TW581763B - Combination and pharmaceutical composition comprising FPT inhibitor for treating proliferative diseases - Google Patents

Info

Publication number

TW581763B

TW581763B TW087121355A TW87121355A TW581763B TW 581763 B TW581763 B TW 581763B TW 087121355 A TW087121355 A TW 087121355A TW 87121355 A TW87121355 A TW 87121355A TW 581763 B TW581763 B TW 581763B

Authority

TW

Taiwan

Prior art keywords

patent application

item

scope

group

alkyl

Prior art date

1997-12-22

Links

• Espacenet
• Global Dossier
• Discuss

• 201000010099 disease Diseases 0.000 title claims abstract description 45
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 45
• 230000002062 proliferating effect Effects 0.000 title claims abstract description 33
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 31
• 239000003112 inhibitor Substances 0.000 title claims description 76
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 75
• 238000001959 radiotherapy Methods 0.000 claims abstract description 11
• 125000000217 alkyl group Chemical group 0.000 claims description 310
• 150000001875 compounds Chemical class 0.000 claims description 266
• -1 Diethyl Estradiol Chemical compound 0.000 claims description 152
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 84
• 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 75
• 229960001592 paclitaxel Drugs 0.000 claims description 73
• 229930012538 Paclitaxel Natural products 0.000 claims description 72
• 239000003795 chemical substances by application Substances 0.000 claims description 61
• 238000011282 treatment Methods 0.000 claims description 57
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 55
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 52
• 230000001028 anti-proliverative effect Effects 0.000 claims description 43
• 229910052739 hydrogen Inorganic materials 0.000 claims description 42
• 229910052757 nitrogen Inorganic materials 0.000 claims description 40
• 239000001257 hydrogen Substances 0.000 claims description 37
• 201000011510 cancer Diseases 0.000 claims description 34
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 33
• 230000005855 radiation Effects 0.000 claims description 30
• 150000001412 amines Chemical class 0.000 claims description 26
• 208000026310 Breast neoplasm Diseases 0.000 claims description 24
• 238000012360 testing method Methods 0.000 claims description 24
• 206010006187 Breast cancer Diseases 0.000 claims description 22
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 22
• MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 claims description 19
• 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 18
• 201000002528 pancreatic cancer Diseases 0.000 claims description 17
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 16
• 239000000460 chlorine Substances 0.000 claims description 16
• 229960002949 fluorouracil Drugs 0.000 claims description 16
• 230000000694 effects Effects 0.000 claims description 15
• 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 claims description 15
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 13
• 208000008443 pancreatic carcinoma Diseases 0.000 claims description 13
• 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 12
• 229960005277 gemcitabine Drugs 0.000 claims description 12
• 201000005202 lung cancer Diseases 0.000 claims description 12
• 208000020816 lung neoplasm Diseases 0.000 claims description 12
• 238000002360 preparation method Methods 0.000 claims description 12
• 108091022875 Microtubule Proteins 0.000 claims description 11
• 102000029749 Microtubule Human genes 0.000 claims description 11
• 210000004688 microtubule Anatomy 0.000 claims description 11
• 229960003604 testosterone Drugs 0.000 claims description 11
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
• BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 claims description 10
• 229910052801 chlorine Inorganic materials 0.000 claims description 10
• 229960004964 temozolomide Drugs 0.000 claims description 10
• 229960004528 vincristine Drugs 0.000 claims description 10
• 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 claims description 10
• 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 claims description 10
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 9
• 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 claims description 9
• 206010060862 Prostate cancer Diseases 0.000 claims description 9
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 9
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 8
• 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 claims description 8
• 125000004429 atom Chemical group 0.000 claims description 8
• 208000029742 colonic neoplasm Diseases 0.000 claims description 8
• 229960004397 cyclophosphamide Drugs 0.000 claims description 8
• 206010009944 Colon cancer Diseases 0.000 claims description 7
• 210000000481 breast Anatomy 0.000 claims description 7
• 206010005003 Bladder cancer Diseases 0.000 claims description 6
• 108010092160 Dactinomycin Proteins 0.000 claims description 6
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 6
• XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 claims description 6
• 229960001220 amsacrine Drugs 0.000 claims description 6
• HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 claims description 6
• 229960004961 mechlorethamine Drugs 0.000 claims description 6
• 201000005112 urinary bladder cancer Diseases 0.000 claims description 6
• 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 claims description 5
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims description 5
• 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 claims description 5
• 206010058314 Dysplasia Diseases 0.000 claims description 5
• 208000032612 Glial tumor Diseases 0.000 claims description 5
• 206010018338 Glioma Diseases 0.000 claims description 5
• BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 claims description 5
• 108010069236 Goserelin Proteins 0.000 claims description 5
• 102000014150 Interferons Human genes 0.000 claims description 5
• 108010050904 Interferons Proteins 0.000 claims description 5
• HLFSDGLLUJUHTE-SNVBAGLBSA-N Levamisole Chemical compound C1([C@H]2CN3CCSC3=N2)=CC=CC=C1 HLFSDGLLUJUHTE-SNVBAGLBSA-N 0.000 claims description 5
• GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 claims description 5
• ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 claims description 5
• 229960000473 altretamine Drugs 0.000 claims description 5
• ROBVIMPUHSLWNV-UHFFFAOYSA-N aminoglutethimide Chemical compound C=1C=C(N)C=CC=1C1(CC)CCC(=O)NC1=O ROBVIMPUHSLWNV-UHFFFAOYSA-N 0.000 claims description 5
• 229960003437 aminoglutethimide Drugs 0.000 claims description 5
• 229960002092 busulfan Drugs 0.000 claims description 5
• 229960004562 carboplatin Drugs 0.000 claims description 5
• 229960000684 cytarabine Drugs 0.000 claims description 5
• FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 claims description 5
• 229960001842 estramustine Drugs 0.000 claims description 5
• 229960000961 floxuridine Drugs 0.000 claims description 5
• 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 claims description 5
• UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 claims description 5
• 229940079322 interferon Drugs 0.000 claims description 5
• 229960001614 levamisole Drugs 0.000 claims description 5
• 229960002247 lomustine Drugs 0.000 claims description 5
• 201000001441 melanoma Diseases 0.000 claims description 5
• SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 claims description 5
• 229960001924 melphalan Drugs 0.000 claims description 5
• 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 claims description 5
• 229960001156 mitoxantrone Drugs 0.000 claims description 5
• 208000025113 myeloid leukemia Diseases 0.000 claims description 5
• XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 claims description 5
• 229960004618 prednisone Drugs 0.000 claims description 5
• 229960001052 streptozocin Drugs 0.000 claims description 5
• 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 claims description 5
• 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 claims description 5
• 229960005026 toremifene Drugs 0.000 claims description 5
• 238000012546 transfer Methods 0.000 claims description 5
• 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 claims description 5
• 229960004355 vindesine Drugs 0.000 claims description 5
• 229960001230 asparagine Drugs 0.000 claims description 4
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 4
• 229960004316 cisplatin Drugs 0.000 claims description 4
• HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 claims description 4
• 229960001101 ifosfamide Drugs 0.000 claims description 4
• PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 claims description 4
• 229960002985 medroxyprogesterone acetate Drugs 0.000 claims description 4
• 210000000496 pancreas Anatomy 0.000 claims description 4
• 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 claims description 4
• 239000002689 soil Substances 0.000 claims description 4
• 208000011580 syndromic disease Diseases 0.000 claims description 4
• 229960001603 tamoxifen Drugs 0.000 claims description 4
• 150000004579 taxol derivatives Chemical class 0.000 claims description 4
• FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 claims description 3
• IDPUKCWIGUEADI-UHFFFAOYSA-N 5-[bis(2-chloroethyl)amino]uracil Chemical compound ClCCN(CCCl)C1=CNC(=O)NC1=O IDPUKCWIGUEADI-UHFFFAOYSA-N 0.000 claims description 3
• 108700023418 Amidases Proteins 0.000 claims description 3
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 3
• KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims description 3
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 3
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 3
• 102000005922 amidase Human genes 0.000 claims description 3
• 230000008859 change Effects 0.000 claims description 3
• 229960003901 dacarbazine Drugs 0.000 claims description 3
• 229960000485 methotrexate Drugs 0.000 claims description 3
• 229910052702 rhenium Inorganic materials 0.000 claims description 3
• 229960001055 uracil mustard Drugs 0.000 claims description 3
• FRLDGEVJADJNOZ-UHFFFAOYSA-N 6-hydroxysulfanyl-7h-purine Chemical compound OSC1=NC=NC2=C1NC=N2 FRLDGEVJADJNOZ-UHFFFAOYSA-N 0.000 claims description 2
• 125000004122 cyclic group Chemical group 0.000 claims description 2
• 229930182833 estradiol Natural products 0.000 claims description 2
• 229960005309 estradiol Drugs 0.000 claims description 2
• 208000032839 leukemia Diseases 0.000 claims description 2
• 210000000278 spinal cord Anatomy 0.000 claims description 2
• 208000024891 symptom Diseases 0.000 claims description 2
• 238000002560 therapeutic procedure Methods 0.000 claims description 2
• 125000001960 7 membered carbocyclic group Chemical group 0.000 claims 8
• RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 claims 8
• 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 claims 4
• 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 claims 4
• GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims 4
• GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 claims 4
• 190000008236 Carboplatin Chemical compound 0.000 claims 4
• DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 claims 4
• 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 claims 4
• ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 claims 4
• 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 claims 4
• 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 claims 4
• 108010000817 Leuprolide Proteins 0.000 claims 4
• 229930183665 actinomycin Natural products 0.000 claims 4
• 229960004117 capecitabine Drugs 0.000 claims 4
• 229960005243 carmustine Drugs 0.000 claims 4
• JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims 4
• 229960004630 chlorambucil Drugs 0.000 claims 4
• 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 claims 4
• 229960000975 daunorubicin Drugs 0.000 claims 4
• 229960001904 epirubicin Drugs 0.000 claims 4
• VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 claims 4
• 229960005420 etoposide Drugs 0.000 claims 4
• 229960002074 flutamide Drugs 0.000 claims 4
• 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 claims 4
• 230000003325 follicular Effects 0.000 claims 4
• 229960002913 goserelin Drugs 0.000 claims 4
• 229960000908 idarubicin Drugs 0.000 claims 4
• UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims 4
• 229960003881 letrozole Drugs 0.000 claims 4
• 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 claims 4
• 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 claims 4
• 229960004338 leuprorelin Drugs 0.000 claims 4
• 229960004857 mitomycin Drugs 0.000 claims 4
• NJBFOOCLYDNZJN-UHFFFAOYSA-N pipobroman Chemical compound BrCCC(=O)N1CCN(C(=O)CCBr)CC1 NJBFOOCLYDNZJN-UHFFFAOYSA-N 0.000 claims 4
• 229960000952 pipobroman Drugs 0.000 claims 4
• 229960003387 progesterone Drugs 0.000 claims 4
• 239000000186 progesterone Substances 0.000 claims 4
• 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 claims 4
• 229960001278 teniposide Drugs 0.000 claims 4
• 210000001685 thyroid gland Anatomy 0.000 claims 4
• WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 claims 4
• 229930182834 17alpha-Estradiol Natural products 0.000 claims 3
• GCKMFJBGXUYNAG-UHFFFAOYSA-N 17alpha-methyltestosterone Natural products C1CC2=CC(=O)CCC2(C)C2C1C1CCC(C)(O)C1(C)CC2 GCKMFJBGXUYNAG-UHFFFAOYSA-N 0.000 claims 3
• VOXZDWNPVJITMN-SFFUCWETSA-N 17α-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-SFFUCWETSA-N 0.000 claims 3
• 108010006654 Bleomycin Proteins 0.000 claims 3
• JWBOIMRXGHLCPP-UHFFFAOYSA-N Chloditan Chemical compound C=1C=CC=C(Cl)C=1C(C(Cl)Cl)C1=CC=C(Cl)C=C1 JWBOIMRXGHLCPP-UHFFFAOYSA-N 0.000 claims 3
• GCKMFJBGXUYNAG-HLXURNFRSA-N Methyltestosterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@](C)(O)[C@@]1(C)CC2 GCKMFJBGXUYNAG-HLXURNFRSA-N 0.000 claims 3
• 229910019142 PO4 Inorganic materials 0.000 claims 3
• 208000009956 adenocarcinoma Diseases 0.000 claims 3
• 229960001561 bleomycin Drugs 0.000 claims 3
• 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 claims 3
• GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 claims 3
• 229960005304 fludarabine phosphate Drugs 0.000 claims 3
• 229960001566 methyltestosterone Drugs 0.000 claims 3
• 229960000350 mitotane Drugs 0.000 claims 3
• 239000010452 phosphate Substances 0.000 claims 3
• 230000035935 pregnancy Effects 0.000 claims 3
• VJOHPAMUAGYVFA-UHFFFAOYSA-N 2-n,2-n,4-n,4-n-tetraethyl-1,3,5-triazine-2,4,6-triamine Chemical compound CCN(CC)C1=NC(N)=NC(N(CC)CC)=N1 VJOHPAMUAGYVFA-UHFFFAOYSA-N 0.000 claims 2
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims 2
• 241000219198 Brassica Species 0.000 claims 2
• 235000003351 Brassica cretica Nutrition 0.000 claims 2
• 235000003343 Brassica rupestris Nutrition 0.000 claims 2
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims 2
• QDHHCQZDFGDHMP-UHFFFAOYSA-N Chloramine Chemical compound ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 claims 2
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims 2
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims 2
• 229960002932 anastrozole Drugs 0.000 claims 2
• 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 claims 2
• QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical compound ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 0.000 claims 2
• 239000004202 carbamide Substances 0.000 claims 2
• PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical group NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 claims 2
• NOTIQUSPUUHHEH-UXOVVSIBSA-N dromostanolone propionate Chemical compound C([C@@H]1CC2)C(=O)[C@H](C)C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](OC(=O)CC)[C@@]2(C)CC1 NOTIQUSPUUHHEH-UXOVVSIBSA-N 0.000 claims 2
• 229950004683 drostanolone propionate Drugs 0.000 claims 2
• 229960003276 erythromycin Drugs 0.000 claims 2
• 235000010460 mustard Nutrition 0.000 claims 2
• 229960003087 tioguanine Drugs 0.000 claims 2
• 210000002700 urine Anatomy 0.000 claims 2
• XXFQZUDIYOPKJR-UHFFFAOYSA-N 1-(3,3-dibromopropyl)piperazine Chemical compound BrC(CCN1CCNCC1)Br XXFQZUDIYOPKJR-UHFFFAOYSA-N 0.000 claims 1
• KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 claims 1
• 102100025573 1-alkyl-2-acetylglycerophosphocholine esterase Human genes 0.000 claims 1
• GPVGDGBVGWUGAL-UHFFFAOYSA-N 1-cyclohexyl-1-nitrosourea Chemical compound NC(=O)N(N=O)C1CCCCC1 GPVGDGBVGWUGAL-UHFFFAOYSA-N 0.000 claims 1
• NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 claims 1
• KIXKVUVOLNIKSG-UHFFFAOYSA-N 1-oxo-4,7-dihydroimidazo[4,5-e][1,2,4]thiadiazin-3-amine Chemical compound O=S1NC(N)=NC2=C1NC=N2 KIXKVUVOLNIKSG-UHFFFAOYSA-N 0.000 claims 1
• OXQGTIUCKGYOAA-UHFFFAOYSA-N 2-Ethylbutanoic acid Chemical compound CCC(CC)C(O)=O OXQGTIUCKGYOAA-UHFFFAOYSA-N 0.000 claims 1
• OTDJAMXESTUWLO-UUOKFMHZSA-N 2-amino-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-2-oxolanyl]-3H-purine-6-thione Chemical compound C12=NC(N)=NC(S)=C2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OTDJAMXESTUWLO-UUOKFMHZSA-N 0.000 claims 1
• MMBZCFJKAQZVNI-VPENINKCSA-N 4-amino-5,6-difluoro-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound FC1=C(F)C(N)=NC(=O)N1[C@@H]1O[C@H](CO)[C@@H](O)C1 MMBZCFJKAQZVNI-VPENINKCSA-N 0.000 claims 1
• VHRSUDSXCMQTMA-PJHHCJLFSA-N 6alpha-methylprednisolone Chemical compound C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)CO)CC[C@H]21 VHRSUDSXCMQTMA-PJHHCJLFSA-N 0.000 claims 1
• 108010024976 Asparaginase Proteins 0.000 claims 1
• BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 claims 1
• 241001136616 Methone Species 0.000 claims 1
• 208000000453 Skin Neoplasms Diseases 0.000 claims 1
• PMUIBVMKQVKHBE-UHFFFAOYSA-N [S].NC(N)=O Chemical compound [S].NC(N)=O PMUIBVMKQVKHBE-UHFFFAOYSA-N 0.000 claims 1
• 229910021529 ammonia Inorganic materials 0.000 claims 1
• 230000003471 anti-radiation Effects 0.000 claims 1
• 235000009508 confectionery Nutrition 0.000 claims 1
• 238000006356 dehydrogenation reaction Methods 0.000 claims 1
• BADXJIPKFRBFOT-UHFFFAOYSA-N dimedone Chemical compound CC1(C)CC(=O)CC(=O)C1 BADXJIPKFRBFOT-UHFFFAOYSA-N 0.000 claims 1
• VUUAEBBAUMJPRE-UHFFFAOYSA-N ethyl n-fluorocarbamate Chemical compound CCOC(=O)NF VUUAEBBAUMJPRE-UHFFFAOYSA-N 0.000 claims 1
• 229960000390 fludarabine Drugs 0.000 claims 1
• YLQWCDOCJODRMT-UHFFFAOYSA-N fluoren-9-one Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3C2=C1 YLQWCDOCJODRMT-UHFFFAOYSA-N 0.000 claims 1
• HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 claims 1
• 150000002431 hydrogen Chemical class 0.000 claims 1
• 229930191751 ilexin Natural products 0.000 claims 1
• 150000002576 ketones Chemical class 0.000 claims 1
• 239000012528 membrane Substances 0.000 claims 1
• 230000002175 menstrual effect Effects 0.000 claims 1
• 229950003442 methoprene Drugs 0.000 claims 1
• 229930002897 methoprene Natural products 0.000 claims 1
• 229960004584 methylprednisolone Drugs 0.000 claims 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 1
• WUAPFZMCVAUBPE-UHFFFAOYSA-N rhenium atom Chemical compound [Re] WUAPFZMCVAUBPE-UHFFFAOYSA-N 0.000 claims 1
• 201000000849 skin cancer Diseases 0.000 claims 1
• 239000002246 antineoplastic agent Substances 0.000 abstract description 21
• 229940034982 antineoplastic agent Drugs 0.000 abstract 1
• 239000003528 protein farnesyltransferase inhibitor Substances 0.000 abstract 1
• 125000003118 aryl group Chemical group 0.000 description 214
• 238000011049 filling Methods 0.000 description 162
• 125000001072 heteroaryl group Chemical group 0.000 description 119
• 125000003710 aryl alkyl group Chemical group 0.000 description 96
• 125000001424 substituent group Chemical group 0.000 description 92
• 210000004027 cell Anatomy 0.000 description 91
• 125000000592 heterocycloalkyl group Chemical group 0.000 description 85
• 230000002079 cooperative effect Effects 0.000 description 81
• 150000002367 halogens Chemical group 0.000 description 78
• 229910052736 halogen Chemical group 0.000 description 75
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 65
• 229910052799 carbon Inorganic materials 0.000 description 64
• NIHNNTQXNPWCJQ-UHFFFAOYSA-N o-biphenylenemethane Natural products C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 53
• 238000000034 method Methods 0.000 description 46
• 150000003839 salts Chemical class 0.000 description 45
• 125000003342 alkenyl group Chemical group 0.000 description 41
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 40
• 230000002401 inhibitory effect Effects 0.000 description 38
• 125000000304 alkynyl group Chemical group 0.000 description 37
• 125000004432 carbon atom Chemical group C* 0.000 description 37
• 241000699670 Mus sp. Species 0.000 description 35
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 35
• 125000004446 heteroarylalkyl group Chemical group 0.000 description 34
• 239000012453 solvate Substances 0.000 description 34
• 125000003545 alkoxy group Chemical group 0.000 description 33
• 239000000243 solution Substances 0.000 description 33
• 125000004093 cyano group Chemical group *C#N 0.000 description 32
• RMBPEFMHABBEKP-UHFFFAOYSA-N fluorene Chemical group C1=CC=C2C3=C[CH]C=CC3=CC2=C1 RMBPEFMHABBEKP-UHFFFAOYSA-N 0.000 description 30
• 239000000203 mixture Substances 0.000 description 27
• 231100000673 dose–response relationship Toxicity 0.000 description 26
• 238000007619 statistical method Methods 0.000 description 25
• 239000002585 base Substances 0.000 description 24
• 239000003814 drug Substances 0.000 description 24
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 23
• 230000004083 survival effect Effects 0.000 description 21
• 210000004881 tumor cell Anatomy 0.000 description 21
• 150000001721 carbon Chemical group 0.000 description 20
• 229940127089 cytotoxic agent Drugs 0.000 description 20
• 125000000623 heterocyclic group Chemical group 0.000 description 20
• 230000005764 inhibitory process Effects 0.000 description 20
• 239000003981 vehicle Substances 0.000 description 20
• 229920000858 Cyclodextrin Polymers 0.000 description 18
• 230000004663 cell proliferation Effects 0.000 description 18
• 229940079593 drug Drugs 0.000 description 17
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 17
• 125000004475 heteroaralkyl group Chemical group 0.000 description 16
• 239000002904 solvent Substances 0.000 description 16
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
• 125000003277 amino group Chemical group 0.000 description 14
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 14
• 229940020967 gemzar Drugs 0.000 description 14
• UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 14
• ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 14
• 150000003254 radicals Chemical class 0.000 description 13
• 125000003107 substituted aryl group Chemical group 0.000 description 13
• 241000699666 Mus <mouse, genus> Species 0.000 description 12
• 125000003282 alkyl amino group Chemical group 0.000 description 12
• 238000004458 analytical method Methods 0.000 description 12
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 12
• 230000003993 interaction Effects 0.000 description 12
• 125000004076 pyridyl group Chemical group 0.000 description 12
• 229920006395 saturated elastomer Polymers 0.000 description 12
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 11
• 125000005842 heteroatom Chemical group 0.000 description 11
• 238000000338 in vitro Methods 0.000 description 11
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 11
• 239000000816 peptidomimetic Substances 0.000 description 11
• 150000001204 N-oxides Chemical class 0.000 description 10
• 108090000623 proteins and genes Proteins 0.000 description 10
• 108010014186 ras Proteins Proteins 0.000 description 10
• 102000016914 ras Proteins Human genes 0.000 description 10
• 230000004614 tumor growth Effects 0.000 description 10
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
• 206010013710 Drug interaction Diseases 0.000 description 8
• 125000004448 alkyl carbonyl group Chemical group 0.000 description 8
• 239000002775 capsule Substances 0.000 description 8
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
• 239000004615 ingredient Substances 0.000 description 8
• 239000000843 powder Substances 0.000 description 8
• 238000012545 processing Methods 0.000 description 8
• 239000007787 solid Substances 0.000 description 8
• 239000000126 substance Substances 0.000 description 8
• 125000000547 substituted alkyl group Chemical group 0.000 description 8
• 238000006467 substitution reaction Methods 0.000 description 8
• 238000000134 MTT assay Methods 0.000 description 7
• 231100000002 MTT assay Toxicity 0.000 description 7
• 230000008901 benefit Effects 0.000 description 7
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
• 229910052794 bromium Inorganic materials 0.000 description 7
• 238000002648 combination therapy Methods 0.000 description 7
• 125000004030 farnesyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
• 229930195733 hydrocarbon Natural products 0.000 description 7
• 238000001727 in vivo Methods 0.000 description 7
• 238000007912 intraperitoneal administration Methods 0.000 description 7
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 7
• 238000004445 quantitative analysis Methods 0.000 description 7
• 229910052701 rubidium Inorganic materials 0.000 description 7
• 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 6
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
• 238000003556 assay Methods 0.000 description 6
• 230000010261 cell growth Effects 0.000 description 6
• 125000005885 heterocycloalkylalkyl group Chemical group 0.000 description 6
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
• 230000035755 proliferation Effects 0.000 description 6
• 230000004044 response Effects 0.000 description 6
• 239000000377 silicon dioxide Substances 0.000 description 6
• 239000004215 Carbon black (E152) Substances 0.000 description 5
• 101710113436 GTPase KRas Proteins 0.000 description 5
• 241000282376 Panthera tigris Species 0.000 description 5
• 108090000992 Transferases Proteins 0.000 description 5
• 102000004357 Transferases Human genes 0.000 description 5
• 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 5
• 125000004183 alkoxy alkyl group Chemical group 0.000 description 5
• 230000003042 antagnostic effect Effects 0.000 description 5
• QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 5
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 5
• 210000004268 dentin Anatomy 0.000 description 5
• 238000002474 experimental method Methods 0.000 description 5
• 238000007654 immersion Methods 0.000 description 5
• 230000000670 limiting effect Effects 0.000 description 5
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 5
• 239000006104 solid solution Substances 0.000 description 5
• 230000009044 synergistic interaction Effects 0.000 description 5
• 101100439662 Arabidopsis thaliana CHR5 gene Proteins 0.000 description 4
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical group [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
• 101100402341 Caenorhabditis elegans mpk-1 gene Proteins 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
• 241000124008 Mammalia Species 0.000 description 4
• 108700020796 Oncogene Proteins 0.000 description 4
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
• 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 4
• 230000002159 abnormal effect Effects 0.000 description 4
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical class [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 4
• 230000000259 anti-tumor effect Effects 0.000 description 4
• 150000005840 aryl radicals Chemical class 0.000 description 4
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
• 229960001338 colchicine Drugs 0.000 description 4
• 125000004404 heteroalkyl group Chemical group 0.000 description 4
• 229940088597 hormone Drugs 0.000 description 4
• 239000005556 hormone Substances 0.000 description 4
• 230000001965 increasing effect Effects 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• 210000004072 lung Anatomy 0.000 description 4
• 235000019359 magnesium stearate Nutrition 0.000 description 4
• 230000011278 mitosis Effects 0.000 description 4
• 230000035772 mutation Effects 0.000 description 4
• 229930014626 natural product Natural products 0.000 description 4
• 239000001301 oxygen Substances 0.000 description 4
• 229910052760 oxygen Inorganic materials 0.000 description 4
• 210000002307 prostate Anatomy 0.000 description 4
• RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 4
• 230000002441 reversible effect Effects 0.000 description 4
• 235000012239 silicon dioxide Nutrition 0.000 description 4
• 125000003003 spiro group Chemical group 0.000 description 4
• RWSOTUBLDIXVET-UHFFFAOYSA-O sulfonium Chemical compound [SH3+] RWSOTUBLDIXVET-UHFFFAOYSA-O 0.000 description 4
• 230000002195 synergetic effect Effects 0.000 description 4
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
• YJGVMLPVUAXIQN-LGWHJFRWSA-N (5s,5ar,8ar,9r)-5-hydroxy-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5h-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-LGWHJFRWSA-N 0.000 description 3
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 3
• 125000002373 5 membered heterocyclic group Chemical group 0.000 description 3
• 125000004070 6 membered heterocyclic group Chemical group 0.000 description 3
• VEDTXTNSFWUXGQ-UHFFFAOYSA-N Carbophenothion Chemical group CCOP(=S)(OCC)SCSC1=CC=C(Cl)C=C1 VEDTXTNSFWUXGQ-UHFFFAOYSA-N 0.000 description 3
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
• 102000004190 Enzymes Human genes 0.000 description 3
• 108090000790 Enzymes Proteins 0.000 description 3
• 101100134922 Gallus gallus COR5 gene Proteins 0.000 description 3
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
• WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 3
• 101150020251 NR13 gene Proteins 0.000 description 3
• 108010038807 Oligopeptides Proteins 0.000 description 3
• 102000015636 Oligopeptides Human genes 0.000 description 3
• 102000043276 Oncogene Human genes 0.000 description 3
• 206010061535 Ovarian neoplasm Diseases 0.000 description 3
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• 229940122803 Vinca alkaloid Drugs 0.000 description 3
• 239000004480 active ingredient Substances 0.000 description 3
• 150000001335 aliphatic alkanes Chemical group 0.000 description 3
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
• 230000008485 antagonism Effects 0.000 description 3
• 239000003242 anti bacterial agent Substances 0.000 description 3
• 229940088710 antibiotic agent Drugs 0.000 description 3
• 125000005110 aryl thio group Chemical group 0.000 description 3
• 239000012964 benzotriazole Substances 0.000 description 3
• 239000008280 blood Substances 0.000 description 3
• 210000004369 blood Anatomy 0.000 description 3
• 238000002512 chemotherapy Methods 0.000 description 3
• 210000001072 colon Anatomy 0.000 description 3
• 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 3
• 239000002254 cytotoxic agent Substances 0.000 description 3
• 231100000599 cytotoxic agent Toxicity 0.000 description 3
• 210000005069 ears Anatomy 0.000 description 3
• 239000000839 emulsion Substances 0.000 description 3
• YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 0.000 description 3
• CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 description 3
• 230000006126 farnesylation Effects 0.000 description 3
• 238000009472 formulation Methods 0.000 description 3
• 239000007789 gas Substances 0.000 description 3
• 230000012010 growth Effects 0.000 description 3
• 125000005843 halogen group Chemical group 0.000 description 3
• 150000007857 hydrazones Chemical class 0.000 description 3
• 238000002347 injection Methods 0.000 description 3
• 239000007924 injection Substances 0.000 description 3
• 229910052740 iodine Inorganic materials 0.000 description 3
• 239000007937 lozenge Substances 0.000 description 3
• 238000005259 measurement Methods 0.000 description 3
• 230000000394 mitotic effect Effects 0.000 description 3
• 238000002156 mixing Methods 0.000 description 3
• 230000004048 modification Effects 0.000 description 3
• 238000012986 modification Methods 0.000 description 3
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
• 231100000590 oncogenic Toxicity 0.000 description 3
• 230000002246 oncogenic effect Effects 0.000 description 3
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 3
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
• 229940069328 povidone Drugs 0.000 description 3
• 108090000765 processed proteins & peptides Proteins 0.000 description 3
• 208000023958 prostate neoplasm Diseases 0.000 description 3
• 238000011160 research Methods 0.000 description 3
• 235000015170 shellfish Nutrition 0.000 description 3
• 229940124597 therapeutic agent Drugs 0.000 description 3
• 229910052720 vanadium Inorganic materials 0.000 description 3
• 229960003048 vinblastine Drugs 0.000 description 3
• 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 3
• DLMYFMLKORXJPO-FQEVSTJZSA-N (2R)-2-amino-3-[(triphenylmethyl)thio]propanoic acid Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(SC[C@H](N)C(O)=O)C1=CC=CC=C1 DLMYFMLKORXJPO-FQEVSTJZSA-N 0.000 description 2
• NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 2
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
• DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 2
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
• 125000004648 C2-C8 alkenyl group Chemical group 0.000 description 2
• 125000004649 C2-C8 alkynyl group Chemical group 0.000 description 2
• 101100240516 Caenorhabditis elegans nhr-10 gene Proteins 0.000 description 2
• 101100240522 Caenorhabditis elegans nhr-18 gene Proteins 0.000 description 2
• 208000005623 Carcinogenesis Diseases 0.000 description 2
• 201000009030 Carcinoma Diseases 0.000 description 2
• 241000723346 Cinnamomum camphora Species 0.000 description 2
• 102000004127 Cytokines Human genes 0.000 description 2
• 108090000695 Cytokines Proteins 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• 150000008575 L-amino acids Chemical class 0.000 description 2
• 102100027373 Melanin-concentrating hormone receptor 2 Human genes 0.000 description 2
• 101710089759 Melanin-concentrating hormone receptor 2 Proteins 0.000 description 2
• ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 2
• 241000699660 Mus musculus Species 0.000 description 2
• 125000000815 N-oxide group Chemical group 0.000 description 2
• 206010033128 Ovarian cancer Diseases 0.000 description 2
• 208000025174 PANDAS Diseases 0.000 description 2
• 208000021155 Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection Diseases 0.000 description 2
• 240000004718 Panda Species 0.000 description 2
• 235000016496 Panda oleosa Nutrition 0.000 description 2
• 241001674048 Phthiraptera Species 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 2
• 102000004243 Tubulin Human genes 0.000 description 2
• 108090000704 Tubulin Proteins 0.000 description 2
• GBOGMAARMMDZGR-UHFFFAOYSA-N UNPD149280 Natural products N1C(=O)C23OC(=O)C=CC(O)CCCC(C)CC=CC3C(O)C(=C)C(C)C2C1CC1=CC=CC=C1 GBOGMAARMMDZGR-UHFFFAOYSA-N 0.000 description 2
• 238000002441 X-ray diffraction Methods 0.000 description 2
• 239000002253 acid Substances 0.000 description 2
• DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 2
• 229940059260 amidate Drugs 0.000 description 2
• 125000003368 amide group Chemical group 0.000 description 2
• MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical group [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 2
• RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
• 230000000340 anti-metabolite Effects 0.000 description 2
• 229940100197 antimetabolite Drugs 0.000 description 2
• 239000002256 antimetabolite Substances 0.000 description 2
• 229940041181 antineoplastic drug Drugs 0.000 description 2
• 229910052786 argon Inorganic materials 0.000 description 2
• 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 description 2
• 125000005418 aryl aryl group Chemical group 0.000 description 2
• 125000004104 aryloxy group Chemical group 0.000 description 2
• 230000033228 biological regulation Effects 0.000 description 2
• 230000015572 biosynthetic process Effects 0.000 description 2
• 229930008380 camphor Natural products 0.000 description 2
• 229960000846 camphor Drugs 0.000 description 2
• 230000036952 cancer formation Effects 0.000 description 2
• JHRWWRDRBPCWTF-OLQVQODUSA-N captafol Chemical compound C1C=CC[C@H]2C(=O)N(SC(Cl)(Cl)C(Cl)Cl)C(=O)[C@H]21 JHRWWRDRBPCWTF-OLQVQODUSA-N 0.000 description 2
• AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical group [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 2
• 231100000504 carcinogenesis Toxicity 0.000 description 2
• 239000006143 cell culture medium Substances 0.000 description 2
• NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
• 210000000349 chromosome Anatomy 0.000 description 2
• 239000011248 coating agent Substances 0.000 description 2
• 238000000576 coating method Methods 0.000 description 2
• 239000013256 coordination polymer Chemical group 0.000 description 2
• 238000012937 correction Methods 0.000 description 2
• 150000001924 cycloalkanes Chemical class 0.000 description 2
• 125000000392 cycloalkenyl group Chemical group 0.000 description 2
• DMEGYFMYUHOHGS-UHFFFAOYSA-N cycloheptane Chemical compound C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 2
• GBOGMAARMMDZGR-TYHYBEHESA-N cytochalasin B Chemical compound C([C@H]1[C@@H]2[C@@H](C([C@@H](O)[C@@H]3/C=C/C[C@H](C)CCC[C@@H](O)/C=C/C(=O)O[C@@]23C(=O)N1)=C)C)C1=CC=CC=C1 GBOGMAARMMDZGR-TYHYBEHESA-N 0.000 description 2
• GBOGMAARMMDZGR-JREHFAHYSA-N cytochalasin B Natural products C[C@H]1CCC[C@@H](O)C=CC(=O)O[C@@]23[C@H](C=CC1)[C@H](O)C(=C)[C@@H](C)[C@@H]2[C@H](Cc4ccccc4)NC3=O GBOGMAARMMDZGR-JREHFAHYSA-N 0.000 description 2
• 231100000433 cytotoxic Toxicity 0.000 description 2
• 230000001472 cytotoxic effect Effects 0.000 description 2
• 229960000640 dactinomycin Drugs 0.000 description 2
• RWRIWBAIICGTTQ-UHFFFAOYSA-N difluoromethane Chemical compound FCF RWRIWBAIICGTTQ-UHFFFAOYSA-N 0.000 description 2
• 229960004679 doxorubicin Drugs 0.000 description 2
• 239000003937 drug carrier Substances 0.000 description 2
• 238000011156 evaluation Methods 0.000 description 2
• 235000019197 fats Nutrition 0.000 description 2
• 239000010419 fine particle Substances 0.000 description 2
• SFYLVTNFLRJWTA-UHFFFAOYSA-N fluoren-1-imine Chemical compound C1=CC=C2C3=CC=CC(=N)C3=CC2=C1 SFYLVTNFLRJWTA-UHFFFAOYSA-N 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 125000002350 geranyl group Chemical class [H]C([*])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• 230000009036 growth inhibition Effects 0.000 description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 2
• 125000002883 imidazolyl group Chemical group 0.000 description 2
• 150000002466 imines Chemical class 0.000 description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 239000012669 liquid formulation Substances 0.000 description 2
• 201000009546 lung large cell carcinoma Diseases 0.000 description 2
• 230000003211 malignant effect Effects 0.000 description 2
• 230000001394 metastastic effect Effects 0.000 description 2
• 206010061289 metastatic neoplasm Diseases 0.000 description 2
• 230000001617 migratory effect Effects 0.000 description 2
• 235000013336 milk Nutrition 0.000 description 2
• 239000008267 milk Substances 0.000 description 2
• 210000004080 milk Anatomy 0.000 description 2
• 239000011733 molybdenum Substances 0.000 description 2
• 229910052750 molybdenum Inorganic materials 0.000 description 2
• BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
• 125000006501 nitrophenyl group Chemical group 0.000 description 2
• 238000011580 nude mouse model Methods 0.000 description 2
• 230000002611 ovarian Effects 0.000 description 2
• 125000004043 oxo group Chemical group O=* 0.000 description 2
• 125000000913 palmityl group Chemical class [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])C([H])([H])C([H])([H])[H] 0.000 description 2
• 125000003884 phenylalkyl group Chemical group 0.000 description 2
• ABABQFDOYCEIRS-UHFFFAOYSA-N piperidin-2-ylidenemethanone Chemical class O=C=C1CCCCN1 ABABQFDOYCEIRS-UHFFFAOYSA-N 0.000 description 2
• 125000003386 piperidinyl group Chemical group 0.000 description 2
• 230000037048 polymerization activity Effects 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• 102000004196 processed proteins & peptides Human genes 0.000 description 2
• 229950010131 puromycin Drugs 0.000 description 2
• 108700042226 ras Genes Proteins 0.000 description 2
• OWPCHSCAPHNHAV-QIPOKPRISA-N rhizoxin Chemical compound C/C([C@@H]([C@@H](C)[C@H]1OC(=O)[C@@H]2O[C@H]2C[C@@H]2C[C@@H](OC(=O)C2)[C@H](C)/C=C/[C@H]2O[C@]2(C)[C@@H](O)C1)OC)=C\C=C\C(\C)=C\C1=COC(C)=N1 OWPCHSCAPHNHAV-QIPOKPRISA-N 0.000 description 2
• HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 2
• 238000012216 screening Methods 0.000 description 2
• 230000019491 signal transduction Effects 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 239000007921 spray Substances 0.000 description 2
• 239000008223 sterile water Substances 0.000 description 2
• 150000003431 steroids Chemical class 0.000 description 2
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
• 229910052717 sulfur Inorganic materials 0.000 description 2
• 239000000725 suspension Substances 0.000 description 2
• RCINICONZNJXQF-XAZOAEDWSA-N taxol® Chemical compound O([C@@H]1[C@@]2(CC(C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3(C21)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-XAZOAEDWSA-N 0.000 description 2
• ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical group O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
• 125000003396 thiol group Chemical group [H]S* 0.000 description 2
• 229930192474 thiophene Natural products 0.000 description 2
• 229910052722 tritium Inorganic materials 0.000 description 2
• 229910052721 tungsten Inorganic materials 0.000 description 2
• 230000003442 weekly effect Effects 0.000 description 2
• 210000004885 white matter Anatomy 0.000 description 2
• 239000002023 wood Substances 0.000 description 2
• 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
• QYAPHLRPFNSDNH-MRFRVZCGSA-N (4s,4as,5as,6s,12ar)-7-chloro-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide;hydrochloride Chemical class Cl.C1=CC(Cl)=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O QYAPHLRPFNSDNH-MRFRVZCGSA-N 0.000 description 1
• MSTNYGQPCMXVAQ-RYUDHWBXSA-N (6S)-5,6,7,8-tetrahydrofolic acid Chemical compound C([C@H]1CNC=2N=C(NC(=O)C=2N1)N)NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 MSTNYGQPCMXVAQ-RYUDHWBXSA-N 0.000 description 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
• HCUOEKSZWPGJIM-YBRHCDHNSA-N (e,2e)-2-hydroxyimino-6-methoxy-4-methyl-5-nitrohex-3-enamide Chemical compound COCC([N+]([O-])=O)\C(C)=C\C(=N/O)\C(N)=O HCUOEKSZWPGJIM-YBRHCDHNSA-N 0.000 description 1
• BSNKHEKTRWNNAC-UHFFFAOYSA-N 1,2-Bis(4-nitrophenyl)ethane Chemical compound C1=CC([N+](=O)[O-])=CC=C1CCC1=CC=C([N+]([O-])=O)C=C1 BSNKHEKTRWNNAC-UHFFFAOYSA-N 0.000 description 1
• FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical group C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 1
• KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
• SDCXCAUXZHDIDM-UHFFFAOYSA-N 1-(3-bromopropyl)piperazine Chemical compound BrCCCN1CCNCC1 SDCXCAUXZHDIDM-UHFFFAOYSA-N 0.000 description 1
• ALRLPDGCPYIVHP-UHFFFAOYSA-N 1-nitropyrene Chemical group C1=C2C([N+](=O)[O-])=CC=C(C=C3)C2=C2C3=CC=CC2=C1 ALRLPDGCPYIVHP-UHFFFAOYSA-N 0.000 description 1
• VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
• MQLACMBJVPINKE-UHFFFAOYSA-N 10-[(3-hydroxy-4-methoxyphenyl)methylidene]anthracen-9-one Chemical compound C1=C(O)C(OC)=CC=C1C=C1C2=CC=CC=C2C(=O)C2=CC=CC=C21 MQLACMBJVPINKE-UHFFFAOYSA-N 0.000 description 1
• VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
• CKTSBUTUHBMZGZ-SHYZEUOFSA-N 2'‐deoxycytidine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 CKTSBUTUHBMZGZ-SHYZEUOFSA-N 0.000 description 1
• WHIMJRDDNFCIRZ-UHFFFAOYSA-N 2-cycloheptylpyridine Chemical class C1CCCCCC1C1=CC=CC=N1 WHIMJRDDNFCIRZ-UHFFFAOYSA-N 0.000 description 1
• ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical group OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 1
• LNCCBHFAHILMCT-UHFFFAOYSA-N 2-n,4-n,6-n-triethyl-1,3,5-triazine-2,4,6-triamine Chemical compound CCNC1=NC(NCC)=NC(NCC)=N1 LNCCBHFAHILMCT-UHFFFAOYSA-N 0.000 description 1
• 125000006291 3-hydroxybenzyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(=C1[H])C([H])([H])* 0.000 description 1
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
• 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
• ZUWMBBZBDLJVHD-UHFFFAOYSA-N 5-[1-(2-fluoropyridin-3-yl)-5-methyltriazol-4-yl]-2-propan-2-yl-3h-isoindol-1-one Chemical compound C=1C=C2C(=O)N(C(C)C)CC2=CC=1C(=C1C)N=NN1C1=CC=CN=C1F ZUWMBBZBDLJVHD-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
• 229920001817 Agar Polymers 0.000 description 1
• 101100173726 Arabidopsis thaliana OR23 gene Proteins 0.000 description 1
• 241000239290 Araneae Species 0.000 description 1
• NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical class C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
• 240000007124 Brassica oleracea Species 0.000 description 1
• 101100240521 Caenorhabditis elegans nhr-16 gene Proteins 0.000 description 1
• 101100516563 Caenorhabditis elegans nhr-6 gene Proteins 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 1
• 241000723375 Colchicum Species 0.000 description 1
• 206010048832 Colon adenoma Diseases 0.000 description 1
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
• QASFUMOKHFSJGL-LAFRSMQTSA-N Cyclopamine Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H](CC2=C3C)[C@@H]1[C@@H]2CC[C@@]13O[C@@H]2C[C@H](C)CN[C@H]2[C@H]1C QASFUMOKHFSJGL-LAFRSMQTSA-N 0.000 description 1
• CKTSBUTUHBMZGZ-UHFFFAOYSA-N Deoxycytidine Natural products O=C1N=C(N)C=CN1C1OC(CO)C(O)C1 CKTSBUTUHBMZGZ-UHFFFAOYSA-N 0.000 description 1
• BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical class SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
• 241000196324 Embryophyta Species 0.000 description 1
• 206010051814 Eschar Diseases 0.000 description 1
• 229910052693 Europium Inorganic materials 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 229940123414 Folate antagonist Drugs 0.000 description 1
• 208000004463 Follicular Adenocarcinoma Diseases 0.000 description 1
• 206010064571 Gene mutation Diseases 0.000 description 1
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• 108010026389 Gramicidin Proteins 0.000 description 1
• ZBLLGPUWGCOJNG-UHFFFAOYSA-N Halichondrin B Natural products CC1CC2(CC(C)C3OC4(CC5OC6C(CC5O4)OC7CC8OC9CCC%10OC(CC(C(C9)C8=C)C%11%12CC%13OC%14C(OC%15CCC(CC(=O)OC7C6C)OC%15C%14O%11)C%13O%12)CC%10=C)CC3O2)OC%16OC(CC1%16)C(O)CC(O)CO ZBLLGPUWGCOJNG-UHFFFAOYSA-N 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101000616438 Homo sapiens Microtubule-associated protein 4 Proteins 0.000 description 1
• 101001109689 Homo sapiens Nuclear receptor subfamily 4 group A member 3 Proteins 0.000 description 1
• 101000598778 Homo sapiens Protein OSCP1 Proteins 0.000 description 1
• HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical group CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
• RAXXELZNTBOGNW-UHFFFAOYSA-O Imidazolium Chemical compound C1=C[NH+]=CN1 RAXXELZNTBOGNW-UHFFFAOYSA-O 0.000 description 1
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
• 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 1
• 206010027476 Metastases Diseases 0.000 description 1
• 102100021794 Microtubule-associated protein 4 Human genes 0.000 description 1
• 206010048723 Multiple-drug resistance Diseases 0.000 description 1
• 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 description 1
• 101001067395 Mus musculus Phospholipid scramblase 1 Proteins 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
• 102000034570 NR1 subfamily Human genes 0.000 description 1
• 108020001305 NR1 subfamily Proteins 0.000 description 1
• KYRVNWMVYQXFEU-UHFFFAOYSA-N Nocodazole Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1C(=O)C1=CC=CS1 KYRVNWMVYQXFEU-UHFFFAOYSA-N 0.000 description 1
• 102100022673 Nuclear receptor subfamily 4 group A member 3 Human genes 0.000 description 1
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 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
• CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical class C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 1
• 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 1
• 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 1
• ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
• 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 1
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
• 241000218683 Pseudotsuga Species 0.000 description 1
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
• OWPCHSCAPHNHAV-UHFFFAOYSA-N Rhizoxin Natural products C1C(O)C2(C)OC2C=CC(C)C(OC(=O)C2)CC2CC2OC2C(=O)OC1C(C)C(OC)C(C)=CC=CC(C)=CC1=COC(C)=N1 OWPCHSCAPHNHAV-UHFFFAOYSA-N 0.000 description 1
• 108091006627 SLC12A9 Proteins 0.000 description 1
• 101100212791 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) YBL068W-A gene Proteins 0.000 description 1
• 206010039491 Sarcoma Diseases 0.000 description 1
• 206010041067 Small cell lung cancer Diseases 0.000 description 1
• 102220497176 Small vasohibin-binding protein_T47D_mutation Human genes 0.000 description 1
• 102100036742 Solute carrier family 12 member 9 Human genes 0.000 description 1
• 241000779819 Syncarpia glomulifera Species 0.000 description 1
• 241000270666 Testudines Species 0.000 description 1
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
• 108010021119 Trichosanthin Proteins 0.000 description 1
• 206010047700 Vomiting Diseases 0.000 description 1
• 239000005862 Whey Substances 0.000 description 1
• 102000007544 Whey Proteins Human genes 0.000 description 1
• 108010046377 Whey Proteins Proteins 0.000 description 1
• BQOWUDKEXDCGQS-UHFFFAOYSA-N [CH]1CCCC1 Chemical class [CH]1CCCC1 BQOWUDKEXDCGQS-UHFFFAOYSA-N 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 239000002487 adenosine deaminase inhibitor Substances 0.000 description 1
• 239000000853 adhesive Substances 0.000 description 1
• 230000001070 adhesive effect Effects 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 230000002776 aggregation Effects 0.000 description 1
• 238000004220 aggregation Methods 0.000 description 1
• 235000004279 alanine Nutrition 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 150000001345 alkine derivatives Chemical class 0.000 description 1
• 125000005083 alkoxyalkoxy group Chemical group 0.000 description 1
• 125000002877 alkyl aryl group Chemical group 0.000 description 1
• 125000005037 alkyl phenyl group Chemical group 0.000 description 1
• 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 1
• 150000008052 alkyl sulfonates Chemical class 0.000 description 1
• 229940100198 alkylating agent Drugs 0.000 description 1
• 239000002168 alkylating agent Substances 0.000 description 1
• 125000001118 alkylidene group Chemical group 0.000 description 1
• 125000005282 allenyl group Chemical group 0.000 description 1
• 230000000735 allogeneic effect Effects 0.000 description 1
• KCNKJCHARANTIP-SNAWJCMRSA-N allyl-{4-[3-(4-bromo-phenyl)-benzofuran-6-yloxy]-but-2-enyl}-methyl-amine Chemical group C=1OC2=CC(OC/C=C/CN(CC=C)C)=CC=C2C=1C1=CC=C(Br)C=C1 KCNKJCHARANTIP-SNAWJCMRSA-N 0.000 description 1
• 230000004075 alteration Effects 0.000 description 1
• 235000001014 amino acid Nutrition 0.000 description 1
• 229940024606 amino acid Drugs 0.000 description 1
• 125000000539 amino acid group Chemical group 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 239000005557 antagonist Substances 0.000 description 1
• 230000002942 anti-growth Effects 0.000 description 1
• 230000002927 anti-mitotic effect Effects 0.000 description 1
• 125000002102 aryl alkyloxo group Chemical group 0.000 description 1
• 125000005163 aryl sulfanyl group Chemical group 0.000 description 1
• VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
• XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 1
• 230000003796 beauty Effects 0.000 description 1
• PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 1
• 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
• 230000036765 blood level Effects 0.000 description 1
• 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
• 210000004899 c-terminal region Anatomy 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 239000007963 capsule composition Substances 0.000 description 1
• 125000002837 carbocyclic group Chemical group 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 150000007942 carboxylates Chemical class 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 238000000423 cell based assay Methods 0.000 description 1
• 230000022131 cell cycle Effects 0.000 description 1
• 230000010307 cell transformation Effects 0.000 description 1
• NDAYQJDHGXTBJL-MWWSRJDJSA-N chembl557217 Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](NC(=O)CNC(=O)[C@@H](NC=O)C(C)C)CC(C)C)C(=O)NCCO)=CNC2=C1 NDAYQJDHGXTBJL-MWWSRJDJSA-N 0.000 description 1
• 230000000973 chemotherapeutic effect Effects 0.000 description 1
• 239000012829 chemotherapy agent Substances 0.000 description 1
• 229940044683 chemotherapy drug Drugs 0.000 description 1
• 125000000068 chlorophenyl group Chemical group 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 201000010897 colon adenocarcinoma Diseases 0.000 description 1
• 238000011284 combination treatment Methods 0.000 description 1
• 238000005056 compaction Methods 0.000 description 1
• 230000030944 contact inhibition Effects 0.000 description 1
• 230000008602 contraction Effects 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• WYSYSPBQMXACLI-UHFFFAOYSA-N cycloheptane Chemical compound C1CCC[CH-]CC1 WYSYSPBQMXACLI-UHFFFAOYSA-N 0.000 description 1
• QASFUMOKHFSJGL-UHFFFAOYSA-N cyclopamine Natural products C1C=C2CC(O)CCC2(C)C(CC2=C3C)C1C2CCC13OC2CC(C)CNC2C1C QASFUMOKHFSJGL-UHFFFAOYSA-N 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
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
• 235000018417 cysteine Nutrition 0.000 description 1
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 238000012217 deletion Methods 0.000 description 1
• 230000037430 deletion Effects 0.000 description 1
• CFCUWKMKBJTWLW-UHFFFAOYSA-N deoliosyl-3C-alpha-L-digitoxosyl-MTM Natural products CC=1C(O)=C2C(O)=C3C(=O)C(OC4OC(C)C(O)C(OC5OC(C)C(O)C(OC6OC(C)C(O)C(C)(O)C6)C5)C4)C(C(OC)C(=O)C(O)C(C)O)CC3=CC2=CC=1OC(OC(C)C1O)CC1OC1CC(O)C(O)C(C)O1 CFCUWKMKBJTWLW-UHFFFAOYSA-N 0.000 description 1
• 238000009795 derivation Methods 0.000 description 1
• 238000006477 desulfuration reaction Methods 0.000 description 1
• 230000023556 desulfurization Effects 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 238000003745 diagnosis Methods 0.000 description 1
• WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
• 235000014113 dietary fatty acids Nutrition 0.000 description 1
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 239000000539 dimer Substances 0.000 description 1
• 239000001177 diphosphate Substances 0.000 description 1
• XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
• 235000011180 diphosphates Nutrition 0.000 description 1
• 230000008034 disappearance Effects 0.000 description 1
• 125000000107 disulfanyl group Chemical group [*]SS[H] 0.000 description 1
• OFDNQWIFNXBECV-VFSYNPLYSA-N dolastatin 10 Chemical compound CC(C)[C@H](N(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C=1SC=CN=1)CC1=CC=CC=C1 OFDNQWIFNXBECV-VFSYNPLYSA-N 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• 230000007613 environmental effect Effects 0.000 description 1
• 238000001952 enzyme assay Methods 0.000 description 1
• 210000002745 epiphysis Anatomy 0.000 description 1
• 210000000981 epithelium Anatomy 0.000 description 1
• 229930013356 epothilone Natural products 0.000 description 1
• 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 description 1
• HESCAJZNRMSMJG-KKQRBIROSA-N epothilone A Chemical compound 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 description 1
• 150000003883 epothilone derivatives Chemical class 0.000 description 1
• 231100000333 eschar Toxicity 0.000 description 1
• HQPMKSGTIOYHJT-UHFFFAOYSA-N ethane-1,2-diol;propane-1,2-diol Chemical compound OCCO.CC(O)CO HQPMKSGTIOYHJT-UHFFFAOYSA-N 0.000 description 1
• NPUKDXXFDDZOKR-LLVKDONJSA-N etomidate Chemical compound CCOC(=O)C1=CN=CN1[C@H](C)C1=CC=CC=C1 NPUKDXXFDDZOKR-LLVKDONJSA-N 0.000 description 1
• OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical group [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 1
• 239000000194 fatty acid Substances 0.000 description 1
• 229930195729 fatty acid Natural products 0.000 description 1
• 230000002349 favourable effect Effects 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 125000002519 galactosyl group Chemical group C1([C@H](O)[C@@H](O)[C@@H](O)[C@H](O1)CO)* 0.000 description 1
• 230000014509 gene expression Effects 0.000 description 1
• 125000002686 geranylgeranyl group Chemical group [H]C([*])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 1
• 229930182470 glycoside Natural products 0.000 description 1
• 150000002338 glycosides Chemical class 0.000 description 1
• 125000003147 glycosyl group Chemical group 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• FXNFULJVOQMBCW-VZBLNRDYSA-N halichondrin b Chemical compound O([C@@H]1[C@@H](C)[C@@H]2O[C@@H]3C[C@@]4(O[C@H]5[C@@H](C)C[C@@]6(C[C@@H]([C@@H]7O[C@@H](C[C@@H]7O6)[C@@H](O)C[C@@H](O)CO)C)O[C@H]5C4)O[C@@H]3C[C@@H]2O[C@H]1C[C@@H]1C(=C)[C@H](C)C[C@@H](O1)CC[C@H]1C(=C)C[C@@H](O1)CC1)C(=O)C[C@H](O2)CC[C@H]3[C@H]2[C@H](O2)[C@@H]4O[C@@H]5C[C@@]21O[C@@H]5[C@@H]4O3 FXNFULJVOQMBCW-VZBLNRDYSA-N 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 201000010536 head and neck cancer Diseases 0.000 description 1
• 208000014829 head and neck neoplasm Diseases 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 125000005343 heterocyclic alkyl group Chemical group 0.000 description 1
• 239000008240 homogeneous mixture Substances 0.000 description 1
• 208000018821 hormone-resistant prostate carcinoma Diseases 0.000 description 1
• 125000001183 hydrocarbyl group Chemical group 0.000 description 1
• CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
• 150000002460 imidazoles Chemical class 0.000 description 1
• 239000007943 implant Substances 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 238000000099 in vitro assay Methods 0.000 description 1
• 238000005462 in vivo assay Methods 0.000 description 1
• 238000012750 in vivo screening Methods 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 238000012482 interaction analysis Methods 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 239000007928 intraperitoneal injection Substances 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 239000010977 jade Substances 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 229960003088 loratadine Drugs 0.000 description 1
• JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 201000005249 lung adenocarcinoma Diseases 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
• 239000001095 magnesium carbonate Substances 0.000 description 1
• 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• WKPWGQKGSOKKOO-RSFHAFMBSA-N maytansine Chemical compound CO[C@@H]([C@@]1(O)C[C@](OC(=O)N1)([C@H]([C@@H]1O[C@@]1(C)[C@@H](OC(=O)[C@H](C)N(C)C(C)=O)CC(=O)N1C)C)[H])\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 WKPWGQKGSOKKOO-RSFHAFMBSA-N 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 229960003194 meglumine Drugs 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000009401 metastasis Effects 0.000 description 1
• MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
• 229930182817 methionine Natural products 0.000 description 1
• UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
• 230000005012 migration Effects 0.000 description 1
• 238000013508 migration Methods 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
• 150000002773 monoterpene derivatives Chemical group 0.000 description 1
• 229960005181 morphine Drugs 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• 238000010172 mouse model Methods 0.000 description 1
• VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
• CMEGANPVAXDBPL-INIZCTEOSA-N n-[(7s)-1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-6,7-dihydro-5h-benzo[a]heptalen-7-yl]acetamide Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(SC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC CMEGANPVAXDBPL-INIZCTEOSA-N 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 210000005036 nerve Anatomy 0.000 description 1
• CMUOJBJRZUHRMU-UHFFFAOYSA-N nitrourea Chemical compound NC(=O)N[N+]([O-])=O CMUOJBJRZUHRMU-UHFFFAOYSA-N 0.000 description 1
• 229950006344 nocodazole Drugs 0.000 description 1
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
• 210000004940 nucleus Anatomy 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 230000002018 overexpression Effects 0.000 description 1
• 238000007254 oxidation 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
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• UOJMTSCORVQOHS-UHFFFAOYSA-N pachypodol Natural products COc1cc(ccc1O)C2=C(C)C(=O)c3c(O)cc(C)cc3O2 UOJMTSCORVQOHS-UHFFFAOYSA-N 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 125000005328 phosphinyl group Chemical group [PH2](=O)* 0.000 description 1
• 229930006728 pinane Natural products 0.000 description 1
• XOKSLPVRUOBDEW-UHFFFAOYSA-N pinane of uncertain configuration Natural products CC1CCC2C(C)(C)C1C2 XOKSLPVRUOBDEW-UHFFFAOYSA-N 0.000 description 1
• 239000001739 pinus spp. Substances 0.000 description 1
• 210000002706 plastid Anatomy 0.000 description 1
• 229960003171 plicamycin Drugs 0.000 description 1
• 229920001993 poloxamer 188 Polymers 0.000 description 1
• 239000008389 polyethoxylated castor oil Substances 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 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
• 229960000624 procarbazine Drugs 0.000 description 1
• 238000003672 processing method Methods 0.000 description 1
• ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
• 235000004252 protein component Nutrition 0.000 description 1
• 235000018102 proteins Nutrition 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 150000003212 purines Chemical class 0.000 description 1
• 150000003230 pyrimidines Chemical class 0.000 description 1
• 230000006340 racemization Effects 0.000 description 1
• 230000002829 reductive effect Effects 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 230000008844 regulatory mechanism Effects 0.000 description 1
• BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
• 230000008439 repair process Effects 0.000 description 1
• 230000000717 retained effect Effects 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 102220030673 rs59931416 Human genes 0.000 description 1
• 210000003079 salivary gland Anatomy 0.000 description 1
• 230000035945 sensitivity Effects 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 150000003354 serine derivatives Chemical class 0.000 description 1
• 208000000587 small cell lung carcinoma Diseases 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 239000007909 solid dosage form Substances 0.000 description 1
• 238000007711 solidification Methods 0.000 description 1
• 230000008023 solidification Effects 0.000 description 1
• 235000014347 soups Nutrition 0.000 description 1
• 230000020347 spindle assembly Effects 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 238000003756 stirring Methods 0.000 description 1
• 239000011550 stock solution Substances 0.000 description 1
• 239000004575 stone Substances 0.000 description 1
• 125000000565 sulfonamide group Chemical group 0.000 description 1
• 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 239000005460 tetrahydrofolate Substances 0.000 description 1
• 150000003536 tetrazoles Chemical class 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 208000030901 thyroid gland follicular carcinoma Diseases 0.000 description 1
• 208000027031 thyroid symptom Diseases 0.000 description 1
• 229940098465 tincture Drugs 0.000 description 1
• 238000012549 training Methods 0.000 description 1
• 230000009261 transgenic effect Effects 0.000 description 1
• 238000011830 transgenic mouse model Methods 0.000 description 1
• 125000004665 trialkylsilyl group Chemical group 0.000 description 1
• ZBZJXHCVGLJWFG-UHFFFAOYSA-N trichloromethyl(.) Chemical compound Cl[C](Cl)Cl ZBZJXHCVGLJWFG-UHFFFAOYSA-N 0.000 description 1
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
• 229940036248 turpentine Drugs 0.000 description 1
• KDQAABAKXDWYSZ-JKDPCDLQSA-N vincaleukoblastine sulfate Chemical compound OS(O)(=O)=O.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)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 KDQAABAKXDWYSZ-JKDPCDLQSA-N 0.000 description 1
• AQTQHPDCURKLKT-JKDPCDLQSA-N vincristine sulfate Chemical compound OS(O)(=O)=O.C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C=O)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 AQTQHPDCURKLKT-JKDPCDLQSA-N 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 230000008673 vomiting Effects 0.000 description 1
• 238000003260 vortexing Methods 0.000 description 1
• 229940033942 zoladex Drugs 0.000 description 1