RU2567044C2 - Ингибиторы 1 киназы контрольной точки клеточного цикла для усиления днк-повреждающих агентов - Google Patents
Ингибиторы 1 киназы контрольной точки клеточного цикла для усиления днк-повреждающих агентов Download PDFInfo
- Publication number
- RU2567044C2 RU2567044C2 RU2011145773/15A RU2011145773A RU2567044C2 RU 2567044 C2 RU2567044 C2 RU 2567044C2 RU 2011145773/15 A RU2011145773/15 A RU 2011145773/15A RU 2011145773 A RU2011145773 A RU 2011145773A RU 2567044 C2 RU2567044 C2 RU 2567044C2
- Authority
- RU
- Russia
- Prior art keywords
- cancer
- damaging agent
- dna damaging
- use according
- bromo
- Prior art date
Links
- 239000012623 DNA damaging agent Substances 0.000 title claims abstract description 155
- 239000003112 inhibitor Substances 0.000 title claims abstract description 147
- 102100031081 Serine/threonine-protein kinase Chk1 Human genes 0.000 title claims abstract description 144
- 101000777293 Homo sapiens Serine/threonine-protein kinase Chk1 Proteins 0.000 title claims abstract description 143
- 230000003321 amplification Effects 0.000 title abstract 2
- 238000003199 nucleic acid amplification method Methods 0.000 title abstract 2
- 229960005277 gemcitabine Drugs 0.000 claims abstract description 39
- 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 abstract description 39
- 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 abstract description 28
- 229960004768 irinotecan Drugs 0.000 claims abstract description 22
- 210000004881 tumor cell Anatomy 0.000 claims abstract description 16
- 206010028980 Neoplasm Diseases 0.000 claims description 92
- 201000011510 cancer Diseases 0.000 claims description 47
- GNQGZVPEJQFMEL-UHFFFAOYSA-N 1-(2-bromo-1H-pyrrol-3-yl)piperidin-3-amine Chemical compound NC1CCCN(C1)C1=C(Br)NC=C1 GNQGZVPEJQFMEL-UHFFFAOYSA-N 0.000 claims description 24
- -1 pyridine -3-yl Chemical group 0.000 claims description 23
- 206010025323 Lymphomas Diseases 0.000 claims description 18
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 16
- 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 15
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 14
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims description 14
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 claims description 14
- 231100000682 maximum tolerated dose Toxicity 0.000 claims description 14
- 208000006990 cholangiocarcinoma Diseases 0.000 claims description 13
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 claims description 12
- 229960004117 capecitabine Drugs 0.000 claims description 12
- 229960004964 temozolomide Drugs 0.000 claims description 12
- 230000009471 action Effects 0.000 claims description 11
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 11
- 206010009944 Colon cancer Diseases 0.000 claims description 10
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 10
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 10
- 229960004316 cisplatin Drugs 0.000 claims description 10
- 229960002949 fluorouracil Drugs 0.000 claims description 10
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 9
- 206010033128 Ovarian cancer Diseases 0.000 claims description 9
- 229960004562 carboplatin Drugs 0.000 claims description 9
- 229960000684 cytarabine Drugs 0.000 claims description 9
- 208000032839 leukemia Diseases 0.000 claims description 9
- 230000035772 mutation Effects 0.000 claims description 9
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 9
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims description 8
- 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 8
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 8
- 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 claims description 8
- 229940127093 camptothecin Drugs 0.000 claims description 8
- 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 claims description 8
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 claims description 8
- 208000014018 liver neoplasm Diseases 0.000 claims description 8
- 229960003966 nicotinamide Drugs 0.000 claims description 8
- 235000005152 nicotinamide Nutrition 0.000 claims description 8
- 239000011570 nicotinamide Substances 0.000 claims description 8
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 8
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 8
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 7
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 7
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 7
- 206010017758 gastric cancer Diseases 0.000 claims description 7
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 7
- 201000002528 pancreatic cancer Diseases 0.000 claims description 7
- 208000000587 small cell lung carcinoma Diseases 0.000 claims description 7
- 201000011549 stomach cancer Diseases 0.000 claims description 7
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 6
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 6
- 206010004593 Bile duct cancer Diseases 0.000 claims description 6
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 6
- 208000032612 Glial tumor Diseases 0.000 claims description 6
- 206010018338 Glioma Diseases 0.000 claims description 6
- 206010073073 Hepatobiliary cancer Diseases 0.000 claims description 6
- 208000017604 Hodgkin disease Diseases 0.000 claims description 6
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 6
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims description 6
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 6
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 6
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 6
- 208000026900 bile duct neoplasm Diseases 0.000 claims description 6
- 230000022131 cell cycle Effects 0.000 claims description 6
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 6
- 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 6
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 5
- 206010055113 Breast cancer metastatic Diseases 0.000 claims description 5
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims description 5
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 claims description 5
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 5
- 208000024313 Testicular Neoplasms Diseases 0.000 claims description 5
- 206010057644 Testis cancer Diseases 0.000 claims description 5
- 230000005855 radiation Effects 0.000 claims description 5
- 201000003120 testicular cancer Diseases 0.000 claims description 5
- YJVHVYOXZTUFRS-UHFFFAOYSA-N 1-(2-bromo-1H-pyrrol-3-yl)-N-methylpiperidin-3-amine Chemical compound CNC1CCCN(C1)C1=C(Br)NC=C1 YJVHVYOXZTUFRS-UHFFFAOYSA-N 0.000 claims description 4
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims description 4
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 claims description 4
- 230000001684 chronic effect Effects 0.000 claims description 4
- 229960004397 cyclophosphamide Drugs 0.000 claims description 4
- AIMMVWOEOZMVMS-UHFFFAOYSA-N cyclopropanecarboxamide Chemical compound NC(=O)C1CC1 AIMMVWOEOZMVMS-UHFFFAOYSA-N 0.000 claims description 4
- 229960000975 daunorubicin Drugs 0.000 claims description 4
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims description 4
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 claims description 4
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 claims description 4
- 229940047889 isobutyramide Drugs 0.000 claims description 4
- 229960005079 pemetrexed Drugs 0.000 claims description 4
- 229960000303 topotecan Drugs 0.000 claims description 4
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 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
- 229960004630 chlorambucil Drugs 0.000 claims description 3
- 229960004679 doxorubicin Drugs 0.000 claims description 3
- 229960000390 fludarabine Drugs 0.000 claims description 3
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 claims description 3
- 229960001330 hydroxycarbamide 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
- 229960001924 melphalan Drugs 0.000 claims description 3
- 229960004857 mitomycin Drugs 0.000 claims description 3
- 201000001514 prostate carcinoma Diseases 0.000 claims description 3
- 190000008236 carboplatin Chemical compound 0.000 claims 4
- 229960005420 etoposide Drugs 0.000 claims 2
- 210000004907 gland Anatomy 0.000 claims 2
- 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 2
- QBACGOWRJDBXSG-ONEGZZNKSA-N (e)-n-[4-(3-bromo-4-chloroanilino)pyrido[3,4-d]pyrimidin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N1=CN=C2C=NC(NC(=O)/C=C/CN(C)C)=CC2=C1NC1=CC=C(Cl)C(Br)=C1 QBACGOWRJDBXSG-ONEGZZNKSA-N 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 15
- 230000000694 effects Effects 0.000 abstract description 7
- 239000003814 drug Substances 0.000 abstract description 6
- 108010019244 Checkpoint Kinase 1 Proteins 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract description 2
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 abstract 1
- 241000699670 Mus sp. Species 0.000 description 29
- 229940125782 compound 2 Drugs 0.000 description 23
- 229940125898 compound 5 Drugs 0.000 description 20
- 210000004027 cell Anatomy 0.000 description 18
- 241001465754 Metazoa Species 0.000 description 17
- 230000005764 inhibitory process Effects 0.000 description 17
- 230000037396 body weight Effects 0.000 description 15
- 201000009030 Carcinoma Diseases 0.000 description 13
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 13
- 239000002953 phosphate buffered saline Substances 0.000 description 13
- 239000003795 chemical substances by application Substances 0.000 description 12
- 230000026731 phosphorylation Effects 0.000 description 11
- 238000006366 phosphorylation reaction Methods 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 8
- 239000000945 filler Substances 0.000 description 8
- 206010041823 squamous cell carcinoma Diseases 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- 208000009956 adenocarcinoma Diseases 0.000 description 7
- DVQHYTBCTGYNNN-UHFFFAOYSA-N azane;cyclobutane-1,1-dicarboxylic acid;platinum Chemical compound N.N.[Pt].OC(=O)C1(C(O)=O)CCC1 DVQHYTBCTGYNNN-UHFFFAOYSA-N 0.000 description 7
- 230000004071 biological effect Effects 0.000 description 7
- 125000004122 cyclic group Chemical group 0.000 description 7
- 230000034994 death Effects 0.000 description 7
- 231100000517 death Toxicity 0.000 description 7
- 238000007920 subcutaneous administration Methods 0.000 description 7
- 230000004614 tumor growth Effects 0.000 description 7
- 101150012716 CDK1 gene Proteins 0.000 description 6
- 101100059559 Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) nimX gene Proteins 0.000 description 6
- 101100273808 Xenopus laevis cdk1-b gene Proteins 0.000 description 6
- 229940125904 compound 1 Drugs 0.000 description 6
- IAYGCINLNONXHY-LBPRGKRZSA-N 3-(carbamoylamino)-5-(3-fluorophenyl)-N-[(3S)-3-piperidinyl]-2-thiophenecarboxamide Chemical compound NC(=O)NC=1C=C(C=2C=C(F)C=CC=2)SC=1C(=O)N[C@H]1CCCNC1 IAYGCINLNONXHY-LBPRGKRZSA-N 0.000 description 5
- MOVBBVMDHIRCTG-LJQANCHMSA-N 4-[(3s)-1-azabicyclo[2.2.2]oct-3-ylamino]-3-(1h-benzimidazol-2-yl)-6-chloroquinolin-2(1h)-one Chemical compound C([N@](CC1)C2)C[C@@H]1[C@@H]2NC1=C(C=2NC3=CC=CC=C3N=2)C(=O)NC2=CC=C(Cl)C=C21 MOVBBVMDHIRCTG-LJQANCHMSA-N 0.000 description 5
- 206010053759 Growth retardation Diseases 0.000 description 5
- YFNWWNRZJGMDBR-LJQANCHMSA-N PF-00477736 Chemical compound C1=NN(C)C=C1C1=NC2=CC(NC(=O)[C@H](N)C3CCCCC3)=CC3=C2C1=CNNC3=O YFNWWNRZJGMDBR-LJQANCHMSA-N 0.000 description 5
- 206010039491 Sarcoma Diseases 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 231100000001 growth retardation Toxicity 0.000 description 5
- 238000003119 immunoblot Methods 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 5
- 229960001756 oxaliplatin Drugs 0.000 description 5
- 230000005778 DNA damage Effects 0.000 description 4
- 231100000277 DNA damage Toxicity 0.000 description 4
- 230000033616 DNA repair Effects 0.000 description 4
- 102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 4
- 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 4
- 101000777277 Homo sapiens Serine/threonine-protein kinase Chk2 Proteins 0.000 description 4
- 206010024612 Lipoma Diseases 0.000 description 4
- 108091000080 Phosphotransferase Proteins 0.000 description 4
- 102100031075 Serine/threonine-protein kinase Chk2 Human genes 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 229960000752 etoposide phosphate Drugs 0.000 description 4
- LIQODXNTTZAGID-OCBXBXKTSA-N etoposide phosphate Chemical compound COC1=C(OP(O)(O)=O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 LIQODXNTTZAGID-OCBXBXKTSA-N 0.000 description 4
- 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 4
- 102000020233 phosphotransferase Human genes 0.000 description 4
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 4
- MWWSFMDVAYGXBV-RUELKSSGSA-N Doxorubicin 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-RUELKSSGSA-N 0.000 description 3
- 201000008808 Fibrosarcoma Diseases 0.000 description 3
- 206010060862 Prostate cancer Diseases 0.000 description 3
- 229940126214 compound 3 Drugs 0.000 description 3
- 206010016629 fibroma Diseases 0.000 description 3
- 201000011066 hemangioma Diseases 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 201000001441 melanoma Diseases 0.000 description 3
- 201000003076 Angiosarcoma Diseases 0.000 description 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
- 201000005262 Chondroma Diseases 0.000 description 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
- 208000002927 Hamartoma Diseases 0.000 description 2
- 208000001258 Hemangiosarcoma Diseases 0.000 description 2
- 208000007766 Kaposi sarcoma Diseases 0.000 description 2
- 208000018142 Leiomyosarcoma Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 208000034578 Multiple myelomas Diseases 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 2
- 201000004404 Neurofibroma Diseases 0.000 description 2
- 208000000035 Osteochondroma Diseases 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 2
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 2
- 206010043276 Teratoma Diseases 0.000 description 2
- 208000008383 Wilms tumor Diseases 0.000 description 2
- 229940110282 alimta Drugs 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229940088954 camptosar Drugs 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 229940120655 eloxatin Drugs 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 229940020967 gemzar Drugs 0.000 description 2
- 231100000024 genotoxic Toxicity 0.000 description 2
- 230000001738 genotoxic effect Effects 0.000 description 2
- 208000005017 glioblastoma Diseases 0.000 description 2
- 229940088013 hycamtin Drugs 0.000 description 2
- 201000010260 leiomyoma Diseases 0.000 description 2
- 206010027191 meningioma Diseases 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 208000025113 myeloid leukemia Diseases 0.000 description 2
- 238000011580 nude mouse model Methods 0.000 description 2
- 208000008798 osteoma Diseases 0.000 description 2
- 201000008968 osteosarcoma Diseases 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 229940061353 temodar Drugs 0.000 description 2
- 229960001278 teniposide Drugs 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 229940053867 xeloda Drugs 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- GMIZZEXBPRLVIV-SECBINFHSA-N 6-bromo-3-(1-methylpyrazol-4-yl)-5-[(3r)-piperidin-3-yl]pyrazolo[1,5-a]pyrimidin-7-amine Chemical compound C1=NN(C)C=C1C1=C2N=C([C@H]3CNCCC3)C(Br)=C(N)N2N=C1 GMIZZEXBPRLVIV-SECBINFHSA-N 0.000 description 1
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
- 206010001233 Adenoma benign Diseases 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 101150006084 CHKB gene Proteins 0.000 description 1
- 101100220616 Caenorhabditis elegans chk-2 gene Proteins 0.000 description 1
- 208000009458 Carcinoma in Situ Diseases 0.000 description 1
- 208000010667 Carcinoma of liver and intrahepatic biliary tract Diseases 0.000 description 1
- 206010008263 Cervical dysplasia Diseases 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 102000006459 Checkpoint Kinase 1 Human genes 0.000 description 1
- 108010019243 Checkpoint Kinase 2 Proteins 0.000 description 1
- 102000006457 Checkpoint Kinase 2 Human genes 0.000 description 1
- 208000005243 Chondrosarcoma Diseases 0.000 description 1
- 201000009047 Chordoma Diseases 0.000 description 1
- 208000006332 Choriocarcinoma Diseases 0.000 description 1
- 206010048832 Colon adenoma Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 102000003915 DNA Topoisomerases Human genes 0.000 description 1
- 108090000323 DNA Topoisomerases Proteins 0.000 description 1
- 230000005971 DNA damage repair Effects 0.000 description 1
- 208000000471 Dysplastic Nevus Syndrome Diseases 0.000 description 1
- 206010062805 Dysplastic naevus Diseases 0.000 description 1
- 206010014967 Ependymoma Diseases 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- 208000007659 Fibroadenoma Diseases 0.000 description 1
- 206010053717 Fibrous histiocytoma Diseases 0.000 description 1
- 230000010190 G1 phase Effects 0.000 description 1
- 230000010337 G2 phase Effects 0.000 description 1
- 230000020172 G2/M transition checkpoint Effects 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- 208000000527 Germinoma Diseases 0.000 description 1
- 208000007569 Giant Cell Tumors Diseases 0.000 description 1
- 206010018691 Granuloma Diseases 0.000 description 1
- 208000005234 Granulosa Cell Tumor Diseases 0.000 description 1
- 206010019629 Hepatic adenoma Diseases 0.000 description 1
- 206010073069 Hepatic cancer Diseases 0.000 description 1
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
- 208000002260 Keloid Diseases 0.000 description 1
- 206010023330 Keloid scar Diseases 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 208000002404 Liver Cell Adenoma Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 208000028018 Lymphocytic leukaemia Diseases 0.000 description 1
- 208000006644 Malignant Fibrous Histiocytoma Diseases 0.000 description 1
- 208000000172 Medulloblastoma Diseases 0.000 description 1
- 206010027406 Mesothelioma Diseases 0.000 description 1
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 1
- 208000014767 Myeloproliferative disease Diseases 0.000 description 1
- 201000007224 Myeloproliferative neoplasm Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 201000010133 Oligodendroglioma Diseases 0.000 description 1
- 206010031299 Osteosis Diseases 0.000 description 1
- 206010034299 Penile cancer Diseases 0.000 description 1
- 208000007641 Pinealoma Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 208000005678 Rhabdomyoma Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 230000018199 S phase Effects 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
- 208000000097 Sertoli-Leydig cell tumor Diseases 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 208000032383 Soft tissue cancer Diseases 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 208000015778 Undifferentiated pleomorphic sarcoma Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 206010048214 Xanthoma Diseases 0.000 description 1
- 206010048215 Xanthomatosis Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000002718 adenomatoid tumor Diseases 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 201000007538 anal carcinoma Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940124650 anti-cancer therapies Drugs 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- 208000001119 benign fibrous histiocytoma Diseases 0.000 description 1
- 201000000053 blastoma Diseases 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 201000009480 botryoid rhabdomyosarcoma Diseases 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 201000003149 breast fibroadenoma Diseases 0.000 description 1
- 208000003362 bronchogenic carcinoma Diseases 0.000 description 1
- 201000002143 bronchus adenoma Diseases 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- 239000012830 cancer therapeutic Substances 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 208000019065 cervical carcinoma Diseases 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 208000009060 clear cell adenocarcinoma Diseases 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 201000010305 cutaneous fibrous histiocytoma Diseases 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 231100000371 dose-limiting toxicity Toxicity 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 201000008184 embryoma Diseases 0.000 description 1
- 201000009409 embryonal rhabdomyosarcoma Diseases 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 201000003914 endometrial carcinoma Diseases 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 201000003115 germ cell cancer Diseases 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 244000144993 groups of animals Species 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 208000006359 hepatoblastoma Diseases 0.000 description 1
- 201000002735 hepatocellular adenoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 230000037417 hyperactivation Effects 0.000 description 1
- 201000004933 in situ carcinoma Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 206010022498 insulinoma Diseases 0.000 description 1
- 210000002570 interstitial cell Anatomy 0.000 description 1
- 210000001117 keloid Anatomy 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 208000022013 kidney Wilms tumor Diseases 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 206010024627 liposarcoma Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 201000002250 liver carcinoma Diseases 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005249 lung adenocarcinoma Diseases 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 201000005243 lung squamous cell carcinoma Diseases 0.000 description 1
- 208000003747 lymphoid leukemia Diseases 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 201000000289 malignant teratoma Diseases 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 108010082117 matrigel Proteins 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000002418 meninge Anatomy 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000004001 molecular interaction Effects 0.000 description 1
- 208000010492 mucinous cystadenocarcinoma Diseases 0.000 description 1
- 208000009091 myxoma Diseases 0.000 description 1
- 201000008026 nephroblastoma Diseases 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 208000007538 neurilemmoma Diseases 0.000 description 1
- 208000004649 neutrophil actin dysfunction Diseases 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 210000003101 oviduct Anatomy 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical group C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 208000021255 pancreatic insulinoma Diseases 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 208000030940 penile carcinoma Diseases 0.000 description 1
- 201000008174 penis carcinoma Diseases 0.000 description 1
- 201000002628 peritoneum cancer Diseases 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 208000024724 pineal body neoplasm Diseases 0.000 description 1
- 201000004123 pineal gland cancer Diseases 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000032029 positive regulation of DNA repair Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000022983 regulation of cell cycle Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000028617 response to DNA damage stimulus Effects 0.000 description 1
- 208000029922 reticulum cell sarcoma Diseases 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 210000003079 salivary gland Anatomy 0.000 description 1
- 206010039667 schwannoma Diseases 0.000 description 1
- 208000004548 serous cystadenocarcinoma Diseases 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 208000001608 teratocarcinoma Diseases 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 231100000816 toxic dose Toxicity 0.000 description 1
- 206010044412 transitional cell carcinoma Diseases 0.000 description 1
- 230000016596 traversing start control point of mitotic cell cycle Effects 0.000 description 1
- 208000022271 tubular adenoma Diseases 0.000 description 1
- 210000003708 urethra Anatomy 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 206010046885 vaginal cancer Diseases 0.000 description 1
- 208000013139 vaginal neoplasm Diseases 0.000 description 1
- 208000009540 villous adenoma Diseases 0.000 description 1
- 210000003905 vulva Anatomy 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- 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
- A61K31/70—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
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Oncology (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 |
|---|---|---|---|
| US16856309P | 2009-04-11 | 2009-04-11 | |
| US61/168,563 | 2009-04-11 | ||
| PCT/US2010/030634 WO2010118390A1 (en) | 2009-04-11 | 2010-04-09 | Checkpoint kinase 1 inhibitors for potentiating dna damaging agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2011145773A RU2011145773A (ru) | 2013-05-20 |
| RU2567044C2 true RU2567044C2 (ru) | 2015-10-27 |
Family
ID=42651200
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2011145773/15A RU2567044C2 (ru) | 2009-04-11 | 2010-04-09 | Ингибиторы 1 киназы контрольной точки клеточного цикла для усиления днк-повреждающих агентов |
Country Status (15)
| Country | Link |
|---|---|
| EP (1) | EP2416773B1 (enExample) |
| JP (2) | JP5805071B2 (enExample) |
| KR (1) | KR101676062B1 (enExample) |
| CN (1) | CN102612365B (enExample) |
| AU (1) | AU2010233122B2 (enExample) |
| BR (1) | BRPI1013920A2 (enExample) |
| CA (1) | CA2758300C (enExample) |
| ES (1) | ES2608656T3 (enExample) |
| IL (1) | IL215709A (enExample) |
| MX (1) | MX341368B (enExample) |
| NZ (1) | NZ596125A (enExample) |
| RU (1) | RU2567044C2 (enExample) |
| SG (3) | SG10201900212QA (enExample) |
| WO (1) | WO2010118390A1 (enExample) |
| ZA (1) | ZA201108273B (enExample) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009089352A1 (en) | 2008-01-08 | 2009-07-16 | Array Biopharma Inc. | Pyrrolopyridines as kinase inhibitors |
| JP5608098B2 (ja) | 2008-01-09 | 2014-10-15 | アレイ バイオファーマ、インコーポレイテッド | キナーゼ阻害薬としてのピラゾロピリジン |
| US8481557B2 (en) | 2009-04-11 | 2013-07-09 | Array Biopharma Inc. | Method of treatment using checkpoint kinase 1 inhibitors |
| GB201008005D0 (en) | 2010-05-13 | 2010-06-30 | Sentinel Oncology Ltd | Pharmaceutical compounds |
| WO2012074754A1 (en) | 2010-11-16 | 2012-06-07 | Array Biopharma Inc. | Combination of checkpoint kinase 1 inhibitors and wee 1 kinase inhibitors |
| GB201119799D0 (en) | 2011-11-16 | 2011-12-28 | Sentinel Oncology Ltd | Pharmaceutical compounds |
| WO2015053402A1 (ja) | 2013-10-11 | 2015-04-16 | 国立大学法人東京医科歯科大学 | 脊髄小脳変性症を予防又は治療するための薬剤 |
| GB201402277D0 (en) | 2014-02-10 | 2014-03-26 | Sentinel Oncology Ltd | Pharmaceutical compounds |
| EP3461480A1 (en) | 2017-09-27 | 2019-04-03 | Onxeo | Combination of a dna damage response cell cycle checkpoint inhibitors and belinostat for treating cancer |
| WO2020150417A2 (en) * | 2019-01-17 | 2020-07-23 | Ifm Due, Inc. | Compounds and compositions for treating conditions associated with sting activity |
| KR102285996B1 (ko) * | 2019-08-08 | 2021-08-05 | 차의과학대학교 산학협력단 | 혈관신생을 억제하는 데 사용하기 위한 조성물 및 그 용도 |
| WO2021113661A1 (en) | 2019-12-05 | 2021-06-10 | Seagen Inc. | Amorphous and polymorphic form of a specific chk1 inhibitor |
| GB202107924D0 (en) | 2021-06-03 | 2021-07-21 | Sentinel Oncology Ltd | A pharmaceutical salt |
| TW202508595A (zh) | 2023-05-04 | 2025-03-01 | 美商銳新醫藥公司 | 用於ｒａｓ相關疾病或病症之組合療法 |
| WO2025034702A1 (en) | 2023-08-07 | 2025-02-13 | Revolution Medicines, Inc. | Rmc-6291 for use in the treatment of ras protein-related disease or disorder |
| WO2025080946A2 (en) | 2023-10-12 | 2025-04-17 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025171296A1 (en) | 2024-02-09 | 2025-08-14 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025217307A1 (en) | 2024-04-09 | 2025-10-16 | Revolution Medicines, Inc. | Methods for predicting response to a ras(on) inhibitor and combination therapies |
| WO2025240847A1 (en) | 2024-05-17 | 2025-11-20 | Revolution Medicines, Inc. | Ras inhibitors |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003028724A1 (en) * | 2001-10-04 | 2003-04-10 | Smithkline Beecham Corporation | Chk1 kinase inhibitors |
| CN1882342A (zh) * | 2003-09-17 | 2006-12-20 | 艾科斯有限公司 | Chk1抑制剂在控制细胞增殖中的应用 |
| UY29177A1 (es) * | 2004-10-25 | 2006-05-31 | Astex Therapeutics Ltd | Derivados sustituidos de purina, purinona y deazapurina, composiciones que los contienen métodos para su preparación y sus usos |
| RU2409361C2 (ru) * | 2006-04-04 | 2011-01-20 | Пфайзер Продактс Инк. | КОМБИНИРОВАННАЯ ТЕРАПИЯ (2R,Z)-2-АМИНО-2-ЦИКЛОГЕКСИЛ-N-(5-(1-МЕТИЛ-1Н-ПИРАЗОЛ-4-ИЛ)-1-ОКСО-2,6-ДИГИДРО-1Н-[1,2]ДИАЗЕПИНО[4,5,6-cd]ИНДОЛ-8-ИЛ)АЦЕТАМИДОМ |
| US20100143332A1 (en) * | 2006-11-17 | 2010-06-10 | Schering Corporation | Combination therapy for proliferative disorders |
| AR071717A1 (es) * | 2008-05-13 | 2010-07-07 | Array Biopharma Inc | Pirrolo[2,3-b]piridinas inhibidoras de quinasas chk1 y chk2,composiciones farmaceuticas que las contienen,proceso para prepararlas y uso de las mismas en el tratamiento y prevencion del cancer. |
-
2010
- 2010-04-09 SG SG10201900212QA patent/SG10201900212QA/en unknown
- 2010-04-09 KR KR1020117026769A patent/KR101676062B1/ko not_active Expired - Fee Related
- 2010-04-09 AU AU2010233122A patent/AU2010233122B2/en not_active Ceased
- 2010-04-09 NZ NZ596125A patent/NZ596125A/xx not_active IP Right Cessation
- 2010-04-09 SG SG2011075520A patent/SG175242A1/en unknown
- 2010-04-09 WO PCT/US2010/030634 patent/WO2010118390A1/en not_active Ceased
- 2010-04-09 CN CN201080025806.6A patent/CN102612365B/zh not_active Expired - Fee Related
- 2010-04-09 MX MX2011010675A patent/MX341368B/es active IP Right Grant
- 2010-04-09 SG SG10201404012RA patent/SG10201404012RA/en unknown
- 2010-04-09 BR BRPI1013920A patent/BRPI1013920A2/pt not_active Application Discontinuation
- 2010-04-09 JP JP2012504909A patent/JP5805071B2/ja not_active Expired - Fee Related
- 2010-04-09 EP EP10721579.0A patent/EP2416773B1/en active Active
- 2010-04-09 ES ES10721579.0T patent/ES2608656T3/es active Active
- 2010-04-09 RU RU2011145773/15A patent/RU2567044C2/ru active
- 2010-04-09 CA CA2758300A patent/CA2758300C/en active Active
-
2011
- 2011-10-11 IL IL215709A patent/IL215709A/en active IP Right Grant
- 2011-11-10 ZA ZA2011/08273A patent/ZA201108273B/en unknown
-
2014
- 2014-07-29 JP JP2014153687A patent/JP2014198741A/ja not_active Withdrawn
Non-Patent Citations (4)
| Title |
|---|
| MATTHEWS DJ et al. Pharmacological abrogation of S-phase check-point enhances the anti-tumor activity of gemcitabine in vivo. Cell cycle. 2007 Jan 1;6(1):104-10 [он-лайн][Найдено 2014-02-25](Найдено из Интернет: www.ncbi.nlm.nih.gov/pubmed/17245119). * |
| PARSELS LA et al.Gemcitabine sensitization by checkpoint kinase 1 inhibitorcorrelates with inhibition of Rad51 DNA damage response in pancreatic cancer cells. Mol.Cancer Ther. 2009 Jan;8(1):45-54 Реферат [он-лайн][Найдено 2014-02-25](Найдено из Интернет: www.ncbi.nlm.nih.gov/pubmed/19139112). * |
| pеферат * |
| SABLUDOFF SD et al.AZD7762, a novel checkpoint kinase inhibitor, drives checkpointabrogation and potentiates DNA-targeted therapies. Mol.Cancer Ther. 2008 Sep;7(9):2955-66 [он-лайн][Найдено 2014-02-25](Найдено из Интернет: www.ncbi.nlm.nih.gov/pubmed/18790776). * |
Also Published As
| Publication number | Publication date |
|---|---|
| RU2011145773A (ru) | 2013-05-20 |
| JP5805071B2 (ja) | 2015-11-04 |
| SG10201404012RA (en) | 2014-09-26 |
| EP2416773A1 (en) | 2012-02-15 |
| MX341368B (es) | 2016-08-17 |
| IL215709A (en) | 2017-06-29 |
| SG10201900212QA (en) | 2019-02-27 |
| AU2010233122A1 (en) | 2011-11-24 |
| IL215709A0 (en) | 2012-01-31 |
| EP2416773B1 (en) | 2016-09-28 |
| JP2012523435A (ja) | 2012-10-04 |
| BRPI1013920A2 (pt) | 2016-04-05 |
| AU2010233122B2 (en) | 2015-09-17 |
| ES2608656T3 (es) | 2017-04-12 |
| WO2010118390A1 (en) | 2010-10-14 |
| JP2014198741A (ja) | 2014-10-23 |
| CN102612365A (zh) | 2012-07-25 |
| CA2758300C (en) | 2017-07-25 |
| NZ596125A (en) | 2012-08-31 |
| CN102612365B (zh) | 2017-04-12 |
| KR101676062B1 (ko) | 2016-11-14 |
| SG175242A1 (en) | 2011-11-28 |
| ZA201108273B (en) | 2013-07-31 |
| CA2758300A1 (en) | 2010-10-14 |
| KR20120004523A (ko) | 2012-01-12 |
| MX2011010675A (es) | 2012-03-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2567044C2 (ru) | Ингибиторы 1 киназы контрольной точки клеточного цикла для усиления днк-повреждающих агентов | |
| RU2627841C2 (ru) | Комбинация ингибиторов чекпойнт-киназы 1 и ингибиторов киназы wee 1 | |
| JP6637884B2 (ja) | ブロモドメインおよびエクストラターミナル（ｂｅｔ）タンパク質インヒビターを使用するがんのための併用療法 | |
| US9155726B2 (en) | Method of treatment using checkpoint kinase 1 inhibitors | |
| EP3110509B1 (en) | Treating cancer with a combination comprising dinaciclib | |
| JP2013515690A (ja) | アルテミシニンベースの薬剤と他の化学療法薬の抗癌用組合せ | |
| HK1259445A1 (zh) | 治疗癌症的组合 | |
| CN112022871A (zh) | 金诺芬在制备用于治疗去势抵抗性前列腺癌药物中的应用 | |
| US20100286038A1 (en) | Formulation containing cyclin-dependent kinase inhibiting compound and method of treating tumors using the same | |
| RU2754131C1 (ru) | Комбинированная терапия ингибитором ezh2 | |
| WO2016035996A1 (ko) | 실로스타졸을 유효성분으로 포함하는 독소루비신에 의한 심부전 또는 확장성 심근병증의 예방용 약학 조성물 | |
| HK1165273B (en) | Checkpoint kinase 1 inhibitors for potentiating dna damaging agents | |
| CN118976012A (zh) | 一种gsdmd抑制剂预防化疗时外周神经损伤的用途 | |
| HK40081984B (zh) | 丁基苯酞及其衍生物的用途 | |
| HK1183792B (en) | Combination of checkpoint kinase 1 inhibitors and wee 1 kinase inhibitors | |
| HK1183792A (en) | Combination of checkpoint kinase 1 inhibitors and wee 1 kinase inhibitors |