JP2017502016A5 - - Google Patents
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- JP2017502016A5 JP2017502016A5 JP2016540574A JP2016540574A JP2017502016A5 JP 2017502016 A5 JP2017502016 A5 JP 2017502016A5 JP 2016540574 A JP2016540574 A JP 2016540574A JP 2016540574 A JP2016540574 A JP 2016540574A JP 2017502016 A5 JP2017502016 A5 JP 2017502016A5
- Authority
- JP
- Japan
- Prior art keywords
- inhibitor
- cas number
- delta
- cancer
- intellikine
- 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.)
- Pending
Links
- 239000003814 drug Substances 0.000 claims description 178
- 239000003112 inhibitor Substances 0.000 claims description 164
- 230000037361 pathway Effects 0.000 claims description 118
- 206010028980 Neoplasm Diseases 0.000 claims description 63
- 201000011510 cancer Diseases 0.000 claims description 63
- 239000002246 antineoplastic agent Substances 0.000 claims description 60
- 150000003839 salts Chemical group 0.000 claims description 52
- 229940126656 GS-4224 Drugs 0.000 claims description 50
- 229940118166 PI3 kinase delta inhibitor Drugs 0.000 claims description 40
- 102000038030 PI3Ks Human genes 0.000 claims description 40
- 108091007960 PI3Ks Proteins 0.000 claims description 40
- 239000003795 chemical substances by application Substances 0.000 claims description 34
- 229940124597 therapeutic agent Drugs 0.000 claims description 30
- 241000124008 Mammalia Species 0.000 claims description 26
- 239000008194 pharmaceutical composition Substances 0.000 claims description 25
- 229940124647 MEK inhibitor Drugs 0.000 claims description 24
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 claims description 24
- -1 radionuclides Substances 0.000 claims description 21
- SRLVNYDXMUGOFI-XBXARRHUSA-N (5e)-5-[(2,2-difluoro-1,3-benzodioxol-5-yl)methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1=C2OC(F)(F)OC2=CC=C1\C=C1\SC(=O)NC1=O SRLVNYDXMUGOFI-XBXARRHUSA-N 0.000 claims description 20
- LFWGZXMTCUOPFI-UHFFFAOYSA-N 2,3-diphenyl-6-quinoxalinecarboxylic acid Chemical compound C=1C=CC=CC=1C1=NC2=CC(C(=O)O)=CC=C2N=C1C1=CC=CC=C1 LFWGZXMTCUOPFI-UHFFFAOYSA-N 0.000 claims description 20
- KGPGFQWBCSZGEL-ZDUSSCGKSA-N GSK690693 Chemical compound C=12N(CC)C(C=3C(=NON=3)N)=NC2=C(C#CC(C)(C)O)N=CC=1OC[C@H]1CCCNC1 KGPGFQWBCSZGEL-ZDUSSCGKSA-N 0.000 claims description 20
- ZHEHVZXPFVXKEY-RUAOOFDTSA-N KT 5720 Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@@H]1C[C@](C(=O)OCCCCCC)(O)[C@@]4(C)O1 ZHEHVZXPFVXKEY-RUAOOFDTSA-N 0.000 claims description 20
- 241001465754 Metazoa Species 0.000 claims description 20
- 230000000694 effects Effects 0.000 claims description 20
- 229960003445 idelalisib Drugs 0.000 claims description 20
- YKLIKGKUANLGSB-HNNXBMFYSA-N idelalisib Chemical compound C1([C@@H](NC=2[C]3N=CN=C3N=CN=2)CC)=NC2=CC=CC(F)=C2C(=O)N1C1=CC=CC=C1 YKLIKGKUANLGSB-HNNXBMFYSA-N 0.000 claims description 20
- 230000035772 mutation Effects 0.000 claims description 20
- 239000002935 phosphatidylinositol 3 kinase inhibitor Substances 0.000 claims description 20
- 230000000392 somatic effect Effects 0.000 claims description 20
- LBTVHXHERHESKG-UHFFFAOYSA-N tetrahydrocurcumin Chemical compound C1=C(O)C(OC)=CC(CCC(=O)CC(=O)CCC=2C=C(OC)C(O)=CC=2)=C1 LBTVHXHERHESKG-UHFFFAOYSA-N 0.000 claims description 20
- 229940116355 PI3 kinase inhibitor Drugs 0.000 claims description 19
- KSERXGMCDHOLSS-LJQANCHMSA-N n-[(1s)-1-(3-chlorophenyl)-2-hydroxyethyl]-4-[5-chloro-2-(propan-2-ylamino)pyridin-4-yl]-1h-pyrrole-2-carboxamide Chemical compound C1=NC(NC(C)C)=CC(C=2C=C(NC=2)C(=O)N[C@H](CO)C=2C=C(Cl)C=CC=2)=C1Cl KSERXGMCDHOLSS-LJQANCHMSA-N 0.000 claims description 13
- ZKZXNDJNWUTGDK-NSCUHMNNSA-N (E)-N-[2-(4-bromocinnamylamino)ethyl]isoquinoline-5-sulfonamide Chemical compound C1=CC(Br)=CC=C1\C=C\CNCCNS(=O)(=O)C1=CC=CC2=CN=CC=C12 ZKZXNDJNWUTGDK-NSCUHMNNSA-N 0.000 claims description 11
- IUGRBTCJEYEDIY-VZUCSPMQSA-N (e)-2-(3,4-dihydroxybenzoyl)-3-(2-oxo-3h-1,3-benzoxazol-5-yl)prop-2-enenitrile Chemical compound C1=C(O)C(O)=CC=C1C(=O)C(\C#N)=C\C1=CC=C(OC(=O)N2)C2=C1 IUGRBTCJEYEDIY-VZUCSPMQSA-N 0.000 claims description 10
- SCSSXJVRZMQUKA-UHFFFAOYSA-N 2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-pyridin-4-ylpropanoic acid Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1COC(=O)NC(C(=O)O)CC1=CC=NC=C1 SCSSXJVRZMQUKA-UHFFFAOYSA-N 0.000 claims description 10
- PUYVJBBSBPUKBT-AWEZNQCLSA-N 2-[(1s)-1-[(2-amino-7h-purin-6-yl)amino]ethyl]-5-methyl-3-(2-methylphenyl)quinazolin-4-one Chemical compound C1([C@@H](NC=2C=3NC=NC=3N=C(N)N=2)C)=NC2=CC=CC(C)=C2C(=O)N1C1=CC=CC=C1C PUYVJBBSBPUKBT-AWEZNQCLSA-N 0.000 claims description 10
- RZIDZIGAXXNODG-UHFFFAOYSA-N 4-[(4-chlorophenyl)methyl]-1-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-amine Chemical compound C1CN(C=2C=3C=CNC=3N=CN=2)CCC1(N)CC1=CC=C(Cl)C=C1 RZIDZIGAXXNODG-UHFFFAOYSA-N 0.000 claims description 10
- BYWWNRBKPCPJMG-UHFFFAOYSA-N 4-dodecyl-n-(1,3,4-thiadiazol-2-yl)benzenesulfonamide Chemical compound C1=CC(CCCCCCCCCCCC)=CC=C1S(=O)(=O)NC1=NN=CS1 BYWWNRBKPCPJMG-UHFFFAOYSA-N 0.000 claims description 10
- SDGWAUUPHUBJNQ-UHFFFAOYSA-N 5-(1,3-benzodioxol-5-ylmethylidene)-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1=CC1=CC=C(OCO2)C2=C1 SDGWAUUPHUBJNQ-UHFFFAOYSA-N 0.000 claims description 10
- DOCINCLJNAXZQF-LBPRGKRZSA-N 6-fluoro-3-phenyl-2-[(1s)-1-(7h-purin-6-ylamino)ethyl]quinazolin-4-one Chemical compound C1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)=NC2=CC=C(F)C=C2C(=O)N1C1=CC=CC=C1 DOCINCLJNAXZQF-LBPRGKRZSA-N 0.000 claims description 10
- HWUHTJIKQZZBRA-UHFFFAOYSA-N 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-2h-[1,2,4]triazolo[3,4-f][1,6]naphthyridin-3-one;dihydrochloride Chemical compound Cl.Cl.C=1C=C(C=2C(=CC=3C=4N(C(NN=4)=O)C=CC=3N=2)C=2C=CC=CC=2)C=CC=1C1(N)CCC1 HWUHTJIKQZZBRA-UHFFFAOYSA-N 0.000 claims description 10
- SJVQHLPISAIATJ-ZDUSSCGKSA-N 8-chloro-2-phenyl-3-[(1S)-1-(7H-purin-6-ylamino)ethyl]-1-isoquinolinone Chemical compound C1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)=CC2=CC=CC(Cl)=C2C(=O)N1C1=CC=CC=C1 SJVQHLPISAIATJ-ZDUSSCGKSA-N 0.000 claims description 10
- 229960005531 AMG 319 Drugs 0.000 claims description 10
- 206010006187 Breast cancer Diseases 0.000 claims description 10
- 208000026310 Breast neoplasm Diseases 0.000 claims description 10
- 206010009944 Colon cancer Diseases 0.000 claims description 10
- 206010014733 Endometrial cancer Diseases 0.000 claims description 10
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 10
- BYTORXDZJWWIKR-UHFFFAOYSA-N Hinokiol Natural products CC(C)c1cc2CCC3C(C)(CO)C(O)CCC3(C)c2cc1O BYTORXDZJWWIKR-UHFFFAOYSA-N 0.000 claims description 10
- 241000282412 Homo Species 0.000 claims description 10
- 101000984753 Homo sapiens Serine/threonine-protein kinase B-raf Proteins 0.000 claims description 10
- 101150093335 KIN1 gene Proteins 0.000 claims description 10
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 10
- 206010025323 Lymphomas Diseases 0.000 claims description 10
- 206010029260 Neuroblastoma Diseases 0.000 claims description 10
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 10
- 241000288906 Primates Species 0.000 claims description 10
- 102100027103 Serine/threonine-protein kinase B-raf Human genes 0.000 claims description 10
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 10
- 208000024313 Testicular Neoplasms Diseases 0.000 claims description 10
- 206010057644 Testis cancer Diseases 0.000 claims description 10
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 10
- 239000004037 angiogenesis inhibitor Substances 0.000 claims description 10
- 208000029742 colonic neoplasm Diseases 0.000 claims description 10
- 239000002254 cytotoxic agent Substances 0.000 claims description 10
- 229940127089 cytotoxic agent Drugs 0.000 claims description 10
- 231100000599 cytotoxic agent Toxicity 0.000 claims description 10
- 239000012634 fragment Substances 0.000 claims description 10
- FVYXIJYOAGAUQK-UHFFFAOYSA-N honokiol Chemical compound C1=C(CC=C)C(O)=CC=C1C1=CC(CC=C)=CC=C1O FVYXIJYOAGAUQK-UHFFFAOYSA-N 0.000 claims description 10
- VVOAZFWZEDHOOU-UHFFFAOYSA-N honokiol Natural products OC1=CC=C(CC=C)C=C1C1=CC(CC=C)=CC=C1O VVOAZFWZEDHOOU-UHFFFAOYSA-N 0.000 claims description 10
- 239000005556 hormone Substances 0.000 claims description 10
- 229940088597 hormone Drugs 0.000 claims description 10
- 239000002955 immunomodulating agent Substances 0.000 claims description 10
- 229940121354 immunomodulator Drugs 0.000 claims description 10
- 208000032839 leukemia Diseases 0.000 claims description 10
- 201000007270 liver cancer Diseases 0.000 claims description 10
- 208000014018 liver neoplasm Diseases 0.000 claims description 10
- 201000005202 lung cancer Diseases 0.000 claims description 10
- 208000020816 lung neoplasm Diseases 0.000 claims description 10
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 10
- 201000001441 melanoma Diseases 0.000 claims description 10
- 229960003775 miltefosine Drugs 0.000 claims description 10
- KWRYMZHCQIOOEB-LBPRGKRZSA-N n-[(1s)-1-(7-fluoro-2-pyridin-2-ylquinolin-3-yl)ethyl]-7h-purin-6-amine Chemical compound C1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)=CC2=CC=C(F)C=C2N=C1C1=CC=CC=N1 KWRYMZHCQIOOEB-LBPRGKRZSA-N 0.000 claims description 10
- 201000002528 pancreatic cancer Diseases 0.000 claims description 10
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 10
- SZFPYBIJACMNJV-UHFFFAOYSA-N perifosine Chemical compound CCCCCCCCCCCCCCCCCCOP([O-])(=O)OC1CC[N+](C)(C)CC1 SZFPYBIJACMNJV-UHFFFAOYSA-N 0.000 claims description 10
- 229950010632 perifosine Drugs 0.000 claims description 10
- 201000000849 skin cancer Diseases 0.000 claims description 10
- 230000002195 synergetic effect Effects 0.000 claims description 10
- 201000003120 testicular cancer Diseases 0.000 claims description 10
- 201000002510 thyroid cancer Diseases 0.000 claims description 10
- 239000003053 toxin Substances 0.000 claims description 10
- 231100000765 toxin Toxicity 0.000 claims description 10
- 108700012359 toxins Proteins 0.000 claims description 10
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 claims description 9
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 claims description 9
- PQLXHQMOHUQAKB-UHFFFAOYSA-N miltefosine Chemical compound CCCCCCCCCCCCCCCCOP([O-])(=O)OCC[N+](C)(C)C PQLXHQMOHUQAKB-UHFFFAOYSA-N 0.000 claims description 9
- 239000000575 pesticide Substances 0.000 claims description 9
- 229950003873 triciribine Drugs 0.000 claims description 9
- HOGVTUZUJGHKPL-HTVVRFAVSA-N triciribine Chemical compound C=12C3=NC=NC=1N(C)N=C(N)C2=CN3[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O HOGVTUZUJGHKPL-HTVVRFAVSA-N 0.000 claims description 9
- XCPPIJCBCWUBNT-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-[2-[[4-(morpholin-4-ylmethyl)phenyl]methoxy]pyrimidin-4-yl]acetonitrile Chemical group N=1C2=CC=CC=C2SC=1C(C#N)C(N=1)=CC=NC=1OCC(C=C1)=CC=C1CN1CCOCC1 XCPPIJCBCWUBNT-UHFFFAOYSA-N 0.000 claims description 7
- 229950006785 bentamapimod Drugs 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 239000002552 dosage form Substances 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 4
- 230000004611 cancer cell death Effects 0.000 claims description 2
- FCKJZIRDZMVDEM-UHFFFAOYSA-N N-(7,8-dimethoxy-2,3-dihydro-1H-imidazo[1,2-c]quinazolin-5-ylidene)pyridine-3-carboxamide Chemical compound COC1=C(C2=NC(=NC(=O)C3=CN=CC=C3)N4CCNC4=C2C=C1)OC FCKJZIRDZMVDEM-UHFFFAOYSA-N 0.000 claims 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361919606P | 2013-12-20 | 2013-12-20 | |
| US61/919,606 | 2013-12-20 | ||
| PCT/US2014/071744 WO2015095838A2 (en) | 2013-12-20 | 2014-12-19 | Cancer treatments using combinations of mek type i and erk inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2017502016A JP2017502016A (ja) | 2017-01-19 |
| JP2017502016A5 true JP2017502016A5 (OSRAM) | 2018-02-01 |
Family
ID=53403902
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016540574A Pending JP2017502016A (ja) | 2013-12-20 | 2014-12-19 | １型ｍｅｋ阻害剤およびｅｒｋ阻害剤の組み合わせを使用するがんの処置 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20160310477A1 (OSRAM) |
| EP (1) | EP3082422A4 (OSRAM) |
| JP (1) | JP2017502016A (OSRAM) |
| AU (1) | AU2014368925A1 (OSRAM) |
| WO (1) | WO2015095838A2 (OSRAM) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101660050B1 (ko) | 2008-01-04 | 2016-09-26 | 인텔리카인, 엘엘씨 | 특정 화학 물질, 조성물 및 방법 |
| US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
| NZ612909A (en) | 2011-01-10 | 2015-09-25 | Infinity Pharmaceuticals Inc | Processes for preparing isoquinolinones and solid forms of isoquinolinones |
| US8828998B2 (en) | 2012-06-25 | 2014-09-09 | Infinity Pharmaceuticals, Inc. | Treatment of lupus, fibrotic conditions, and inflammatory myopathies and other disorders using PI3 kinase inhibitors |
| PL2914296T5 (pl) | 2012-11-01 | 2022-01-17 | Infinity Pharmaceuticals, Inc. | Leczenie nowotworu z zastosowaniem modulatorów izoform kinazy PI3 |
| WO2015160975A2 (en) | 2014-04-16 | 2015-10-22 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| IL263680B1 (en) | 2016-06-24 | 2025-06-01 | Infinity Pharmaceuticals Inc | Pi3k inhibitors for use in combination with a second therapeutic agent in treating, managing, or preventing cancer |
| CN110799245B (zh) * | 2017-05-16 | 2022-08-09 | 生物医学谷探索股份有限公司 | 用于治疗具有非典型braf突变的癌症的组合物和方法 |
| CN112402413B (zh) * | 2020-11-26 | 2022-03-08 | 重庆三峡医药高等专科学校 | 野马追倍半萜内酯b在制备抗肝癌药物中的应用及一种抗肝癌药物 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1110957A1 (en) * | 1999-12-24 | 2001-06-27 | Applied Research Systems ARS Holding N.V. | Benzazole derivatives and their use as JNK modulators |
| WO2004004644A2 (en) * | 2002-07-05 | 2004-01-15 | Beth Israel Deaconess Medical Center | Combination of mtor inhibitor and a tyrosine kinase inhibitor for the treatment of neoplasms |
| EP3943489A1 (en) * | 2004-05-14 | 2022-01-26 | Vertex Pharmaceuticals Incorporated | Pyrrole inhibitors of erk protein kinase, synthesis thereof and intermediates thereto |
| US20060079494A1 (en) * | 2004-09-27 | 2006-04-13 | Santi Daniel V | Specific kinase inhibitors |
| WO2008067069A2 (en) * | 2006-10-19 | 2008-06-05 | Oregon Health & Science University | Mitogen activated protein kinase phosphatase 4 (mkp4) and methods of use thereof |
| AR068046A1 (es) * | 2007-06-05 | 2009-11-04 | Schering Corp | Derivados policiclicos de indazol y su uso como inhibidores de erk para el tratamiento del cancer |
| AP2011005808A0 (en) * | 2009-02-26 | 2011-08-31 | Boehringer Ingelheim Int | Compounds as bradykinin B1 antagonists. |
| AU2010299835A1 (en) * | 2009-09-28 | 2012-04-05 | Centre National De La Recherche Scientifique | Irreversible inhibitors useful for the treatment of kinase-related pathologies |
| JP5719028B2 (ja) * | 2010-10-06 | 2015-05-13 | グラクソスミスクライン エルエルシー | Ｐｉ３キナーゼ阻害剤としてのベンズイミダゾール誘導体 |
-
2014
- 2014-12-19 JP JP2016540574A patent/JP2017502016A/ja active Pending
- 2014-12-19 US US15/105,945 patent/US20160310477A1/en not_active Abandoned
- 2014-12-19 WO PCT/US2014/071744 patent/WO2015095838A2/en active Application Filing
- 2014-12-19 AU AU2014368925A patent/AU2014368925A1/en not_active Abandoned
- 2014-12-19 EP EP14871339.9A patent/EP3082422A4/en not_active Withdrawn
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