |
| EP1340498A1 (en) * | 2002-03-01 | 2003-09-03 | Schering Aktiengesellschaft | Use of epothilones in the treatment of brain diseases associated with proliferative processes |
| US7211593B2 (en) | 2002-03-12 | 2007-05-01 | Bristol-Myers Squibb Co. | C12-cyano epothilone derivatives |
| TW200403994A (en) | 2002-04-04 | 2004-03-16 | Bristol Myers Squibb Co | Oral administration of EPOTHILONES |
| DE10217254A1 (de) * | 2002-04-15 | 2003-10-23 | Proteosys Ag | Verwendung von Substanzen zur Behandlung von Tumoren |
| TW200400191A (en) | 2002-05-15 | 2004-01-01 | Bristol Myers Squibb Co | Pharmaceutical compositions and methods of using C-21 modified epothilone derivatives |
| AU2003243561A1 (en) | 2002-06-14 | 2003-12-31 | Bristol-Myers Squibb Company | Combination of epothilone analogs and chemotherapeutic agents for the treatment of proliferative diseases |
| US7649006B2 (en) | 2002-08-23 | 2010-01-19 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| US6921769B2 (en) | 2002-08-23 | 2005-07-26 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| WO2004018478A2 (en) * | 2002-08-23 | 2004-03-04 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto, analogues and uses thereof |
| RS20050235A (sr) | 2002-09-23 | 2007-06-04 | Bristol Myers Squibb Company, | Postupci za pripremanje,izolaciju i prečišćavanje epotilona b i kristalne strukture epotilona b dobijene primenom x-zraka |
| CN100553634C (zh) * | 2002-10-11 | 2009-10-28 | 达纳-法伯癌症研究公司 | 用于治疗多发性骨髓瘤的埃坡霉素衍生物 |
| EP1572193A1 (en) * | 2002-12-09 | 2005-09-14 | Novartis AG | Microtubule stabilisers for treating stenosis in stents |
| US20040146632A1 (en) * | 2003-01-23 | 2004-07-29 | Cristina Sayman | Effective multi-component penetrating and flavoring marinade |
| BRPI0412000A (pt) * | 2003-06-27 | 2006-08-15 | Novartis Ag | tratamento de cáncer com epotilonas |
| MXPA06002393A (es) * | 2003-09-02 | 2006-06-20 | Novartis Ag | Tratamiento de cancer con epotilomas. |
| GB0405898D0 (en) | 2004-03-16 | 2004-04-21 | Novartis Ag | Organic compounds |
| EP1640004A1 (en) * | 2004-09-24 | 2006-03-29 | Schering Aktiengesellschaft | Use of epothilones in the treatment of bone metastases and bone tumors or cancers |
| EP1824458A1 (en) * | 2004-11-18 | 2007-08-29 | Bristol-Myers Squibb Company | Enteric coated bead comprising epothilone or an epothilone analog, and preparation and administration thereof |
| BRPI0518286A2 (pt) * | 2004-11-18 | 2008-11-11 | Bristol Myers Squibb Co | microesfera com revestimento entÉrico contendo ixabepilona e sua preparaÇço |
| US20060121511A1 (en) | 2004-11-30 | 2006-06-08 | Hyerim Lee | Biomarkers and methods for determining sensitivity to microtubule-stabilizing agents |
| JO2596B1 (en) * | 2004-11-30 | 2011-02-27 | نوفارتيس ايه جي | Compositions include epothelones and tyrosine protein kinase inhibitors and their pharmaceutical uses |
| DE102005008309A1 (de) * | 2005-02-17 | 2006-08-24 | Schering Ag | Pharmazeutische Mittel enthaltend fluoralkylhaltige Metallkomplexe und Epothilone |
| KR20090005310A (ko) * | 2006-04-05 | 2009-01-13 | 노파르티스 아게 | 암을 치료하기 위한 치료제의 조합물 |
| JP2010510236A (ja) * | 2006-11-15 | 2010-04-02 | ダナ−ファーバー キャンサー インスティテュート インク． | 安定化させたｍａｍｌペプチドおよびその使用法 |
| EP2170473A1 (en) | 2007-06-20 | 2010-04-07 | Saluc Technologie S.A. | Convertible dining / billiard table |
| EP2065054A1 (en) | 2007-11-29 | 2009-06-03 | Bayer Schering Pharma Aktiengesellschaft | Combinations comprising a prostaglandin and uses thereof |
| DE102007059752A1 (de) | 2007-12-10 | 2009-06-18 | Bayer Schering Pharma Aktiengesellschaft | Funktionalisierte, feste Polymernanopartikel enthaltend Epothilone |
| EP2070521A1 (en) | 2007-12-10 | 2009-06-17 | Bayer Schering Pharma Aktiengesellschaft | Surface-modified nanoparticles |
| JP2012515172A (ja) | 2009-01-14 | 2012-07-05 | エルロン・セラピューティクス・インコーポレイテッド | ペプチド模倣大環状分子 |
| EP2210584A1 (en) | 2009-01-27 | 2010-07-28 | Bayer Schering Pharma Aktiengesellschaft | Stable polymeric composition comprising an epothilone and an amphiphilic block copolymer |
| WO2014116594A1 (en) * | 2013-01-23 | 2014-07-31 | The University Of Toledo | Highly selective anti-cancer agents targeting non-small cell lung cancer and other forms of cancer |
| WO2017004548A1 (en) | 2015-07-01 | 2017-01-05 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| US20210268072A1 (en) * | 2016-06-28 | 2021-09-02 | Alma Mater Studiorum - Universitá Di Bologna | TATk-CDKL5 Fusion Proteins, Compositions, Formulations, and Use Thereof |
Family Cites Families (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US176429A (en) * | 1876-04-25 | Improvement in nut-locks | ||
| US203876A (en) * | 1878-05-21 | Improvement in piston water-meters | ||
| US127432A (en) * | 1872-06-04 | Improvement in tuckers for sewing-machines | ||
| US34452A (en) * | 1862-02-18 | Improvement in railroad joints or chairs | ||
| US253697A (en) * | 1882-02-14 | John halley and alexandee baee | ||
| US142990A (en) * | 1873-09-23 | Improvement in machines for burnishing the shanks of boots and shoes | ||
| US260098A (en) * | 1882-06-27 | Rolls for longitudinally slitting railroad-rails | ||
| US203938A (en) * | 1878-05-21 | Improvement in wire fences | ||
| US87634A (en) * | 1869-03-09 | Improvement in grain-storehouses | ||
| US220295A (en) * | 1879-10-07 | Improvement in hinges | ||
| DE4138042C2 (de) | 1991-11-19 | 1993-10-14 | Biotechnolog Forschung Gmbh | Epothilone, deren Herstellungsverfahren sowie diese Verbindungen enthaltende Mittel |
| US5716939A (en) * | 1993-07-15 | 1998-02-10 | Pfizer Inc. | Amide derivatives of 16-membered ring antibiotic macrolides |
| EP1440973A3 (de) * | 1995-11-17 | 2004-10-20 | Gesellschaft für biotechnologische Forschung mbH (GBF) | Epothilonderivate, Herstellung und Mittel |
| WO1998008849A1 (de) | 1996-08-30 | 1998-03-05 | Novartis Aktiengesellschaft | Verfahren zur herstellung von epothilonen und zwischenprodukte innerhalb des verfahrens |
| US5969145A (en) * | 1996-08-30 | 1999-10-19 | Novartis Ag | Process for the production of epothilones and intermediate products within the process |
| PL193229B1 (pl) | 1996-11-18 | 2007-01-31 | F Biotechnologische Forschung | Epotylon C, epotylon D, epotylon E i epotylon F, sposób biotransformacji epotylonu A, sposób biotransformacji epotylonu B oraz środek leczniczy |
| US6515016B2 (en) | 1996-12-02 | 2003-02-04 | Angiotech Pharmaceuticals, Inc. | Composition and methods of paclitaxel for treating psoriasis |
| US6204388B1 (en) * | 1996-12-03 | 2001-03-20 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| EP0977563B1 (en) * | 1996-12-03 | 2005-10-12 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto, analogues and uses thereof |
| US6660758B1 (en) * | 1996-12-13 | 2003-12-09 | The Scripps Research Institute | Epothilone analogs |
| US6380394B1 (en) * | 1996-12-13 | 2002-04-30 | The Scripps Research Institute | Epothilone analogs |
| US6441186B1 (en) | 1996-12-13 | 2002-08-27 | The Scripps Research Institute | Epothilone analogs |
| DE19701758A1 (de) | 1997-01-20 | 1998-07-23 | Wessjohann Ludgar A Dr | Epothilone-Synthesebausteine |
| DE19713970B4 (de) | 1997-04-04 | 2006-08-31 | R&D-Biopharmaceuticals Gmbh | Epothilone-Synthesebausteine II - Prenylderivate |
| EP0975622B1 (de) * | 1997-04-18 | 2002-10-09 | Studiengesellschaft Kohle mbH | Selektive olefinmetathese von bi- oder polyfunktionellen substraten in komprimiertem kohlendioxid als reaktionsmedium |
| DE19821954A1 (de) | 1997-05-15 | 1998-11-19 | Biotechnolog Forschung Gmbh | Verfahren zur Herstellung eines Epothilon-Derivats |
| DE19720312A1 (de) * | 1997-05-15 | 1998-11-19 | Hoechst Ag | Zubereitung mit erhöhter in vivo Verträglichkeit |
| DE19726627A1 (de) | 1997-06-17 | 1998-12-24 | Schering Ag | Zwischenprodukte, Verfahren zu ihrer Herstellung und ihre Verwendung zur Herstellung von Epothilon |
| US6605599B1 (en) * | 1997-07-08 | 2003-08-12 | Bristol-Myers Squibb Company | Epothilone derivatives |
| JP2001512723A (ja) | 1997-08-09 | 2001-08-28 | シエーリング アクチエンゲゼルシヤフト | 新規エポチロン誘導体、その製法およびその薬学的使用 |
| HUP0101564A3 (en) * | 1998-02-05 | 2002-06-28 | Novartis Ag | Compositions containing epothilone |
| US6194181B1 (en) * | 1998-02-19 | 2001-02-27 | Novartis Ag | Fermentative preparation process for and crystal forms of cytostatics |
| MXPA00008365A (es) | 1998-02-25 | 2002-11-07 | Sloan Kettering Inst Cancer | Sintesis de epotilonas, intermediarios y analogos de las mismas. |
| FR2775187B1 (fr) * | 1998-02-25 | 2003-02-21 | Novartis Ag | Utilisation de l'epothilone b pour la fabrication d'une preparation pharmaceutique antiproliferative et d'une composition comprenant l'epothilone b comme agent antiproliferatif in vivo |
| US6302838B1 (en) * | 1998-02-25 | 2001-10-16 | Novartis Ag | Cancer treatment with epothilones |
| GB9810659D0 (en) | 1998-05-18 | 1998-07-15 | Ciba Geigy Ag | Organic compounds |
| NZ508326A (en) | 1998-06-18 | 2003-10-31 | Novartis Ag | A polyketide synthase and non ribosomal peptide synthase genes, isolated from a myxobacterium, necessary for synthesis of epothiones A and B |
| US6121029A (en) * | 1998-06-18 | 2000-09-19 | Novartis Ag | Genes for the biosynthesis of epothilones |
| WO1999067253A2 (en) | 1998-06-22 | 1999-12-29 | Novartis Ag | Desmethyl epothilones |
| WO2000000485A1 (de) | 1998-06-30 | 2000-01-06 | Schering Aktiengesellschaft | Epothilon-derivate, verfahren zu deren herstellung, zwischenprodukte und ihre pharmazeutische verwendung |
| DE19848306A1 (de) * | 1998-10-14 | 2000-04-20 | Schering Ag | Verfahren zur Herstellung von Epothilon B und Derivaten sowie Zwischenprodukte für dieses Verfahren |
| EP1135470A2 (en) | 1998-11-20 | 2001-09-26 | Kosan Biosciences, Inc. | Recombinant methods and materials for producing epothilone and epothilone derivatives |
| US6780620B1 (en) * | 1998-12-23 | 2004-08-24 | Bristol-Myers Squibb Company | Microbial transformation method for the preparation of an epothilone |
| CA2404938C (en) | 2000-04-28 | 2011-11-01 | Kosan Biosciences, Inc. | Production of polyketides |
| CA2558600C (en) * | 2004-03-10 | 2013-07-09 | Kureha Corporation | A substituted-trialkyl amine compound with anti-viral activity based on antagonism against a chemokine receptor cxcr4 |
-
1999
- 1999-02-16 FR FR9901903A patent/FR2775187B1/fr not_active Expired - Fee Related
- 1999-02-23 NZ NZ506187A patent/NZ506187A/en not_active IP Right Cessation
- 1999-02-23 EP EP99910257A patent/EP1056453B1/en not_active Expired - Lifetime
- 1999-02-23 CA CA002319752A patent/CA2319752A1/en not_active Withdrawn
- 1999-02-23 JP JP2000533117A patent/JP2002504511A/ja not_active Withdrawn
- 1999-02-23 WO PCT/EP1999/001147 patent/WO1999043320A1/en not_active Ceased
- 1999-02-23 AU AU29279/99A patent/AU755944B2/en not_active Ceased
- 1999-02-24 IT IT99MI000375A patent/ITMI990375A1/it unknown
- 1999-02-25 BE BE9900126A patent/BE1011980A5/fr not_active IP Right Cessation
-
2001
- 2001-08-09 US US09/925,119 patent/US6635666B2/en not_active Expired - Fee Related
-
2003
- 2003-08-01 US US10/633,114 patent/US20040024033A1/en not_active Abandoned
-
2005
- 2005-03-24 US US11/089,269 patent/US7091226B2/en not_active Expired - Fee Related
-
2006
- 2006-04-19 US US11/406,896 patent/US7875601B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US7875601B2 (en) | 2011-01-25 |
| FR2775187B1 (fr) | 2003-02-21 |
| AU755944B2 (en) | 2003-01-02 |
| US20060223867A1 (en) | 2006-10-05 |
| US20020028839A1 (en) | 2002-03-07 |
| FR2775187A1 (fr) | 1999-08-27 |
| BE1011980A5 (fr) | 2000-03-07 |
| US20050165071A1 (en) | 2005-07-28 |
| US7091226B2 (en) | 2006-08-15 |
| NZ506187A (en) | 2003-11-28 |
| US20040024033A1 (en) | 2004-02-05 |
| JP2002504511A (ja) | 2002-02-12 |
| EP1056453A1 (en) | 2000-12-06 |
| EP1056453B1 (en) | 2010-10-06 |
| US6635666B2 (en) | 2003-10-21 |
| ITMI990375A1 (it) | 1999-08-25 |
| WO1999043320A1 (en) | 1999-09-02 |
| AU2927999A (en) | 1999-09-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6635666B2 (en) | Cancer treatment with epothilones | |
| US6302838B1 (en) | Cancer treatment with epothilones | |
| US20090069394A1 (en) | Cancer treatment with epothilones | |
| JP2002504511A5 (enExample) | ||
| WO2010086964A1 (ja) | がん治療のための併用療法 | |
| RU2358730C2 (ru) | Производное эпотилона для лечения гепатомы и других раковых заболеваний | |
| AU2003202508B2 (en) | Use of epothilones for the treatment of cancer | |
| RU2242229C2 (ru) | Применение эпотилонов для лечения рака | |
| EP2117539B1 (en) | A method of administering an antitumor compound | |
| AU2004251444B2 (en) | Cancer treatment with epothilones | |
| CA2482687A1 (en) | Treatment of mesothelioma | |
| ES2354193T3 (es) | Utilización de epotilonas para el tratamiento del cáncer. | |
| KR20070037498A (ko) | 에포틸론 조합물 | |
| US20090239878A1 (en) | Combinations of (a) an atp-competitive inhibitor of c-abl kinase activity with (b) two or more other antineoplastic agents |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| AZWI | Withdrawn application |
Effective date: 20130514 |