CA2539320A1 - Use of chk1 inhibitors to control cell proliferation - Google Patents
Use of chk1 inhibitors to control cell proliferation Download PDFInfo
- Publication number
- CA2539320A1 CA2539320A1 CA002539320A CA2539320A CA2539320A1 CA 2539320 A1 CA2539320 A1 CA 2539320A1 CA 002539320 A CA002539320 A CA 002539320A CA 2539320 A CA2539320 A CA 2539320A CA 2539320 A1 CA2539320 A1 CA 2539320A1
- Authority
- CA
- Canada
- Prior art keywords
- substituted
- unsubstituted
- groups
- alkyl
- heterocyclyl
- 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.)
- Abandoned
Links
- 239000003112 inhibitor Substances 0.000 title claims abstract description 125
- 230000004663 cell proliferation Effects 0.000 title claims abstract description 30
- 101150050673 CHK1 gene Proteins 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 105
- 239000012190 activator Substances 0.000 claims abstract description 100
- 101150113535 chek1 gene Proteins 0.000 claims abstract description 62
- 230000002062 proliferating effect Effects 0.000 claims abstract description 51
- 230000025084 cell cycle arrest Effects 0.000 claims abstract description 34
- 230000001594 aberrant effect Effects 0.000 claims abstract description 27
- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 17
- 229940127089 cytotoxic agent Drugs 0.000 claims abstract description 14
- 210000004027 cell Anatomy 0.000 claims description 215
- -1 platinum coordination complex Chemical class 0.000 claims description 101
- 206010028980 Neoplasm Diseases 0.000 claims description 95
- 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 38
- 229960005277 gemcitabine Drugs 0.000 claims description 38
- 230000000694 effects Effects 0.000 claims description 34
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 28
- 201000011510 cancer Diseases 0.000 claims description 27
- 239000003795 chemical substances by application Substances 0.000 claims description 26
- 210000004881 tumor cell Anatomy 0.000 claims description 22
- 230000012820 cell cycle checkpoint Effects 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 18
- 230000005855 radiation Effects 0.000 claims description 18
- 230000011278 mitosis Effects 0.000 claims description 14
- 108090000623 proteins and genes Proteins 0.000 claims description 12
- 210000001519 tissue Anatomy 0.000 claims description 12
- 208000026310 Breast neoplasm Diseases 0.000 claims description 11
- 230000012010 growth Effects 0.000 claims description 11
- 206010006187 Breast cancer Diseases 0.000 claims description 10
- 206010033128 Ovarian cancer Diseases 0.000 claims description 10
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 10
- 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 9
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 9
- 229960004316 cisplatin Drugs 0.000 claims description 9
- 230000005764 inhibitory process Effects 0.000 claims description 9
- 206010005003 Bladder cancer Diseases 0.000 claims description 8
- 201000009030 Carcinoma Diseases 0.000 claims description 8
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 claims description 8
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 8
- 239000012829 chemotherapy agent Substances 0.000 claims description 8
- 238000001727 in vivo Methods 0.000 claims description 8
- 208000020816 lung neoplasm Diseases 0.000 claims description 8
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 8
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 8
- 102000004169 proteins and genes Human genes 0.000 claims description 8
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 7
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 7
- 230000000340 anti-metabolite Effects 0.000 claims description 7
- 229940100197 antimetabolite Drugs 0.000 claims description 7
- 239000002256 antimetabolite Substances 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 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 7
- 230000003439 radiotherapeutic effect Effects 0.000 claims description 7
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 7
- FPVKHBSQESCIEP-UHFFFAOYSA-N (8S)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol Natural products C1C(O)C(CO)OC1N1C(NC=NCC2O)=C2N=C1 FPVKHBSQESCIEP-UHFFFAOYSA-N 0.000 claims description 6
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 6
- 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 6
- 206010029260 Neuroblastoma Diseases 0.000 claims description 6
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 claims description 6
- 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 claims description 6
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 claims description 6
- 229960005420 etoposide Drugs 0.000 claims description 6
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical class 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 description 6
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 claims description 6
- 206010061289 metastatic neoplasm Diseases 0.000 claims description 6
- 229960000485 methotrexate Drugs 0.000 claims description 6
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical group CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 claims description 6
- 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 6
- 150000003230 pyrimidines Chemical class 0.000 claims description 6
- 239000000523 sample Substances 0.000 claims description 6
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical group CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 claims description 5
- FVLVBPDQNARYJU-XAHDHGMMSA-N C[C@H]1CCC(CC1)NC(=O)N(CCCl)N=O Chemical compound C[C@H]1CCC(CC1)NC(=O)N(CCCl)N=O FVLVBPDQNARYJU-XAHDHGMMSA-N 0.000 claims description 5
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 claims description 5
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 5
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 5
- 206010018338 Glioma Diseases 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
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 5
- 206010025323 Lymphomas Diseases 0.000 claims description 5
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 5
- 201000004681 Psoriasis Diseases 0.000 claims description 5
- 208000024313 Testicular Neoplasms Diseases 0.000 claims description 5
- 229960000473 altretamine Drugs 0.000 claims description 5
- 229960002949 fluorouracil Drugs 0.000 claims description 5
- 208000014018 liver neoplasm Diseases 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 229960004961 mechlorethamine Drugs 0.000 claims description 5
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 claims description 5
- 201000001441 melanoma Diseases 0.000 claims description 5
- 229930014626 natural product Natural products 0.000 claims description 5
- 201000008968 osteosarcoma Diseases 0.000 claims description 5
- 229910052697 platinum Inorganic materials 0.000 claims description 5
- 229960003440 semustine Drugs 0.000 claims description 5
- IUCJMVBFZDHPDX-UHFFFAOYSA-N tretamine Chemical group C1CN1C1=NC(N2CC2)=NC(N2CC2)=N1 IUCJMVBFZDHPDX-UHFFFAOYSA-N 0.000 claims description 5
- 229950001353 tretamine Drugs 0.000 claims description 5
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 4
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 4
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims 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 claims description 4
- 208000022072 Gallbladder Neoplasms Diseases 0.000 claims description 4
- 208000017604 Hodgkin disease Diseases 0.000 claims description 4
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical group NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 claims description 4
- 208000002471 Penile Neoplasms Diseases 0.000 claims description 4
- 208000002158 Proliferative Vitreoretinopathy Diseases 0.000 claims description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 4
- 201000000582 Retinoblastoma Diseases 0.000 claims description 4
- 206010038934 Retinopathy proliferative Diseases 0.000 claims 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 claims description 4
- 229940122803 Vinca alkaloid Drugs 0.000 claims description 4
- 229960004562 carboplatin Drugs 0.000 claims description 4
- 208000029742 colonic neoplasm Diseases 0.000 claims description 4
- 229960004397 cyclophosphamide Drugs 0.000 claims description 4
- 239000003534 dna topoisomerase inhibitor Substances 0.000 claims description 4
- 150000002224 folic acids Chemical class 0.000 claims description 4
- 229960001330 hydroxycarbamide Drugs 0.000 claims description 4
- 210000004072 lung Anatomy 0.000 claims description 4
- 208000021971 neovascular inflammatory vitreoretinopathy Diseases 0.000 claims description 4
- 229960005079 pemetrexed Drugs 0.000 claims description 4
- 230000006785 proliferative vitreoretinopathy Effects 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 208000000649 small cell carcinoma Diseases 0.000 claims description 4
- WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 claims description 4
- 229940044693 topoisomerase inhibitor Drugs 0.000 claims description 4
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 claims description 4
- 229960000303 topotecan Drugs 0.000 claims description 4
- 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 claims description 4
- CTRPRMNBTVRDFH-UHFFFAOYSA-N 2-n-methyl-1,3,5-triazine-2,4,6-triamine Chemical compound CNC1=NC(N)=NC(N)=N1 CTRPRMNBTVRDFH-UHFFFAOYSA-N 0.000 claims description 3
- KISUPFXQEHWGAR-RRKCRQDMSA-N 4-amino-5-bromo-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound C1=C(Br)C(N)=NC(=O)N1[C@@H]1O[C@H](CO)[C@@H](O)C1 KISUPFXQEHWGAR-RRKCRQDMSA-N 0.000 claims description 3
- NMUSYJAQQFHJEW-UHFFFAOYSA-N 5-Azacytidine Natural products O=C1N=C(N)N=CN1C1C(O)C(O)C(CO)O1 NMUSYJAQQFHJEW-UHFFFAOYSA-N 0.000 claims description 3
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 claims description 3
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical group C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 3
- 108010006654 Bleomycin Proteins 0.000 claims description 3
- 108010092160 Dactinomycin Proteins 0.000 claims description 3
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 3
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 claims description 3
- 208000003456 Juvenile Arthritis Diseases 0.000 claims description 3
- 206010027406 Mesothelioma Diseases 0.000 claims description 3
- 206010027476 Metastases Diseases 0.000 claims description 3
- 208000034578 Multiple myelomas Diseases 0.000 claims description 3
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims description 3
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 3
- 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 claims description 3
- 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 claims description 3
- 150000008052 alkyl sulfonates Chemical group 0.000 claims description 3
- 229940100198 alkylating agent Drugs 0.000 claims description 3
- 239000002168 alkylating agent Substances 0.000 claims description 3
- 239000003242 anti bacterial agent Substances 0.000 claims description 3
- 230000003432 anti-folate effect Effects 0.000 claims description 3
- 229940127074 antifolate Drugs 0.000 claims description 3
- 229960002756 azacitidine Drugs 0.000 claims description 3
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 claims description 3
- 229960002170 azathioprine Drugs 0.000 claims description 3
- 239000012472 biological sample Substances 0.000 claims description 3
- 229960001561 bleomycin Drugs 0.000 claims description 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 description 3
- 229960005243 carmustine Drugs 0.000 claims description 3
- 239000003638 chemical reducing agent Substances 0.000 claims description 3
- 229960004630 chlorambucil Drugs 0.000 claims description 3
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims description 3
- 229960002436 cladribine Drugs 0.000 claims description 3
- 229960000684 cytarabine Drugs 0.000 claims description 3
- 229960000640 dactinomycin Drugs 0.000 claims description 3
- 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 3
- 239000004052 folic acid antagonist Substances 0.000 claims description 3
- 201000009277 hairy cell leukemia Diseases 0.000 claims description 3
- 229960001101 ifosfamide Drugs 0.000 claims description 3
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 claims description 3
- 229960004768 irinotecan Drugs 0.000 claims description 3
- 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 description 3
- 229960002247 lomustine Drugs 0.000 claims description 3
- 229960001924 melphalan Drugs 0.000 claims description 3
- 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 3
- 229960001428 mercaptopurine Drugs 0.000 claims description 3
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 claims description 3
- 229960001756 oxaliplatin Drugs 0.000 claims description 3
- 229960002340 pentostatin Drugs 0.000 claims description 3
- 229960000624 procarbazine Drugs 0.000 claims description 3
- 150000003212 purines Chemical class 0.000 claims description 3
- 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 description 3
- 229960001278 teniposide Drugs 0.000 claims description 3
- 229960001196 thiotepa Drugs 0.000 claims description 3
- 229960001099 trimetrexate Drugs 0.000 claims description 3
- NOYPYLRCIDNJJB-UHFFFAOYSA-N trimetrexate Chemical compound COC1=C(OC)C(OC)=CC(NCC=2C(=C3C(N)=NC(N)=NC3=CC=2)C)=C1 NOYPYLRCIDNJJB-UHFFFAOYSA-N 0.000 claims description 3
- 208000029387 trophoblastic neoplasm Diseases 0.000 claims description 3
- 208000013139 vaginal neoplasm Diseases 0.000 claims description 3
- 229960003048 vinblastine Drugs 0.000 claims description 3
- 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 3
- 229960004528 vincristine Drugs 0.000 claims description 3
- 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 3
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 claims description 3
- 229960002066 vinorelbine Drugs 0.000 claims description 3
- FBDOJYYTMIHHDH-OZBJMMHXSA-N (19S)-19-ethyl-19-hydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-2,4,6,8,10,14,20-heptaen-18-one Chemical group CC[C@@]1(O)C(=O)OCC2=CN3Cc4cc5ccccc5nc4C3C=C12 FBDOJYYTMIHHDH-OZBJMMHXSA-N 0.000 claims description 2
- 206010003445 Ascites Diseases 0.000 claims description 2
- 201000001320 Atherosclerosis Diseases 0.000 claims description 2
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical group CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims description 2
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 claims description 2
- 208000006402 Ductal Carcinoma Diseases 0.000 claims description 2
- 206010063045 Effusion Diseases 0.000 claims description 2
- 208000006168 Ewing Sarcoma Diseases 0.000 claims description 2
- 208000006050 Hemangiopericytoma Diseases 0.000 claims description 2
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims description 2
- 208000007766 Kaposi sarcoma Diseases 0.000 claims description 2
- 208000002260 Keloid Diseases 0.000 claims description 2
- 206010023330 Keloid scar Diseases 0.000 claims description 2
- 206010061523 Lip and/or oral cavity cancer Diseases 0.000 claims description 2
- 208000007433 Lymphatic Metastasis Diseases 0.000 claims description 2
- 206010026673 Malignant Pleural Effusion Diseases 0.000 claims description 2
- 206010061309 Neoplasm progression Diseases 0.000 claims description 2
- 208000034179 Neoplasms, Glandular and Epithelial Diseases 0.000 claims description 2
- 206010061534 Oesophageal squamous cell carcinoma Diseases 0.000 claims description 2
- 208000001132 Osteoporosis Diseases 0.000 claims description 2
- 206010065857 Primary Effusion Lymphoma Diseases 0.000 claims description 2
- 208000017442 Retinal disease Diseases 0.000 claims description 2
- 206010038923 Retinopathy Diseases 0.000 claims description 2
- 208000036765 Squamous cell carcinoma of the esophagus Diseases 0.000 claims description 2
- 206010042033 Stevens-Johnson syndrome Diseases 0.000 claims description 2
- 231100000168 Stevens-Johnson syndrome Toxicity 0.000 claims description 2
- 208000002495 Uterine Neoplasms Diseases 0.000 claims description 2
- 206010047115 Vasculitis Diseases 0.000 claims description 2
- 208000009621 actinic keratosis Diseases 0.000 claims description 2
- 210000004404 adrenal cortex Anatomy 0.000 claims description 2
- 210000003567 ascitic fluid Anatomy 0.000 claims description 2
- 229960002092 busulfan Drugs 0.000 claims description 2
- 230000004709 cell invasion Effects 0.000 claims description 2
- 210000003169 central nervous system Anatomy 0.000 claims description 2
- 208000019065 cervical carcinoma Diseases 0.000 claims description 2
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 claims description 2
- 229960000258 corticotropin Drugs 0.000 claims description 2
- 229960003901 dacarbazine Drugs 0.000 claims description 2
- 229960004679 doxorubicin Drugs 0.000 claims description 2
- 208000007276 esophageal squamous cell carcinoma Diseases 0.000 claims description 2
- 239000012530 fluid Substances 0.000 claims description 2
- 230000003463 hyperproliferative effect Effects 0.000 claims description 2
- 206010021198 ichthyosis Diseases 0.000 claims description 2
- 210000001117 keloid Anatomy 0.000 claims description 2
- 210000002510 keratinocyte Anatomy 0.000 claims description 2
- 208000017169 kidney disease Diseases 0.000 claims description 2
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 claims description 2
- 230000009826 neoplastic cell growth Effects 0.000 claims description 2
- 201000008383 nephritis Diseases 0.000 claims description 2
- 208000008798 osteoma Diseases 0.000 claims description 2
- 210000002394 ovarian follicle Anatomy 0.000 claims description 2
- 208000003154 papilloma Diseases 0.000 claims description 2
- 239000003504 photosensitizing agent Substances 0.000 claims description 2
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 claims description 2
- 208000037803 restenosis Diseases 0.000 claims description 2
- 230000037390 scarring Effects 0.000 claims description 2
- 208000017520 skin disease Diseases 0.000 claims description 2
- 206010041823 squamous cell carcinoma Diseases 0.000 claims description 2
- 208000017572 squamous cell neoplasm Diseases 0.000 claims description 2
- 230000001360 synchronised effect Effects 0.000 claims description 2
- 201000002341 thymus lymphoma Diseases 0.000 claims description 2
- 229960003087 tioguanine Drugs 0.000 claims description 2
- 206010044412 transitional cell carcinoma Diseases 0.000 claims description 2
- 230000005751 tumor progression Effects 0.000 claims description 2
- 210000003905 vulva Anatomy 0.000 claims description 2
- 239000002534 radiation-sensitizing agent Substances 0.000 claims 3
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical group C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 claims 2
- 230000003115 biocidal effect Effects 0.000 claims 2
- OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical group NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 claims 2
- 208000037062 Polyps Diseases 0.000 claims 1
- 208000024770 Thyroid neoplasm Diseases 0.000 claims 1
- 230000003140 astrocytic effect Effects 0.000 claims 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 claims 1
- 208000037819 metastatic cancer Diseases 0.000 claims 1
- 208000011575 metastatic malignant neoplasm Diseases 0.000 claims 1
- 201000008026 nephroblastoma Diseases 0.000 claims 1
- QOFFJEBXNKRSPX-ZDUSSCGKSA-N pemetrexed Chemical compound C1=N[C]2NC(N)=NC(=O)C2=C1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 QOFFJEBXNKRSPX-ZDUSSCGKSA-N 0.000 claims 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims 1
- 230000030833 cell death Effects 0.000 abstract description 11
- 230000002401 inhibitory effect Effects 0.000 abstract description 9
- 230000001225 therapeutic effect Effects 0.000 abstract description 9
- 230000001976 improved effect Effects 0.000 abstract description 2
- 125000000217 alkyl group Chemical group 0.000 description 757
- 125000000623 heterocyclic group Chemical group 0.000 description 229
- 125000003118 aryl group Chemical group 0.000 description 227
- 101150006084 CHKB gene Proteins 0.000 description 188
- 125000001072 heteroaryl group Chemical group 0.000 description 150
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 148
- 229910052739 hydrogen Inorganic materials 0.000 description 135
- 229910052757 nitrogen Inorganic materials 0.000 description 120
- 125000000753 cycloalkyl group Chemical group 0.000 description 117
- 239000001257 hydrogen Substances 0.000 description 113
- 125000004103 aminoalkyl group Chemical group 0.000 description 111
- 150000001875 compounds Chemical class 0.000 description 109
- 229910020008 S(O) Inorganic materials 0.000 description 108
- 125000003277 amino group Chemical group 0.000 description 106
- 125000003342 alkenyl group Chemical group 0.000 description 102
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 101
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 96
- 125000003545 alkoxy group Chemical group 0.000 description 95
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 93
- 125000000304 alkynyl group Chemical group 0.000 description 86
- 125000004093 cyano group Chemical group *C#N 0.000 description 83
- 125000004432 carbon atom Chemical group C* 0.000 description 81
- 125000004104 aryloxy group Chemical group 0.000 description 72
- 125000005843 halogen group Chemical group 0.000 description 70
- 125000003710 aryl alkyl group Chemical group 0.000 description 66
- 125000004415 heterocyclylalkyl group Chemical group 0.000 description 64
- 229910052760 oxygen Inorganic materials 0.000 description 63
- 235000002639 sodium chloride Nutrition 0.000 description 55
- 150000003839 salts Chemical class 0.000 description 53
- 229910052717 sulfur Inorganic materials 0.000 description 53
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 51
- 125000001589 carboacyl group Chemical group 0.000 description 51
- 229910052736 halogen Inorganic materials 0.000 description 47
- 150000002367 halogens Chemical class 0.000 description 47
- 238000011282 treatment Methods 0.000 description 46
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 45
- 125000002877 alkyl aryl group Chemical group 0.000 description 44
- 125000005844 heterocyclyloxy group Chemical group 0.000 description 43
- 125000005213 alkyl heteroaryl group Chemical group 0.000 description 42
- 230000022131 cell cycle Effects 0.000 description 41
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 41
- 229910052799 carbon Inorganic materials 0.000 description 40
- 125000001424 substituent group Chemical group 0.000 description 39
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 37
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 34
- 239000001301 oxygen Substances 0.000 description 33
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 32
- 125000004663 dialkyl amino group Chemical group 0.000 description 32
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 32
- 125000005553 heteroaryloxy group Chemical group 0.000 description 32
- 230000018199 S phase Effects 0.000 description 30
- 125000005842 heteroatom Chemical group 0.000 description 27
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 27
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 24
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 24
- 125000001931 aliphatic group Chemical group 0.000 description 24
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 24
- 239000011593 sulfur Substances 0.000 description 24
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 22
- 229940002612 prodrug Drugs 0.000 description 22
- 239000000651 prodrug Substances 0.000 description 22
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 21
- 125000000278 alkyl amino alkyl group Chemical group 0.000 description 20
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 19
- 125000003282 alkyl amino group Chemical group 0.000 description 18
- 125000001691 aryl alkyl amino group Chemical group 0.000 description 18
- 208000035475 disorder Diseases 0.000 description 18
- 125000001145 hydrido group Chemical group *[H] 0.000 description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 18
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 17
- 238000003556 assay Methods 0.000 description 17
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 16
- 206010070834 Sensitisation Diseases 0.000 description 16
- 125000005127 aryl alkoxy alkyl group Chemical group 0.000 description 16
- 230000008313 sensitization Effects 0.000 description 16
- 125000005128 aryl amino alkyl group Chemical group 0.000 description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 15
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 14
- 230000005778 DNA damage Effects 0.000 description 14
- 231100000277 DNA damage Toxicity 0.000 description 14
- 125000005083 alkoxyalkoxy group Chemical group 0.000 description 14
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 12
- 108010009583 Transforming Growth Factors Proteins 0.000 description 12
- 102000009618 Transforming Growth Factors Human genes 0.000 description 12
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 12
- 229940127093 camptothecin Drugs 0.000 description 12
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 12
- 125000004193 piperazinyl group Chemical group 0.000 description 12
- 239000000460 chlorine Substances 0.000 description 11
- 238000011260 co-administration Methods 0.000 description 11
- 125000000392 cycloalkenyl group Chemical group 0.000 description 11
- 230000005865 ionizing radiation Effects 0.000 description 11
- 239000002207 metabolite Substances 0.000 description 11
- 125000004433 nitrogen atom Chemical group N* 0.000 description 11
- 125000001118 alkylidene group Chemical group 0.000 description 10
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 10
- 150000001721 carbon Chemical group 0.000 description 10
- 229910052731 fluorine Inorganic materials 0.000 description 10
- 125000001188 haloalkyl group Chemical group 0.000 description 10
- 125000004076 pyridyl group Chemical group 0.000 description 10
- 101100295738 Gallus gallus COR3 gene Proteins 0.000 description 9
- 108020000002 NR3 subfamily Proteins 0.000 description 9
- 108091000080 Phosphotransferase Proteins 0.000 description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 9
- 102000020233 phosphotransferase Human genes 0.000 description 9
- 230000035755 proliferation Effects 0.000 description 9
- 231100001274 therapeutic index Toxicity 0.000 description 9
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 8
- 125000004429 atom Chemical group 0.000 description 8
- 206010017758 gastric cancer Diseases 0.000 description 8
- 230000007246 mechanism Effects 0.000 description 8
- 239000012453 solvate Substances 0.000 description 8
- 101150012716 CDK1 gene Proteins 0.000 description 7
- 101100059559 Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) nimX gene Proteins 0.000 description 7
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 7
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 7
- 206010061535 Ovarian neoplasm Diseases 0.000 description 7
- 101100273808 Xenopus laevis cdk1-b gene Proteins 0.000 description 7
- 239000004202 carbamide Substances 0.000 description 7
- 229940126864 fibroblast growth factor Drugs 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 230000000394 mitotic effect Effects 0.000 description 7
- 125000004430 oxygen atom Chemical group O* 0.000 description 7
- 201000011549 stomach cancer Diseases 0.000 description 7
- 102000004127 Cytokines Human genes 0.000 description 6
- 108090000695 Cytokines Proteins 0.000 description 6
- 230000012746 DNA damage checkpoint Effects 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 230000010337 G2 phase Effects 0.000 description 6
- 230000027311 M phase Effects 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 206010039491 Sarcoma Diseases 0.000 description 6
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 6
- 125000002947 alkylene group Chemical group 0.000 description 6
- 238000011717 athymic nude mouse Methods 0.000 description 6
- 230000018486 cell cycle phase Effects 0.000 description 6
- 230000000973 chemotherapeutic effect Effects 0.000 description 6
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 6
- 125000002883 imidazolyl group Chemical group 0.000 description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
- 230000026731 phosphorylation Effects 0.000 description 6
- 238000006366 phosphorylation reaction Methods 0.000 description 6
- 230000003389 potentiating effect Effects 0.000 description 6
- 108090000765 processed proteins & peptides Proteins 0.000 description 6
- 235000018102 proteins Nutrition 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 125000004434 sulfur atom Chemical group 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 150000003672 ureas Chemical class 0.000 description 6
- 201000005112 urinary bladder cancer Diseases 0.000 description 6
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 5
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 5
- 206010009944 Colon cancer Diseases 0.000 description 5
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 206010041067 Small cell lung cancer Diseases 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 5
- 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 5
- 150000002148 esters Chemical class 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 201000005202 lung cancer Diseases 0.000 description 5
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 5
- CPRRHERYRRXBRZ-SRVKXCTJSA-N methyl n-[(2s)-1-[[(2s)-1-hydroxy-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CO)C[C@@H]1CCNC1=O CPRRHERYRRXBRZ-SRVKXCTJSA-N 0.000 description 5
- 201000002528 pancreatic cancer Diseases 0.000 description 5
- 208000008443 pancreatic carcinoma Diseases 0.000 description 5
- 125000003386 piperidinyl group Chemical group 0.000 description 5
- 208000000587 small cell lung carcinoma Diseases 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 4
- 206010005949 Bone cancer Diseases 0.000 description 4
- 208000018084 Bone neoplasm Diseases 0.000 description 4
- 101100294115 Caenorhabditis elegans nhr-4 gene Proteins 0.000 description 4
- 206010008342 Cervix carcinoma Diseases 0.000 description 4
- 239000012623 DNA damaging agent Substances 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 4
- 230000010190 G1 phase Effects 0.000 description 4
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 4
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 4
- 102000001253 Protein Kinase Human genes 0.000 description 4
- 102000003923 Protein Kinase C Human genes 0.000 description 4
- 108090000315 Protein Kinase C Proteins 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 4
- 150000001449 anionic compounds Chemical class 0.000 description 4
- 230000001028 anti-proliverative effect Effects 0.000 description 4
- 230000000692 anti-sense effect Effects 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 4
- NOFOAYPPHIUXJR-APNQCZIXSA-N aphidicolin Chemical compound C1[C@@]23[C@@]4(C)CC[C@@H](O)[C@@](C)(CO)[C@@H]4CC[C@H]3C[C@H]1[C@](CO)(O)CC2 NOFOAYPPHIUXJR-APNQCZIXSA-N 0.000 description 4
- SEKZNWAQALMJNH-YZUCACDQSA-N aphidicolin Natural products C[C@]1(CO)CC[C@]23C[C@H]1C[C@@H]2CC[C@H]4[C@](C)(CO)[C@H](O)CC[C@]34C SEKZNWAQALMJNH-YZUCACDQSA-N 0.000 description 4
- 230000006907 apoptotic process Effects 0.000 description 4
- 125000004659 aryl alkyl thio group Chemical group 0.000 description 4
- 125000005110 aryl thio group Chemical group 0.000 description 4
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 4
- 235000013877 carbamide Nutrition 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 201000010881 cervical cancer Diseases 0.000 description 4
- 210000000349 chromosome Anatomy 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 201000004101 esophageal cancer Diseases 0.000 description 4
- 125000004475 heteroaralkyl group Chemical group 0.000 description 4
- 125000005114 heteroarylalkoxy group Chemical group 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 229910001412 inorganic anion Inorganic materials 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 208000032839 leukemia Diseases 0.000 description 4
- 125000006578 monocyclic heterocycloalkyl group Chemical group 0.000 description 4
- 150000002891 organic anions Chemical class 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 229920001184 polypeptide Polymers 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 4
- 108060006633 protein kinase Proteins 0.000 description 4
- 125000005554 pyridyloxy group Chemical group 0.000 description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 4
- 125000000168 pyrrolyl group Chemical group 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 108020004021 3-ketosteroid receptors Chemical group 0.000 description 3
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 3
- 102000014914 Carrier Proteins Human genes 0.000 description 3
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 3
- 102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 description 3
- 108010049894 Cyclic AMP-Dependent Protein Kinases Proteins 0.000 description 3
- 230000006820 DNA synthesis Effects 0.000 description 3
- 206010014733 Endometrial cancer Diseases 0.000 description 3
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 3
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 3
- 208000012766 Growth delay Diseases 0.000 description 3
- 208000008839 Kidney Neoplasms Diseases 0.000 description 3
- KYRVNWMVYQXFEU-UHFFFAOYSA-N Nocodazole Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1C(=O)C1=CC=CS1 KYRVNWMVYQXFEU-UHFFFAOYSA-N 0.000 description 3
- 229930012538 Paclitaxel Natural products 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 101100212791 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) YBL068W-A gene Proteins 0.000 description 3
- 206010057644 Testis cancer Diseases 0.000 description 3
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 3
- 101710086977 Tyrosine-protein kinase transforming protein Src Proteins 0.000 description 3
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 3
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 3
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 125000005129 aryl carbonyl group Chemical group 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 108091008324 binding proteins Proteins 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- YAYRGNWWLMLWJE-UHFFFAOYSA-L carboplatin Chemical compound O=C1O[Pt](N)(N)OC(=O)C11CCC1 YAYRGNWWLMLWJE-UHFFFAOYSA-L 0.000 description 3
- 230000006369 cell cycle progression Effects 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 3
- 230000001276 controlling effect Effects 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 125000005054 dihydropyrrolyl group Chemical group [H]C1=C([H])C([H])([H])C([H])([H])N1* 0.000 description 3
- 238000003182 dose-response assay Methods 0.000 description 3
- 229960000390 fludarabine Drugs 0.000 description 3
- 201000003444 follicular lymphoma Diseases 0.000 description 3
- 125000002541 furyl group Chemical group 0.000 description 3
- 210000003128 head Anatomy 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 230000036210 malignancy Effects 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 230000001394 metastastic effect Effects 0.000 description 3
- 229950006344 nocodazole Drugs 0.000 description 3
- 210000004940 nucleus Anatomy 0.000 description 3
- 125000004043 oxo group Chemical group O=* 0.000 description 3
- 229960001592 paclitaxel Drugs 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- WBXPDJSOTKVWSJ-ZDUSSCGKSA-L pemetrexed(2-) Chemical compound C=1NC=2NC(N)=NC(=O)C=2C=1CCC1=CC=C(C(=O)N[C@@H](CCC([O-])=O)C([O-])=O)C=C1 WBXPDJSOTKVWSJ-ZDUSSCGKSA-L 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 125000002755 pyrazolinyl group Chemical group 0.000 description 3
- 125000003226 pyrazolyl group Chemical group 0.000 description 3
- 230000008439 repair process Effects 0.000 description 3
- 230000001235 sensitizing effect Effects 0.000 description 3
- 235000004400 serine Nutrition 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 210000001082 somatic cell Anatomy 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 3
- 201000003120 testicular cancer Diseases 0.000 description 3
- 125000001544 thienyl group Chemical group 0.000 description 3
- 125000004001 thioalkyl group Chemical group 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 2
- BGFHMYJZJZLMHW-UHFFFAOYSA-N 4-[2-[[2-(1-benzothiophen-3-yl)-9-propan-2-ylpurin-6-yl]amino]ethyl]phenol Chemical compound N1=C(C=2C3=CC=CC=C3SC=2)N=C2N(C(C)C)C=NC2=C1NCCC1=CC=C(O)C=C1 BGFHMYJZJZLMHW-UHFFFAOYSA-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
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
- 206010004146 Basal cell carcinoma Diseases 0.000 description 2
- 102000001893 Bone Morphogenetic Protein Receptors Human genes 0.000 description 2
- 108010040422 Bone Morphogenetic Protein Receptors Proteins 0.000 description 2
- 206010007279 Carcinoid tumour of the gastrointestinal tract Diseases 0.000 description 2
- 208000010833 Chronic myeloid leukaemia 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
- 101100440695 Dictyostelium discoideum corB gene Proteins 0.000 description 2
- 230000004668 G2/M phase Effects 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 2
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 2
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 2
- 102000009465 Growth Factor Receptors Human genes 0.000 description 2
- 108010009202 Growth Factor Receptors Proteins 0.000 description 2
- 102100033636 Histone H3.2 Human genes 0.000 description 2
- 108010033040 Histones Proteins 0.000 description 2
- 206010021042 Hypopharyngeal cancer Diseases 0.000 description 2
- 206010056305 Hypopharyngeal neoplasm Diseases 0.000 description 2
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 description 2
- 102100020873 Interleukin-2 Human genes 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 2
- 206010023825 Laryngeal cancer Diseases 0.000 description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
- 240000007472 Leucaena leucocephala Species 0.000 description 2
- 208000032271 Malignant tumor of penis Diseases 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 101100365732 Mus musculus Sharpin gene Proteins 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
- 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 description 2
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 2
- 208000034176 Neoplasms, Germ Cell and Embryonal Diseases 0.000 description 2
- 206010031096 Oropharyngeal cancer Diseases 0.000 description 2
- 206010057444 Oropharyngeal neoplasm Diseases 0.000 description 2
- 206010034299 Penile cancer Diseases 0.000 description 2
- 108010082093 Placenta Growth Factor Proteins 0.000 description 2
- 102100035194 Placenta growth factor Human genes 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 101500026845 Rattus norvegicus C3-beta-c Proteins 0.000 description 2
- 206010038389 Renal cancer Diseases 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 208000004337 Salivary Gland Neoplasms Diseases 0.000 description 2
- 206010061934 Salivary gland cancer Diseases 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 208000000453 Skin Neoplasms Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102100040247 Tumor necrosis factor Human genes 0.000 description 2
- 208000006593 Urologic Neoplasms Diseases 0.000 description 2
- 206010047642 Vitiligo Diseases 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 208000009956 adenocarcinoma Diseases 0.000 description 2
- 230000001919 adrenal effect Effects 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- 125000004686 alkyl sulfanyl alkyl group Chemical group 0.000 description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 2
- 125000006319 alkynyl amino group Chemical group 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 229940045687 antimetabolites folic acid analogs Drugs 0.000 description 2
- 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 2
- 239000008135 aqueous vehicle Substances 0.000 description 2
- 125000005015 aryl alkynyl group Chemical group 0.000 description 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 2
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 2
- 229960001948 caffeine Drugs 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 201000002797 childhood leukemia Diseases 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000001886 ciliary effect Effects 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 230000001054 cortical effect Effects 0.000 description 2
- 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 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 230000021953 cytokinesis Effects 0.000 description 2
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 229960005304 fludarabine phosphate Drugs 0.000 description 2
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 2
- 229960002074 flutamide Drugs 0.000 description 2
- 201000010175 gallbladder cancer Diseases 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 208000003884 gestational trophoblastic disease Diseases 0.000 description 2
- 230000000762 glandular Effects 0.000 description 2
- 208000005017 glioblastoma Diseases 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 201000010536 head and neck cancer Diseases 0.000 description 2
- 208000014829 head and neck neoplasm Diseases 0.000 description 2
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 2
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 description 2
- PIPZGJSEDRMUAW-VJDCAHTMSA-N hydron;methyl (1s,15r,18s,19r,20s)-18-hydroxy-1,3,11,12,14,15,16,17,18,19,20,21-dodecahydroyohimban-19-carboxylate;chloride Chemical compound Cl.C1=CC=C2C(CCN3C[C@@H]4CC[C@H](O)[C@@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 PIPZGJSEDRMUAW-VJDCAHTMSA-N 0.000 description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
- 201000006866 hypopharynx cancer Diseases 0.000 description 2
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 150000002473 indoazoles Chemical class 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 230000016507 interphase Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000001786 isothiazolyl group Chemical group 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- 201000010982 kidney cancer Diseases 0.000 description 2
- 206010023841 laryngeal neoplasm Diseases 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 210000005265 lung cell Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 208000006178 malignant mesothelioma Diseases 0.000 description 2
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 2
- 230000033607 mismatch repair Effects 0.000 description 2
- 230000006618 mitotic catastrophe Effects 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 125000002757 morpholinyl group Chemical group 0.000 description 2
- 201000005962 mycosis fungoides Diseases 0.000 description 2
- 208000025113 myeloid leukemia Diseases 0.000 description 2
- 229940053128 nerve growth factor Drugs 0.000 description 2
- 210000004498 neuroglial cell Anatomy 0.000 description 2
- 239000002687 nonaqueous vehicle Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 238000011580 nude mouse model Methods 0.000 description 2
- 201000005443 oral cavity cancer Diseases 0.000 description 2
- 201000006958 oropharynx cancer Diseases 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 125000004095 oxindolyl group Chemical class N1(C(CC2=CC=CC=C12)=O)* 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- ZCCUUQDIBDJBTK-UHFFFAOYSA-N psoralen Chemical compound C1=C2OC(=O)C=CC2=CC2=C1OC=C2 ZCCUUQDIBDJBTK-UHFFFAOYSA-N 0.000 description 2
- 125000002098 pyridazinyl group Chemical group 0.000 description 2
- QNMMYUBZGLXCCK-UHFFFAOYSA-N pyrrolo[3,2-a]carbazole Chemical class N1=C2C=CC=CC2=C2C1=C1C=CN=C1C=C2 QNMMYUBZGLXCCK-UHFFFAOYSA-N 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 125000004962 sulfoxyl group Chemical group 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 229960004964 temozolomide Drugs 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 description 2
- 125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 125000004014 thioethyl group Chemical group [H]SC([H])([H])C([H])([H])* 0.000 description 2
- 125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 description 2
- YOJJQORBOZKLCC-UHFFFAOYSA-N thiophen-2-ylurea Chemical class NC(=O)NC1=CC=CS1 YOJJQORBOZKLCC-UHFFFAOYSA-N 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 150000003918 triazines Chemical class 0.000 description 2
- 125000001425 triazolyl group Chemical group 0.000 description 2
- 102000003390 tumor necrosis factor Human genes 0.000 description 2
- 210000003741 urothelium Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 229940090523 yocon Drugs 0.000 description 2
- MWWSFMDVAYGXBV-MYPASOLCSA-N (7r,9s)-7-[(2r,4s,5s,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione;hydrochloride Chemical compound Cl.O([C@@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 MWWSFMDVAYGXBV-MYPASOLCSA-N 0.000 description 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- ZNGWEEUXTBNKFR-UHFFFAOYSA-N 1,4-oxazepane Chemical group C1CNCCOC1 ZNGWEEUXTBNKFR-UHFFFAOYSA-N 0.000 description 1
- WVWOOAYQYLJEFD-UHFFFAOYSA-N 1-(2-nitroimidazol-1-yl)-3-piperidin-1-ylpropan-2-ol Chemical compound C1=CN=C([N+]([O-])=O)N1CC(O)CN1CCCCC1 WVWOOAYQYLJEFD-UHFFFAOYSA-N 0.000 description 1
- GQRKMLLQHILOIC-UHFFFAOYSA-N 1-(5-methylpyrazin-2-yl)-3-(5-methyl-2-pyridin-4-ylphenyl)urea Chemical compound C=1C(C)=CC=C(C=2C=CN=CC=2)C=1NC(=O)NC1=CN=C(C)C=N1 GQRKMLLQHILOIC-UHFFFAOYSA-N 0.000 description 1
- RSEOJQCKHFLXJN-UHFFFAOYSA-N 1-(5-methylpyrazin-2-yl)-3-[2-(1,3-oxazol-5-yl)phenyl]urea Chemical compound C1=NC(C)=CN=C1NC(=O)NC1=CC=CC=C1C1=CN=CO1 RSEOJQCKHFLXJN-UHFFFAOYSA-N 0.000 description 1
- FRSARNVNUBVFOF-UHFFFAOYSA-N 1-(5-methylpyrazin-2-yl)-3-[2-(piperidin-3-ylmethoxy)-5-(trifluoromethyl)phenyl]urea Chemical compound C1=NC(C)=CN=C1NC(=O)NC1=CC(C(F)(F)F)=CC=C1OCC1CNCCC1 FRSARNVNUBVFOF-UHFFFAOYSA-N 0.000 description 1
- FRSARNVNUBVFOF-CYBMUJFWSA-N 1-(5-methylpyrazin-2-yl)-3-[2-[[(3r)-piperidin-3-yl]methoxy]-5-(trifluoromethyl)phenyl]urea Chemical compound C1=NC(C)=CN=C1NC(=O)NC1=CC(C(F)(F)F)=CC=C1OC[C@H]1CNCCC1 FRSARNVNUBVFOF-CYBMUJFWSA-N 0.000 description 1
- CYZXIWXYLNFXIK-UHFFFAOYSA-N 1-(5-methylpyrazin-2-yl)-3-[5-methyl-2-(1,3-thiazol-2-yl)phenyl]urea Chemical compound C=1N=C(C)C=NC=1NC(=O)NC1=CC(C)=CC=C1C1=NC=CS1 CYZXIWXYLNFXIK-UHFFFAOYSA-N 0.000 description 1
- LKESKNJFVVDSHK-UHFFFAOYSA-N 1-(5-methylpyrazin-2-yl)-3-[6-(pyridin-3-ylmethoxy)-2,3-dihydro-1,4-benzodioxin-7-yl]urea Chemical compound C1=NC(C)=CN=C1NC(=O)NC(C(=C1)OCC=2C=NC=CC=2)=CC2=C1OCCO2 LKESKNJFVVDSHK-UHFFFAOYSA-N 0.000 description 1
- QAJYMZQFMATQET-UHFFFAOYSA-N 1-[2-[(1-methylpiperidin-3-yl)methoxy]-5-(trifluoromethyl)phenyl]-3-(5-methylpyrazin-2-yl)urea Chemical compound C1N(C)CCCC1COC1=CC=C(C(F)(F)F)C=C1NC(=O)NC1=CN=C(C)C=N1 QAJYMZQFMATQET-UHFFFAOYSA-N 0.000 description 1
- WKROLWQBCSBACM-UHFFFAOYSA-N 1-[2-[2-(dimethylamino)ethoxy]-5-ethynylphenyl]-3-(5-methylpyrazin-2-yl)urea Chemical compound CN(C)CCOC1=CC=C(C#C)C=C1NC(=O)NC1=CN=C(C)C=N1 WKROLWQBCSBACM-UHFFFAOYSA-N 0.000 description 1
- DOZZICCLCZDDIE-UHFFFAOYSA-N 1-[3-[(1-methylpiperidin-2-yl)methoxy]-5,6,7,8-tetrahydronaphthalen-2-yl]-3-(5-methylpyrazin-2-yl)urea Chemical compound CN1CCCCC1COC(C(=C1)NC(=O)NC=2N=CC(C)=NC=2)=CC2=C1CCCC2 DOZZICCLCZDDIE-UHFFFAOYSA-N 0.000 description 1
- GPPZRLJLJPCNKJ-UHFFFAOYSA-N 1-[3-[(1-methylpiperidin-3-yl)methoxy]-5,6,7,8-tetrahydronaphthalen-2-yl]-3-(5-methylpyrazin-2-yl)urea Chemical compound C1N(C)CCCC1COC(C(=C1)NC(=O)NC=2N=CC(C)=NC=2)=CC2=C1CCCC2 GPPZRLJLJPCNKJ-UHFFFAOYSA-N 0.000 description 1
- HEGDOJYWJMGDEG-UHFFFAOYSA-N 1-[3-[2-(dimethylamino)ethoxy]-5,6,7,8-tetrahydronaphthalen-2-yl]-3-(5-methylpyrazin-2-yl)urea Chemical compound CN(C)CCOC1=CC=2CCCCC=2C=C1NC(=O)NC1=CN=C(C)C=N1 HEGDOJYWJMGDEG-UHFFFAOYSA-N 0.000 description 1
- VGUKGDBJYNQRGW-UHFFFAOYSA-N 1-[6-[2-(dimethylamino)ethoxy]-2,3-dihydro-1,4-benzodioxin-7-yl]-3-(5-methylpyrazin-2-yl)urea Chemical compound CN(C)CCOC1=CC=2OCCOC=2C=C1NC(=O)NC1=CN=C(C)C=N1 VGUKGDBJYNQRGW-UHFFFAOYSA-N 0.000 description 1
- 102100025573 1-alkyl-2-acetylglycerophosphocholine esterase Human genes 0.000 description 1
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- DBPWSSGDRRHUNT-CEGNMAFCSA-N 17α-hydroxyprogesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)C)(O)[C@@]1(C)CC2 DBPWSSGDRRHUNT-CEGNMAFCSA-N 0.000 description 1
- ZWOMUDQWODQGQH-UHFFFAOYSA-N 1H-pyrrolo[2,3-g][1,2]benzodiazepin-2-one Chemical class C1=CC2=NN=CC=CC2=C2C1=CC(=O)N2 ZWOMUDQWODQGQH-UHFFFAOYSA-N 0.000 description 1
- GBTVCCZNQCRKBW-UHFFFAOYSA-N 1h-benzimidazole;1h-quinolin-2-one Chemical class C1=CC=C2NC=NC2=C1.C1=CC=C2NC(=O)C=CC2=C1 GBTVCCZNQCRKBW-UHFFFAOYSA-N 0.000 description 1
- BATGRBMPRGJUMM-UHFFFAOYSA-N 2-amino-3,7-dihydropurine-6-thione;pyridine-3-carboxamide Chemical compound NC(=O)C1=CC=CN=C1.N1C(N)=NC(=S)C2=C1N=CN2 BATGRBMPRGJUMM-UHFFFAOYSA-N 0.000 description 1
- MWBWWFOAEOYUST-UHFFFAOYSA-N 2-aminopurine Chemical compound NC1=NC=C2N=CNC2=N1 MWBWWFOAEOYUST-UHFFFAOYSA-N 0.000 description 1
- MHIITNFQDPFSES-UHFFFAOYSA-N 25,26,27,28-tetrazahexacyclo[16.6.1.13,6.18,11.113,16.019,24]octacosa-1(25),2,4,6,8(27),9,11,13,15,17,19,21,23-tridecaene Chemical class N1C(C=C2C3=CC=CC=C3C(C=C3NC(=C4)C=C3)=N2)=CC=C1C=C1C=CC4=N1 MHIITNFQDPFSES-UHFFFAOYSA-N 0.000 description 1
- PFHVEIAPEQYYCX-UHFFFAOYSA-N 2h-[1]benzofuro[3,2-e]isoindole Chemical class O1C2=CC=CC=C2C2=C1C=CC1=CNC=C21 PFHVEIAPEQYYCX-UHFFFAOYSA-N 0.000 description 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 1
- JTKFRFMSUBOCIQ-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-1h-indazole Chemical class C1=CC=C2C(C=3NC4=CC=CC=C4N=3)=NNC2=C1 JTKFRFMSUBOCIQ-UHFFFAOYSA-N 0.000 description 1
- NUGLIYXAARVRPQ-UHFFFAOYSA-N 3-(2-nitroimidazol-1-yl)propane-1,2-diol Chemical compound OCC(O)CN1C=CN=C1[N+]([O-])=O NUGLIYXAARVRPQ-UHFFFAOYSA-N 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- VXGRJERITKFWPL-UHFFFAOYSA-N 4',5'-Dihydropsoralen Natural products C1=C2OC(=O)C=CC2=CC2=C1OCC2 VXGRJERITKFWPL-UHFFFAOYSA-N 0.000 description 1
- MJYFVDNMTKLGTH-UHFFFAOYSA-N 4-bromo-6-(3,4-dichlorophenyl)sulfanyl-1-[[4-(dimethylcarbamoyl)phenyl]methyl]indole-2-carboxylic acid Chemical compound BrC1=C2C=C(N(C2=CC(=C1)SC1=CC(=C(C=C1)Cl)Cl)CC1=CC=C(C=C1)C(N(C)C)=O)C(=O)O MJYFVDNMTKLGTH-UHFFFAOYSA-N 0.000 description 1
- 125000001054 5 membered carbocyclic group Chemical group 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- PBCZSGKMGDDXIJ-XMCQDBRXSA-N 7-hydroxystaurosporine Chemical compound N([C@@H](O)C1=C2C3=CC=CC=C3N3C2=C24)C(=O)C1=C2C1=CC=CC=C1N4[C@@H]1C[C@@H](NC)[C@@H](OC)[C@@]3(C)O1 PBCZSGKMGDDXIJ-XMCQDBRXSA-N 0.000 description 1
- PFWLFWPASULGAN-UHFFFAOYSA-N 7-methylxanthine Chemical compound N1C(=O)NC(=O)C2=C1N=CN2C PFWLFWPASULGAN-UHFFFAOYSA-N 0.000 description 1
- PBCZSGKMGDDXIJ-UHFFFAOYSA-N 7beta-hydroxystaurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3C(O)NC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 PBCZSGKMGDDXIJ-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- RTAPDZBZLSXHQQ-UHFFFAOYSA-N 8-methyl-3,7-dihydropurine-2,6-dione Chemical class N1C(=O)NC(=O)C2=C1N=C(C)N2 RTAPDZBZLSXHQQ-UHFFFAOYSA-N 0.000 description 1
- 206010000830 Acute leukaemia Diseases 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- 206010061424 Anal cancer Diseases 0.000 description 1
- 208000000058 Anaplasia Diseases 0.000 description 1
- 102100022987 Angiogenin Human genes 0.000 description 1
- 102000009840 Angiopoietins Human genes 0.000 description 1
- 108010009906 Angiopoietins Proteins 0.000 description 1
- 208000007860 Anus Neoplasms Diseases 0.000 description 1
- 101100244083 Arabidopsis thaliana PKL gene Proteins 0.000 description 1
- 101100515517 Arabidopsis thaliana XI-I gene Proteins 0.000 description 1
- 108010024976 Asparaginase Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 0.000 description 1
- 108010070075 Bacteriochlorophyll A Proteins 0.000 description 1
- 108010081589 Becaplermin Proteins 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 206010004593 Bile duct cancer Diseases 0.000 description 1
- 108010049931 Bone Morphogenetic Protein 2 Proteins 0.000 description 1
- 108010049951 Bone Morphogenetic Protein 3 Proteins 0.000 description 1
- 108010049955 Bone Morphogenetic Protein 4 Proteins 0.000 description 1
- 108010049974 Bone Morphogenetic Protein 6 Proteins 0.000 description 1
- 108010049870 Bone Morphogenetic Protein 7 Proteins 0.000 description 1
- 102100028726 Bone morphogenetic protein 10 Human genes 0.000 description 1
- 101710118482 Bone morphogenetic protein 10 Proteins 0.000 description 1
- 102000003928 Bone morphogenetic protein 15 Human genes 0.000 description 1
- 108090000349 Bone morphogenetic protein 15 Proteins 0.000 description 1
- 102100024506 Bone morphogenetic protein 2 Human genes 0.000 description 1
- 102100024504 Bone morphogenetic protein 3 Human genes 0.000 description 1
- 102100024505 Bone morphogenetic protein 4 Human genes 0.000 description 1
- 102100022525 Bone morphogenetic protein 6 Human genes 0.000 description 1
- 102100022544 Bone morphogenetic protein 7 Human genes 0.000 description 1
- 102100022545 Bone morphogenetic protein 8B Human genes 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 1
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 1
- 208000011691 Burkitt lymphomas Diseases 0.000 description 1
- 102100024167 C-C chemokine receptor type 3 Human genes 0.000 description 1
- 101710149862 C-C chemokine receptor type 3 Proteins 0.000 description 1
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 description 1
- 101150106671 COMT gene Proteins 0.000 description 1
- 101100220616 Caenorhabditis elegans chk-2 gene Proteins 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 102000006459 Checkpoint Kinase 1 Human genes 0.000 description 1
- 108010019244 Checkpoint Kinase 1 Proteins 0.000 description 1
- 108010008951 Chemokine CXCL12 Proteins 0.000 description 1
- JWBOIMRXGHLCPP-UHFFFAOYSA-N Chloditan Chemical compound C=1C=CC=C(Cl)C=1C(C(Cl)Cl)C1=CC=C(Cl)C=C1 JWBOIMRXGHLCPP-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 102000002427 Cyclin B Human genes 0.000 description 1
- 108010068150 Cyclin B Proteins 0.000 description 1
- 102100036873 Cyclin-I Human genes 0.000 description 1
- 102100021906 Cyclin-O Human genes 0.000 description 1
- 102100025621 Cytochrome b-245 heavy chain Human genes 0.000 description 1
- 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 1
- 230000004543 DNA replication Effects 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 101100502742 Danio rerio fgf8a gene Proteins 0.000 description 1
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 102000002266 Dual-Specificity Phosphatases Human genes 0.000 description 1
- 108010000518 Dual-Specificity Phosphatases Proteins 0.000 description 1
- 102400000686 Endothelin-1 Human genes 0.000 description 1
- 101800004490 Endothelin-1 Proteins 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 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 description 1
- 101150092822 FGF5 gene Proteins 0.000 description 1
- 101150095289 FGF7 gene Proteins 0.000 description 1
- 101150112093 FGF9 gene Proteins 0.000 description 1
- WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical class F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 description 1
- 201000001342 Fallopian tube cancer Diseases 0.000 description 1
- 208000013452 Fallopian tube neoplasm Diseases 0.000 description 1
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 1
- 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 1
- 108090000385 Fibroblast growth factor 7 Proteins 0.000 description 1
- 102000003972 Fibroblast growth factor 7 Human genes 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 230000037057 G1 phase arrest Effects 0.000 description 1
- 230000037060 G2 phase arrest Effects 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 201000010915 Glioblastoma multiforme Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000006771 Gonadotropins Human genes 0.000 description 1
- 108010086677 Gonadotropins Proteins 0.000 description 1
- 108010090290 Growth Differentiation Factor 2 Proteins 0.000 description 1
- 102100040898 Growth/differentiation factor 11 Human genes 0.000 description 1
- 101710194452 Growth/differentiation factor 11 Proteins 0.000 description 1
- 102100040892 Growth/differentiation factor 2 Human genes 0.000 description 1
- 102100035379 Growth/differentiation factor 5 Human genes 0.000 description 1
- 101710204282 Growth/differentiation factor 5 Proteins 0.000 description 1
- 102100035368 Growth/differentiation factor 6 Human genes 0.000 description 1
- 101710204281 Growth/differentiation factor 6 Proteins 0.000 description 1
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 1
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000899368 Homo sapiens Bone morphogenetic protein 8B Proteins 0.000 description 1
- 101000713124 Homo sapiens Cyclin-I Proteins 0.000 description 1
- 101000897441 Homo sapiens Cyclin-O Proteins 0.000 description 1
- 101000871708 Homo sapiens Proheparin-binding EGF-like growth factor Proteins 0.000 description 1
- 208000006937 Hydatidiform mole Diseases 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 101000668058 Infectious salmon anemia virus (isolate Atlantic salmon/Norway/810/9/99) RNA-directed RNA polymerase catalytic subunit Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 1
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 1
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 1
- 102100040019 Interferon alpha-1/13 Human genes 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102100030694 Interleukin-11 Human genes 0.000 description 1
- 108050003558 Interleukin-17 Proteins 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- 108010002335 Interleukin-9 Proteins 0.000 description 1
- 208000005125 Invasive Hydatidiform Mole Diseases 0.000 description 1
- 208000028257 Joubert syndrome with oculorenal defect Diseases 0.000 description 1
- WZNJWVWKTVETCG-YFKPBYRVSA-N L-mimosine Chemical compound OC(=O)[C@@H](N)CN1C=CC(=O)C(O)=C1 WZNJWVWKTVETCG-YFKPBYRVSA-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
- 208000035561 Leukaemic infiltration brain Diseases 0.000 description 1
- 108090000581 Leukemia inhibitory factor Proteins 0.000 description 1
- 102000004058 Leukemia inhibitory factor Human genes 0.000 description 1
- 108010000817 Leuprolide Proteins 0.000 description 1
- 208000028018 Lymphocytic leukaemia Diseases 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- 101150024075 Mapk1 gene Proteins 0.000 description 1
- 208000015021 Meningeal Neoplasms Diseases 0.000 description 1
- 206010027480 Metastatic malignant melanoma Diseases 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- 229920000715 Mucilage Polymers 0.000 description 1
- 101100490437 Mus musculus Acvrl1 gene Proteins 0.000 description 1
- 101100446521 Mus musculus Fgf6 gene Proteins 0.000 description 1
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 description 1
- TWBVKLQCVIRJQU-UHFFFAOYSA-N N-(1H-pyrrolo[3,2-b]pyridin-2-yl)formamide Chemical class C1=CC=C2NC(NC=O)=CC2=N1 TWBVKLQCVIRJQU-UHFFFAOYSA-N 0.000 description 1
- 206010028729 Nasal cavity cancer Diseases 0.000 description 1
- 206010029098 Neoplasm skin Diseases 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 102000015336 Nerve Growth Factor Human genes 0.000 description 1
- 108090000742 Neurotrophin 3 Proteins 0.000 description 1
- 102100029268 Neurotrophin-3 Human genes 0.000 description 1
- 102000003683 Neurotrophin-4 Human genes 0.000 description 1
- 108090000099 Neurotrophin-4 Proteins 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 108010064527 OSM-LIF Receptors Proteins 0.000 description 1
- 102000015278 OSM-LIF Receptors Human genes 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 108091008606 PDGF receptors Proteins 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 1
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 1
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 1
- 102100040990 Platelet-derived growth factor subunit B Human genes 0.000 description 1
- 101710103494 Platelet-derived growth factor subunit B Proteins 0.000 description 1
- 206010035603 Pleural mesothelioma Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 208000026149 Primary peritoneal carcinoma Diseases 0.000 description 1
- 102100033762 Proheparin-binding EGF-like growth factor Human genes 0.000 description 1
- 108091008611 Protein Kinase B Proteins 0.000 description 1
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 102000005765 Proto-Oncogene Proteins c-akt Human genes 0.000 description 1
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 1
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 1
- 108010089836 Proto-Oncogene Proteins c-met Proteins 0.000 description 1
- 102000008022 Proto-Oncogene Proteins c-met Human genes 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 101500026849 Rattus norvegicus C3a anaphylatoxin Proteins 0.000 description 1
- 108050002653 Retinoblastoma protein Proteins 0.000 description 1
- CGZKSPLDUIRCIO-UHFFFAOYSA-N Scytonemin Natural products OC1=CC=C(C=C1)C=C1C(C(=C2C1=NC=1C=CC=CC2=1)C=1C(C(C2=NC=3C=CC=CC=3C2=1)=CC1=CC=C(C=C1)O)=O)=O CGZKSPLDUIRCIO-UHFFFAOYSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 208000021712 Soft tissue sarcoma Diseases 0.000 description 1
- 108010017622 Somatomedin Receptors Proteins 0.000 description 1
- 102000004584 Somatomedin Receptors Human genes 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 102100021669 Stromal cell-derived factor 1 Human genes 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- PDMMFKSKQVNJMI-BLQWBTBKSA-N Testosterone propionate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CC)[C@@]1(C)CC2 PDMMFKSKQVNJMI-BLQWBTBKSA-N 0.000 description 1
- 102000036693 Thrombopoietin Human genes 0.000 description 1
- 108010041111 Thrombopoietin Proteins 0.000 description 1
- 102100031372 Thymidine phosphorylase Human genes 0.000 description 1
- 108700023160 Thymidine phosphorylases Proteins 0.000 description 1
- 208000000728 Thymus Neoplasms Diseases 0.000 description 1
- 101710183280 Topoisomerase Proteins 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 102000004504 Urokinase Plasminogen Activator Receptors Human genes 0.000 description 1
- 108010042352 Urokinase Plasminogen Activator Receptors Proteins 0.000 description 1
- 206010047741 Vulval cancer Diseases 0.000 description 1
- 208000004354 Vulvar Neoplasms Diseases 0.000 description 1
- 208000008383 Wilms tumor Diseases 0.000 description 1
- 101000797997 Xenopus laevis RAC-alpha serine/threonine-protein kinase Proteins 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- UMSSUAVKDTVTDQ-UHFFFAOYSA-N [Sn].CCC(C1=CC=C(O)C=C1)=C(/C1=CC=C(O)C=C1)CC Chemical compound [Sn].CCC(C1=CC=C(O)C=C1)=C(/C1=CC=C(O)C=C1)CC UMSSUAVKDTVTDQ-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 201000005179 adrenal carcinoma Diseases 0.000 description 1
- 201000005188 adrenal gland cancer Diseases 0.000 description 1
- 230000001780 adrenocortical effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 125000005081 alkoxyalkoxyalkyl group Chemical group 0.000 description 1
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 description 1
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 1
- 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000005122 aminoalkylamino group Chemical group 0.000 description 1
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical group [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 229940030486 androgens Drugs 0.000 description 1
- 108010072788 angiogenin Proteins 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- RGHILYZRVFRRNK-UHFFFAOYSA-N anthracene-1,2-dione Chemical compound C1=CC=C2C=C(C(C(=O)C=C3)=O)C3=CC2=C1 RGHILYZRVFRRNK-UHFFFAOYSA-N 0.000 description 1
- 230000002280 anti-androgenic effect Effects 0.000 description 1
- 229940046836 anti-estrogen Drugs 0.000 description 1
- 230000001833 anti-estrogenic effect Effects 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
- 229940053202 antiepileptics carboxamide derivative Drugs 0.000 description 1
- 239000003080 antimitotic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 201000011165 anus cancer Diseases 0.000 description 1
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 125000005160 aryl oxy alkyl group Chemical group 0.000 description 1
- 239000005667 attractant Substances 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- DSJXIQQMORJERS-AGGZHOMASA-M bacteriochlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC([C@H](CC)[C@H]3C)=[N+]4C3=CC3=C(C(C)=O)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 DSJXIQQMORJERS-AGGZHOMASA-M 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 208000026900 bile duct neoplasm Diseases 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000001851 biosynthetic effect Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 1
- 229950004398 broxuridine Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 101150073031 cdk2 gene Proteins 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 230000031902 chemoattractant activity Effects 0.000 description 1
- 208000006990 cholangiocarcinoma Diseases 0.000 description 1
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical compound C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 1
- 125000003016 chromanyl group Chemical class O1C(CCC2=CC=CC=C12)* 0.000 description 1
- 208000016532 chronic granulomatous disease Diseases 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- POADTFBBIXOWFJ-VWLOTQADSA-N cositecan Chemical compound C1=CC=C2C(CC[Si](C)(C)C)=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 POADTFBBIXOWFJ-VWLOTQADSA-N 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 201000007241 cutaneous T cell lymphoma Diseases 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 238000004163 cytometry Methods 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000032459 dedifferentiation Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 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
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000004069 differentiation Effects 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
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 208000010932 epithelial neoplasm Diseases 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 210000003236 esophagogastric junction Anatomy 0.000 description 1
- 229960001842 estramustine Drugs 0.000 description 1
- FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 description 1
- 229960004750 estramustine phosphate Drugs 0.000 description 1
- ADFOJJHRTBFFOF-RBRWEJTLSA-N estramustine phosphate Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)OP(O)(O)=O)[C@@H]4[C@@H]3CCC2=C1 ADFOJJHRTBFFOF-RBRWEJTLSA-N 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- WCDWBPCFGJXFJZ-UHFFFAOYSA-N etanidazole Chemical compound OCCNC(=O)CN1C=CN=C1[N+]([O-])=O WCDWBPCFGJXFJZ-UHFFFAOYSA-N 0.000 description 1
- 229950006566 etanidazole Drugs 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 229960002568 ethinylestradiol Drugs 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 210000005002 female reproductive tract Anatomy 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 229930003944 flavone Natural products 0.000 description 1
- 150000002213 flavones Chemical class 0.000 description 1
- 235000011949 flavones Nutrition 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 208000010749 gastric carcinoma Diseases 0.000 description 1
- 201000007492 gastroesophageal junction adenocarcinoma Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 201000008822 gestational choriocarcinoma Diseases 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 239000002622 gonadotropin Substances 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 208000029824 high grade glioma Diseases 0.000 description 1
- 239000003668 hormone analog Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 125000004464 hydroxyphenyl group Chemical group 0.000 description 1
- 229960002899 hydroxyprogesterone Drugs 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 238000013388 immunohistochemistry analysis Methods 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940124589 immunosuppressive drug Drugs 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000012606 in vitro cell culture Methods 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- XSTBCICLDQSQIQ-UHFFFAOYSA-N indeno[2,1-c]pyrazole Chemical class C1=CC=C2C3=CN=NC3=CC2=C1 XSTBCICLDQSQIQ-UHFFFAOYSA-N 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 102000028416 insulin-like growth factor binding Human genes 0.000 description 1
- 108091022911 insulin-like growth factor binding Proteins 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- WZNJWVWKTVETCG-UHFFFAOYSA-N kojic acid Natural products OC(=O)C(N)CN1C=CC(=O)C(O)=C1 WZNJWVWKTVETCG-UHFFFAOYSA-N 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 1
- 229960004338 leuprorelin Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 150000002632 lipids Chemical group 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 208000026807 lung carcinoid tumor Diseases 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 208000003747 lymphoid leukemia Diseases 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 210000005001 male reproductive tract Anatomy 0.000 description 1
- 201000011614 malignant glioma Diseases 0.000 description 1
- 208000008585 mastocytosis Diseases 0.000 description 1
- 229960004616 medroxyprogesterone Drugs 0.000 description 1
- FRQMUZJSZHZSGN-HBNHAYAOSA-N medroxyprogesterone Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](O)(C(C)=O)CC[C@H]21 FRQMUZJSZHZSGN-HBNHAYAOSA-N 0.000 description 1
- 229960004296 megestrol acetate Drugs 0.000 description 1
- RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 208000011645 metastatic carcinoma Diseases 0.000 description 1
- 208000021039 metastatic melanoma Diseases 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical class CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 1
- 229960000282 metronidazole Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 229950002289 mimosine Drugs 0.000 description 1
- OBBCSXFCDPPXOL-UHFFFAOYSA-N misonidazole Chemical compound COCC(O)CN1C=CN=C1[N+]([O-])=O OBBCSXFCDPPXOL-UHFFFAOYSA-N 0.000 description 1
- 229950010514 misonidazole Drugs 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
- 229960000350 mitotane Drugs 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- 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 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 230000000921 morphogenic effect Effects 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 229940032018 neurotrophin 3 Drugs 0.000 description 1
- 229940097998 neurotrophin 4 Drugs 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- MDJFHRLTPRPZLY-UHFFFAOYSA-N nimorazole Chemical compound [O-][N+](=O)C1=CN=CN1CCN1CCOCC1 MDJFHRLTPRPZLY-UHFFFAOYSA-N 0.000 description 1
- 229960004918 nimorazole Drugs 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 201000002628 peritoneum cancer Diseases 0.000 description 1
- 230000003094 perturbing effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000865 phosphorylative effect Effects 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 229940109328 photofrin Drugs 0.000 description 1
- 229950010456 pimonidazole Drugs 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000011505 plaster Substances 0.000 description 1
- 108010000685 platelet-derived growth factor AB Proteins 0.000 description 1
- 229960003171 plicamycin Drugs 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 208000022131 polyp of large intestine Diseases 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- 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 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 230000009290 primary effect Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 208000023958 prostate neoplasm Diseases 0.000 description 1
- 230000009822 protein phosphorylation Effects 0.000 description 1
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- BSYFXFLGOGQHFU-UHFFFAOYSA-N pyrrolo[2,3-g][1,2]benzodiazepine Chemical class N1=NC=CC=C2C3=NC=CC3=CC=C21 BSYFXFLGOGQHFU-UHFFFAOYSA-N 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000022983 regulation of cell cycle Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000034408 response to ionizing radiation Effects 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- CGZKSPLDUIRCIO-RPCRKUJJSA-N scytonemin Chemical compound C1=CC(O)=CC=C1\C=C\1C2=NC3=CC=CC=C3C2=C(C=2C(C(=C/C=3C=CC(O)=CC=3)/C=3C=2C2=CC=CC=C2N=3)=O)C/1=O CGZKSPLDUIRCIO-RPCRKUJJSA-N 0.000 description 1
- 238000005204 segregation Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 150000003355 serines Chemical class 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000020374 simple syrup Nutrition 0.000 description 1
- 206010073373 small intestine adenocarcinoma Diseases 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical class C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 201000000498 stomach carcinoma Diseases 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000011521 systemic chemotherapy Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 229940063683 taxotere Drugs 0.000 description 1
- 229960001712 testosterone propionate Drugs 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 125000005000 thioaryl group Chemical group 0.000 description 1
- GLQWRXYOTXRDNH-UHFFFAOYSA-N thiophen-2-amine Chemical class NC1=CC=CS1 GLQWRXYOTXRDNH-UHFFFAOYSA-N 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 201000009377 thymus cancer Diseases 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- QVMPZNRFXAKISM-UHFFFAOYSA-N tirapazamine Chemical compound C1=CC=C2[N+]([O-])=NC(=N)N(O)C2=C1 QVMPZNRFXAKISM-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000816 toxic dose Toxicity 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 208000037965 uterine sarcoma Diseases 0.000 description 1
- 206010046885 vaginal cancer Diseases 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 201000005102 vulva cancer Diseases 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/15—Oximes (>C=N—O—); Hydrazines (>N—N<); Hydrazones (>N—N=) ; Imines (C—N=C)
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/243—Platinum; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/14—Peptides containing saccharide radicals; Derivatives thereof, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/12—Keratolytics, e.g. wart or anti-corn preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Inorganic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Urology & Nephrology (AREA)
- Gastroenterology & Hepatology (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Transplantation (AREA)
- Hematology (AREA)
- Ophthalmology & Optometry (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US50392503P | 2003-09-17 | 2003-09-17 | |
| US60/503,925 | 2003-09-17 | ||
| PCT/US2004/030806 WO2005027907A1 (en) | 2003-09-17 | 2004-09-17 | Use of chk1 inhibitors to control cell proliferation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2539320A1 true CA2539320A1 (en) | 2005-03-31 |
Family
ID=34375418
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002539320A Abandoned CA2539320A1 (en) | 2003-09-17 | 2004-09-17 | Use of chk1 inhibitors to control cell proliferation |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US20070185013A1 (https=) |
| EP (1) | EP1667684A1 (https=) |
| JP (1) | JP2007519609A (https=) |
| KR (1) | KR20070064414A (https=) |
| CN (1) | CN1882342A (https=) |
| AU (1) | AU2004274013A1 (https=) |
| CA (1) | CA2539320A1 (https=) |
| IL (1) | IL174334A0 (https=) |
| MX (1) | MXPA06003110A (https=) |
| NO (1) | NO20061475L (https=) |
| RU (1) | RU2006112548A (https=) |
| WO (1) | WO2005027907A1 (https=) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7196078B2 (en) | 2002-09-04 | 2007-03-27 | Schering Corpoartion | Trisubstituted and tetrasubstituted pyrazolopyrimidines as cyclin dependent kinase inhibitors |
| EP1694686A1 (en) | 2003-12-19 | 2006-08-30 | Takeda San Diego, Inc. | Kinase inhibitors |
| WO2005100999A2 (en) | 2004-04-08 | 2005-10-27 | Cornell Research Foundation, Inc. | Functional immunohistochemical cell cycle analysis as a prognostic indicator for cancer |
| WO2006023931A2 (en) | 2004-08-18 | 2006-03-02 | Takeda San Diego, Inc. | Kinase inhibitors |
| EP1778648A2 (en) * | 2004-08-19 | 2007-05-02 | ICOS Corporation | Compounds useful for inhibiting chk1 |
| EP1812439B2 (en) | 2004-10-15 | 2017-12-06 | Takeda Pharmaceutical Company Limited | Kinase inhibitors |
| MX2007010073A (es) * | 2005-02-18 | 2007-10-10 | Astrazeneca Ab | Metodo para determinar la respuesta de los inhibidores de chk1. |
| US8119655B2 (en) | 2005-10-07 | 2012-02-21 | Takeda Pharmaceutical Company Limited | Kinase inhibitors |
| WO2007080124A1 (en) * | 2006-01-12 | 2007-07-19 | Novartis Ag | Combination of mtor inhibitor and antipolate compound |
| SG158147A1 (en) | 2006-10-09 | 2010-01-29 | Takeda Pharmaceutical | Kinase inhibitors |
| WO2008067027A2 (en) * | 2006-10-20 | 2008-06-05 | Icos Corporation | Compositions of chkl inhibitors and cyclodextrin |
| JP2010510222A (ja) * | 2006-11-17 | 2010-04-02 | シェーリング コーポレイション | 増殖性障害に対する併用療法 |
| GB2453011B (en) * | 2006-12-29 | 2010-06-23 | Tracon Pharmaceuticals Inc | Antifolate agent compositions in the treatment of cancer |
| US9000027B2 (en) * | 2008-02-04 | 2015-04-07 | Dana-Farber Cancer Institute, Inc. | Chk1 suppresses a caspase-2 apoptotic response to DNA damage that bypasses p53, bcl-2 and caspase-3 |
| US20100331265A1 (en) * | 2009-03-20 | 2010-12-30 | Tompkins Ronald G | Methods for the prevention and treatment of burn injuries and secondary complications |
| JP5805071B2 (ja) * | 2009-04-11 | 2015-11-04 | アレイ バイオファーマ、インコーポレイテッド | Dna損傷因子増強のためのチェックポイントキナーゼ1阻害剤 |
| US8481557B2 (en) | 2009-04-11 | 2013-07-09 | Array Biopharma Inc. | Method of treatment using checkpoint kinase 1 inhibitors |
| RU2017127088A (ru) * | 2010-11-16 | 2019-02-04 | Эррэй Биофарма Инк. | Комбинация ингибиторов чекпойнт-киназы 1 и ингибиторов киназы wee 1 |
| US20150073008A1 (en) * | 2013-09-12 | 2015-03-12 | Merz Pharma Gmbh & Co. Kgaa | Topical Application of Vinca Alkaloids for the Treatment of Actinic Keratosis |
| CN105198790B (zh) * | 2015-04-20 | 2018-02-16 | 范国煌 | 促进双阴性t细胞体外增殖的四环化合物 |
| GB201703248D0 (en) * | 2017-02-28 | 2017-04-12 | Cancer Res Inst | CHK 1 inhibition, synthetic lethality and cancer treatment |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU649116B2 (en) * | 1991-03-27 | 1994-05-12 | Sankyo Company Limited | New compounds, named the "Leustroducins", their preparation and their therapeutic uses |
| GB9718952D0 (en) * | 1997-09-05 | 1997-11-12 | Medical Res Council | Mammalian chk1 effector cell cycle checkpoint protein kinase materials and methods |
| US6071691A (en) * | 1998-04-27 | 2000-06-06 | Oregon Health Science University | Materials and methods for modulating differentiation |
| JPH11335299A (ja) * | 1998-05-26 | 1999-12-07 | Mochida Pharmaceut Co Ltd | 抗癌剤または放射線療法の副作用軽減剤 |
| JP4049477B2 (ja) * | 1999-03-23 | 2008-02-20 | 大鵬薬品工業株式会社 | 副作用軽減剤 |
| WO2001021771A2 (en) * | 1999-09-22 | 2001-03-29 | Canbas Co., Ltd. | Compositions and methods for inhibiting g2 cell cycle arrest and sensitizing cells to dna damaging agents |
| US6495586B2 (en) * | 2000-02-25 | 2002-12-17 | The Regents Of The University Of California | Scytonemin and methods of using thereof |
| US6211164B1 (en) * | 2000-03-10 | 2001-04-03 | Abbott Laboratories | Antisense oligonucleotides of the human chk1 gene and uses thereof |
| JP4625156B2 (ja) * | 2000-04-10 | 2011-02-02 | イーエヌ大塚製薬株式会社 | 癌化学療法に伴う副作用軽減剤 |
| UA76977C2 (en) * | 2001-03-02 | 2006-10-16 | Icos Corp | Aryl- and heteroaryl substituted chk1 inhibitors and their use as radiosensitizers and chemosensitizers |
| WO2003029241A1 (en) * | 2001-10-04 | 2003-04-10 | Smithkline Beecham Corporation | Chk1 kinase inhibitors |
| US20030187026A1 (en) * | 2001-12-13 | 2003-10-02 | Qun Li | Kinase inhibitors |
| US6797825B2 (en) * | 2001-12-13 | 2004-09-28 | Abbott Laboratories | Protein kinase inhibitors |
| US7202244B2 (en) * | 2002-05-29 | 2007-04-10 | Millennium Pharmaceuticals, Inc. | Chk-1 inhibitors |
| EP1539754A4 (en) * | 2002-08-23 | 2009-02-25 | Novartis Vaccines & Diagnostic | BENZIMIDAZOCHINOLINONE AND ITS USE |
-
2004
- 2004-09-17 AU AU2004274013A patent/AU2004274013A1/en not_active Abandoned
- 2004-09-17 EP EP04784613A patent/EP1667684A1/en not_active Withdrawn
- 2004-09-17 KR KR1020067007411A patent/KR20070064414A/ko not_active Withdrawn
- 2004-09-17 WO PCT/US2004/030806 patent/WO2005027907A1/en not_active Ceased
- 2004-09-17 JP JP2006527120A patent/JP2007519609A/ja active Pending
- 2004-09-17 RU RU2006112548/15A patent/RU2006112548A/ru not_active Application Discontinuation
- 2004-09-17 MX MXPA06003110A patent/MXPA06003110A/es not_active Application Discontinuation
- 2004-09-17 CA CA002539320A patent/CA2539320A1/en not_active Abandoned
- 2004-09-17 US US10/572,543 patent/US20070185013A1/en not_active Abandoned
- 2004-09-17 CN CNA200480033853XA patent/CN1882342A/zh active Pending
-
2006
- 2006-03-15 IL IL174334A patent/IL174334A0/en unknown
- 2006-03-31 NO NO20061475A patent/NO20061475L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP1667684A1 (en) | 2006-06-14 |
| JP2007519609A (ja) | 2007-07-19 |
| US20070185013A1 (en) | 2007-08-09 |
| AU2004274013A1 (en) | 2005-03-31 |
| MXPA06003110A (es) | 2006-06-20 |
| IL174334A0 (en) | 2006-08-01 |
| CN1882342A (zh) | 2006-12-20 |
| KR20070064414A (ko) | 2007-06-20 |
| NO20061475L (no) | 2006-06-13 |
| RU2006112548A (ru) | 2007-10-27 |
| WO2005027907A1 (en) | 2005-03-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2539320A1 (en) | Use of chk1 inhibitors to control cell proliferation | |
| JP5393489B2 (ja) | 蛋白キナーゼの阻害剤として有用なアミノピリミジン | |
| US7560462B2 (en) | Compounds useful for inhibiting CHK1 | |
| EP2475368B1 (en) | N-(4-((3-(2-amino-4-pyrimidinyl)-2-pyridin yl)oxy)phenyl)-4-(4-methyl-2-thienyl)-1-phthalazinamine for use in the treatment of antimitotic agent resistant cancer | |
| HUE029370T2 (hu) | Rákellenes aktivitású vegyületek | |
| JP2012529518A (ja) | ヘッジホッグシグナル伝達のピリジル−トリアジン阻害剤 | |
| RS51807B (sr) | Kombinacije za lečenje bolesti koje obuhvataju ćelijsku proliferaciju | |
| JP2014141529A (ja) | キナーゼのインヒビターとして有用なチアゾールおよびピラゾール | |
| JP2012529513A (ja) | トリアジン誘導体類及びそれらの治療応用 | |
| JP2009227682A (ja) | Chk1阻害に有用なヘテロアリール尿素誘導体 | |
| JP2012529530A (ja) | ヘッジホッグシグナル伝達の阻害剤としての、イソキノリン、キノリン及びキナゾリン誘導体 | |
| US20080318974A1 (en) | Compounds Useful for Inhibiting Chk1 | |
| JP2008535830A5 (https=) | ||
| AU2005267185A1 (en) | Bisarylurea derivatives useful for inhibiting CHK1 | |
| HK40061639B (zh) | 以杂环化合物作为激酶抑制剂的治疗用途 | |
| HK40053004A (en) | Quinoline derivatives for use in the treatment or prevention of cancer | |
| HK1119670B (en) | Heteroaryl urea derivatives useful for inhibiting chk1 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |