JP2017502014A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2017502014A5 JP2017502014A5 JP2016540554A JP2016540554A JP2017502014A5 JP 2017502014 A5 JP2017502014 A5 JP 2017502014A5 JP 2016540554 A JP2016540554 A JP 2016540554A JP 2016540554 A JP2016540554 A JP 2016540554A JP 2017502014 A5 JP2017502014 A5 JP 2017502014A5
- Authority
- JP
- Japan
- Prior art keywords
- inhibitor
- cancer
- delta
- cas number
- therapeutics
- 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.)
- Granted
Links
- 239000003112 inhibitor Substances 0.000 claims description 258
- 239000003814 drug Substances 0.000 claims description 240
- 230000037361 pathway Effects 0.000 claims description 181
- 206010028980 Neoplasm Diseases 0.000 claims description 102
- 201000011510 cancer Diseases 0.000 claims description 102
- 238000000034 method Methods 0.000 claims description 83
- 239000002246 antineoplastic agent Substances 0.000 claims description 71
- 150000003839 salts Chemical class 0.000 claims description 71
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims description 70
- 102000010400 1-phosphatidylinositol-3-kinase activity proteins Human genes 0.000 claims description 60
- 229940126656 GS-4224 Drugs 0.000 claims description 60
- 108091007960 PI3Ks Proteins 0.000 claims description 60
- 229940118166 PI3 kinase delta inhibitor Drugs 0.000 claims description 48
- 239000003795 chemical substances by application Substances 0.000 claims description 47
- 101150015280 Cel gene Proteins 0.000 claims description 43
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims description 42
- 229960002930 sirolimus Drugs 0.000 claims description 42
- 230000000392 somatic effect Effects 0.000 claims description 42
- 229940124597 therapeutic agent Drugs 0.000 claims description 42
- -1 radionuclides Substances 0.000 claims description 41
- 241000124008 Mammalia Species 0.000 claims description 38
- 206010009944 Colon cancer Diseases 0.000 claims description 36
- 229940116355 PI3 kinase inhibitor Drugs 0.000 claims description 35
- 239000002935 phosphatidylinositol 3 kinase inhibitor Substances 0.000 claims description 35
- 208000029742 colonic neoplasm Diseases 0.000 claims description 34
- 206010069755 K-ras gene mutation Diseases 0.000 claims description 30
- 241001465754 Metazoa Species 0.000 claims description 28
- 102100023085 Serine/threonine-protein kinase mTOR Human genes 0.000 claims description 28
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 claims description 28
- LHNIIDJUOCFXAP-UHFFFAOYSA-N pictrelisib Chemical compound C1CN(S(=O)(=O)C)CCN1CC1=CC2=NC(C=3C=4C=NNC=4C=CC=3)=NC(N3CCOCC3)=C2S1 LHNIIDJUOCFXAP-UHFFFAOYSA-N 0.000 claims description 28
- YYSFXUWWPNHNAZ-PKJQJFMNSA-N umirolimus Chemical compound C1[C@@H](OC)[C@H](OCCOCC)CC[C@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 YYSFXUWWPNHNAZ-PKJQJFMNSA-N 0.000 claims description 28
- 230000000694 effects Effects 0.000 claims description 26
- 230000035772 mutation Effects 0.000 claims description 26
- 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 24
- 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 24
- 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 24
- 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 24
- 229960003445 idelalisib Drugs 0.000 claims description 24
- 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 24
- 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 24
- 239000008194 pharmaceutical composition Substances 0.000 claims description 23
- 101000605639 Homo sapiens Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Proteins 0.000 claims description 20
- 102100038332 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Human genes 0.000 claims description 20
- 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 16
- YOVVNQKCSKSHKT-HNNXBMFYSA-N (2s)-1-[4-[[2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl]piperazin-1-yl]-2-hydroxypropan-1-one Chemical compound C1CN(C(=O)[C@@H](O)C)CCN1CC1=C(C)C2=NC(C=3C=NC(N)=NC=3)=NC(N3CCOCC3)=C2S1 YOVVNQKCSKSHKT-HNNXBMFYSA-N 0.000 claims description 14
- DWZAEMINVBZMHQ-UHFFFAOYSA-N 1-[4-[4-(dimethylamino)piperidine-1-carbonyl]phenyl]-3-[4-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)phenyl]urea Chemical compound C1CC(N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC(=O)NC1=CC=C(C=2N=C(N=C(N=2)N2CCOCC2)N2CCOCC2)C=C1 DWZAEMINVBZMHQ-UHFFFAOYSA-N 0.000 claims description 14
- JUSFANSTBFGBAF-IRXDYDNUSA-N 3-[2,4-bis[(3s)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl]-n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC(C=2N=C3N=C(N=C(C3=CC=2)N2[C@H](COCC2)C)N2[C@H](COCC2)C)=C1 JUSFANSTBFGBAF-IRXDYDNUSA-N 0.000 claims description 14
- IMXHGCRIEAKIBU-UHFFFAOYSA-N 4-[6-[4-(methoxycarbonylamino)phenyl]-4-(4-morpholinyl)-1-pyrazolo[3,4-d]pyrimidinyl]-1-piperidinecarboxylic acid methyl ester Chemical compound C1=CC(NC(=O)OC)=CC=C1C1=NC(N2CCOCC2)=C(C=NN2C3CCN(CC3)C(=O)OC)C2=N1 IMXHGCRIEAKIBU-UHFFFAOYSA-N 0.000 claims description 14
- ADGGYDAFIHSYFI-UHFFFAOYSA-N 5-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine Chemical compound C1=NC(N)=CC(C(F)(F)F)=C1C1=NC(N2CCOCC2)=NC(N2CCOCC2)=N1 ADGGYDAFIHSYFI-UHFFFAOYSA-N 0.000 claims description 14
- GYLDXIAOMVERTK-UHFFFAOYSA-N 5-(4-amino-1-propan-2-yl-3-pyrazolo[3,4-d]pyrimidinyl)-1,3-benzoxazol-2-amine Chemical compound C12=C(N)N=CN=C2N(C(C)C)N=C1C1=CC=C(OC(N)=N2)C2=C1 GYLDXIAOMVERTK-UHFFFAOYSA-N 0.000 claims description 14
- LGWACEZVCMBSKW-UHFFFAOYSA-N 5-(6,6-dimethyl-4-morpholin-4-yl-8,9-dihydropurino[8,9-c][1,4]oxazin-2-yl)pyrimidin-2-amine Chemical compound CC1(C)OCCN(C2=N3)C1=NC2=C(N1CCOCC1)N=C3C1=CN=C(N)N=C1 LGWACEZVCMBSKW-UHFFFAOYSA-N 0.000 claims description 14
- XOZLHJMDLKDZAL-UHFFFAOYSA-N 5-[6-(3-methoxyoxetan-3-yl)-7-methyl-4-morpholin-4-ylthieno[3,2-d]pyrimidin-2-yl]pyrimidin-2-amine Chemical compound S1C2=C(N3CCOCC3)N=C(C=3C=NC(N)=NC=3)N=C2C(C)=C1C1(OC)COC1 XOZLHJMDLKDZAL-UHFFFAOYSA-N 0.000 claims description 14
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 claims description 14
- 241000282412 Homo Species 0.000 claims description 14
- 241000288906 Primates Species 0.000 claims description 14
- CBPNZQVSJQDFBE-FUXHJELOSA-N Temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 claims description 14
- 239000004037 angiogenesis inhibitor Substances 0.000 claims description 14
- 239000002254 cytotoxic agent Substances 0.000 claims description 14
- 229940127089 cytotoxic agent Drugs 0.000 claims description 14
- 231100000599 cytotoxic agent Toxicity 0.000 claims description 14
- 229940079593 drug Drugs 0.000 claims description 14
- 229960005167 everolimus Drugs 0.000 claims description 14
- 239000012634 fragment Substances 0.000 claims description 14
- 239000005556 hormone Substances 0.000 claims description 14
- 229940088597 hormone Drugs 0.000 claims description 14
- 239000002955 immunomodulating agent Substances 0.000 claims description 14
- 229940121354 immunomodulator Drugs 0.000 claims description 14
- 229960000901 mepacrine Drugs 0.000 claims description 14
- VDOCQQKGPJENHJ-UHFFFAOYSA-N methyl n-[4-[4-morpholin-4-yl-1-[1-(pyridin-3-ylmethyl)piperidin-4-yl]pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]carbamate Chemical compound C1=CC(NC(=O)OC)=CC=C1C1=NC(N2CCOCC2)=C(C=NN2C3CCN(CC=4C=NC=CC=4)CC3)C2=N1 VDOCQQKGPJENHJ-UHFFFAOYSA-N 0.000 claims description 14
- GDCJHDUWWAKBIW-UHFFFAOYSA-N n-[4-[4-[2-(difluoromethyl)-4-methoxybenzimidazol-1-yl]-6-morpholin-4-yl-1,3,5-triazin-2-yl]phenyl]-2-(dimethylamino)ethanesulfonamide Chemical compound FC(F)C1=NC=2C(OC)=CC=CC=2N1C(N=1)=NC(N2CCOCC2)=NC=1C1=CC=C(NS(=O)(=O)CCN(C)C)C=C1 GDCJHDUWWAKBIW-UHFFFAOYSA-N 0.000 claims description 14
- 239000002159 nanocrystal Substances 0.000 claims description 14
- WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 claims description 14
- GPKJTRJOBQGKQK-UHFFFAOYSA-N quinacrine Chemical compound C1=C(OC)C=C2C(NC(C)CCCN(CC)CC)=C(C=CC(Cl)=C3)C3=NC2=C1 GPKJTRJOBQGKQK-UHFFFAOYSA-N 0.000 claims description 14
- 229950009216 sapanisertib Drugs 0.000 claims description 14
- 230000002195 synergetic effect Effects 0.000 claims description 14
- 229960000235 temsirolimus Drugs 0.000 claims description 14
- QFJCIRLUMZQUOT-UHFFFAOYSA-N temsirolimus Natural products C1CC(O)C(OC)CC1CC(C)C1OC(=O)C2CCCCN2C(=O)C(=O)C(O)(O2)C(C)CCC2CC(OC)C(C)=CC=CC=CC(C)CC(C)C(=O)C(OC)C(O)C(C)=CC(C)C(=O)C1 QFJCIRLUMZQUOT-UHFFFAOYSA-N 0.000 claims description 14
- 239000003053 toxin Substances 0.000 claims description 14
- 231100000765 toxin Toxicity 0.000 claims description 14
- 108700012359 toxins Proteins 0.000 claims description 14
- 229950007775 umirolimus Drugs 0.000 claims description 14
- CGTADGCBEXYWNE-JUKNQOCSSA-N zotarolimus Chemical compound N1([C@H]2CC[C@@H](C[C@@H](C)[C@H]3OC(=O)[C@@H]4CCCCN4C(=O)C(=O)[C@@]4(O)[C@H](C)CC[C@H](O4)C[C@@H](/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C3)OC)C[C@H]2OC)C=NN=N1 CGTADGCBEXYWNE-JUKNQOCSSA-N 0.000 claims description 14
- 229950009819 zotarolimus Drugs 0.000 claims description 14
- 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 13
- 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 12
- 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 12
- 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 12
- 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 12
- 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 12
- 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 12
- 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 12
- 229960005531 AMG 319 Drugs 0.000 claims description 12
- 206010006187 Breast cancer Diseases 0.000 claims description 12
- 208000026310 Breast neoplasm Diseases 0.000 claims description 12
- 206010014733 Endometrial cancer Diseases 0.000 claims description 12
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 12
- BYTORXDZJWWIKR-UHFFFAOYSA-N Hinokiol Natural products CC(C)c1cc2CCC3C(C)(CO)C(O)CCC3(C)c2cc1O BYTORXDZJWWIKR-UHFFFAOYSA-N 0.000 claims description 12
- 101150093335 KIN1 gene Proteins 0.000 claims description 12
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 12
- 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 description 12
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 12
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 12
- 206010017758 gastric cancer Diseases 0.000 claims description 12
- 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 12
- 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 12
- 208000032839 leukemia Diseases 0.000 claims description 12
- 201000007270 liver cancer Diseases 0.000 claims description 12
- 208000014018 liver neoplasm Diseases 0.000 claims description 12
- 201000005202 lung cancer Diseases 0.000 claims description 12
- 208000020816 lung neoplasm Diseases 0.000 claims description 12
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 12
- 229960003775 miltefosine Drugs 0.000 claims description 12
- PQLXHQMOHUQAKB-UHFFFAOYSA-N miltefosine Chemical compound CCCCCCCCCCCCCCCCOP([O-])(=O)OCC[N+](C)(C)C PQLXHQMOHUQAKB-UHFFFAOYSA-N 0.000 claims description 12
- 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 12
- 201000002528 pancreatic cancer Diseases 0.000 claims description 12
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 12
- SZFPYBIJACMNJV-UHFFFAOYSA-N perifosine Chemical compound CCCCCCCCCCCCCCCCCCOP([O-])(=O)OC1CC[N+](C)(C)CC1 SZFPYBIJACMNJV-UHFFFAOYSA-N 0.000 claims description 12
- 229950010632 perifosine Drugs 0.000 claims description 12
- 238000012216 screening Methods 0.000 claims description 12
- 201000011549 stomach cancer Diseases 0.000 claims description 12
- 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
- 108091054455 MAP kinase family Proteins 0.000 claims description 10
- 102000043136 MAP kinase family Human genes 0.000 claims description 10
- 229940124647 MEK inhibitor Drugs 0.000 claims description 8
- 102100033479 RAF proto-oncogene serine/threonine-protein kinase Human genes 0.000 claims description 8
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 claims description 8
- 101000984753 Homo sapiens Serine/threonine-protein kinase B-raf Proteins 0.000 claims description 6
- 102100027103 Serine/threonine-protein kinase B-raf Human genes 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 239000002552 dosage form Substances 0.000 claims description 6
- 239000000523 sample Substances 0.000 claims description 6
- 229940126638 Akt inhibitor Drugs 0.000 claims description 4
- 239000012828 PI3K inhibitor Substances 0.000 claims description 4
- 238000003556 assay Methods 0.000 claims description 4
- 239000012472 biological sample Substances 0.000 claims description 4
- 238000012350 deep sequencing Methods 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 238000007901 in situ hybridization Methods 0.000 claims description 4
- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 claims description 4
- 239000003197 protein kinase B inhibitor Substances 0.000 claims description 4
- 238000007480 sanger sequencing Methods 0.000 claims description 4
- 238000012163 sequencing technique Methods 0.000 claims description 4
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 2
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 2
- 230000004611 cancer cell death Effects 0.000 claims description 2
- 201000000849 skin cancer Diseases 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims 3
- FPEIJQLXFHKLJV-UHFFFAOYSA-N 4-[6-(1h-indol-5-yl)-1-[1-(pyridin-3-ylmethyl)piperidin-4-yl]pyrazolo[3,4-d]pyrimidin-4-yl]morpholine Chemical compound C=1C=CN=CC=1CN(CC1)CCC1N(C1=NC(=N2)C=3C=C4C=CNC4=CC=3)N=CC1=C2N1CCOCC1 FPEIJQLXFHKLJV-UHFFFAOYSA-N 0.000 claims 1
- 101000650814 Homo sapiens Semaphorin-4C Proteins 0.000 claims 1
- 102100027745 Semaphorin-4C Human genes 0.000 claims 1
- 230000002584 immunomodulator Effects 0.000 claims 1
- 238000004806 packaging method and process Methods 0.000 claims 1
- 239000002534 radiation-sensitizing agent Substances 0.000 claims 1
- 238000001514 detection method Methods 0.000 description 4
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- 241000906446 Theraps Species 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361919638P | 2013-12-20 | 2013-12-20 | |
| US61/919,638 | 2013-12-20 | ||
| PCT/US2014/071728 WO2015095829A1 (en) | 2013-12-20 | 2014-12-19 | Cancer treatments using combinations of pi3k/akt pathway and erk inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017502014A JP2017502014A (ja) | 2017-01-19 |
| JP2017502014A5 true JP2017502014A5 (enExample) | 2018-02-08 |
| JP6727127B2 JP6727127B2 (ja) | 2020-07-29 |
Family
ID=53403792
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016540554A Active JP6727127B2 (ja) | 2013-12-20 | 2014-12-19 | Ｐｉ３ｋ／ａｋｔシグナル経路阻害剤およびｅｒｋ阻害剤の組み合わせを使用するがん処置 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US11007183B2 (enExample) |
| EP (2) | EP3082957B1 (enExample) |
| JP (1) | JP6727127B2 (enExample) |
| AU (1) | AU2014368916B2 (enExample) |
| ES (1) | ES2918375T3 (enExample) |
| WO (1) | WO2015095829A1 (enExample) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
| MX358640B (es) | 2008-01-04 | 2018-08-29 | Intellikine Llc | Isoquinolin-1 (2h) -onas y tieno [2,3-d]pirimidin-4(3h) -onas substituidas, y metodos de uso de las mismas. |
| TWI546305B (zh) | 2011-01-10 | 2016-08-21 | 英菲尼提製藥股份有限公司 | 製備異喹啉酮之方法及異喹啉酮之固體形式 |
| 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 |
| CN105102000B (zh) | 2012-11-01 | 2021-10-22 | 无限药品公司 | 使用pi3激酶亚型调节剂的癌症疗法 |
| JP2017505777A (ja) | 2014-01-29 | 2017-02-23 | シンタ ファーマスーティカルズ コーポレーション | 標的化治療薬 |
| CA2941618A1 (en) | 2014-03-03 | 2015-09-11 | Synta Pharmaceuticals Corp. | Targeted therapeutics |
| WO2015143004A1 (en) | 2014-03-18 | 2015-09-24 | Synta Pharmaceuticals Corp. | Targeted therapeutics |
| WO2015160975A2 (en) | 2014-04-16 | 2015-10-22 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| CN106333951B (zh) * | 2015-11-24 | 2018-11-02 | 中国科学院大连化学物理研究所 | 一种mTOR激酶抑制剂与MAPK激酶抑制剂的组合物的应用 |
| WO2017106492A1 (en) * | 2015-12-18 | 2017-06-22 | Ignyta, Inc. | Combinations for the treatment of cancer |
| TW201740979A (zh) * | 2016-02-29 | 2017-12-01 | 瑪德瑞高製藥公司 | 熱休克蛋白（ｈｓｐ）９０抑制劑藥物共軛物 |
| EP3474856B1 (en) | 2016-06-24 | 2022-09-14 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| MX2019013634A (es) * | 2017-05-16 | 2020-01-21 | Biomed Valley Discoveries Inc | Composiciones y metodos para tratar cancer con mutaciones de braf atipicas. |
| CN110204529A (zh) * | 2018-02-28 | 2019-09-06 | 朱允涛 | 一种氘代的三嗪类化合物的制备方法和用途 |
| WO2021219090A1 (zh) * | 2020-04-29 | 2021-11-04 | 北京泰德制药股份有限公司 | 喹喔啉二酮衍生物作为kras g12c突变蛋白的不可逆抑制剂 |
| CN113667747B (zh) * | 2020-05-14 | 2025-01-24 | 长庚大学 | 治疗口腔癌的方法 |
| KR20250057646A (ko) * | 2023-10-18 | 2025-04-29 | 주식회사 애스톤사이언스 | Kras 면역원성 펩타이드 |
| WO2025110738A1 (ko) * | 2023-11-24 | 2025-05-30 | 주식회사 캐니캐티케어 | 반려동물의 pik3ca 유전자 돌연변이성 종양 검출용 조성물 및 이를 이용한 반려동물의 pik3ca 유전자 돌연변이성 종양 진단방법 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69430909T2 (de) | 1993-03-19 | 2003-02-27 | Sequenom, Inc. | Dns-sequenzbestimmung durch massenspektrometrie auf dem weg des abbaus mit exonuklease |
| US6140053A (en) | 1996-11-06 | 2000-10-31 | Sequenom, Inc. | DNA sequencing by mass spectrometry via exonuclease degradation |
| US7439016B1 (en) | 2000-06-15 | 2008-10-21 | Digene Corporation | Detection of nucleic acids by type-specific hybrid capture method |
| US7601497B2 (en) | 2000-06-15 | 2009-10-13 | Qiagen Gaithersburg, Inc. | Detection of nucleic acids by target-specific hybrid capture method |
| GB0320059D0 (en) | 2003-08-27 | 2003-10-01 | Solexa Ltd | A method of sequencing |
| PL3305776T3 (pl) | 2004-05-14 | 2020-03-31 | Vertex Pharmaceuticals Incorporated | Związki pirolowe jako inhibitory kinaz białkowych erk i kompozycje farmaceutyczne zawierające te związki |
| US7582623B2 (en) | 2004-05-20 | 2009-09-01 | The Regents Of The University Of California | Photoactive metal nitrosyls for blood pressure regulation and cancer therapy |
| US20060228721A1 (en) | 2005-04-12 | 2006-10-12 | Leamon John H | Methods for determining sequence variants using ultra-deep sequencing |
| UA95799C2 (en) * | 2006-04-26 | 2011-09-12 | Ф. Хоффманн-Ля Рош Аг | Pharmaceutical compounds |
| TWI394839B (zh) | 2008-10-27 | 2013-05-01 | Qiagen Gaithersburg Inc | 快速結果雜交捕捉法及系統 |
| JP2013507442A (ja) * | 2009-10-12 | 2013-03-04 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー | 組合せ |
| KR20120046018A (ko) | 2010-10-04 | 2012-05-09 | 삼성테크윈 주식회사 | 단일 뉴클레오티드 다형성의 실시간 ｐｃｒ 검출 |
| WO2012068562A2 (en) * | 2010-11-19 | 2012-05-24 | The Regents Of The University Of California | Compositions and methods for detection and treatment of b-raf inhibitor-resistant melanomas |
| WO2012125848A2 (en) | 2011-03-16 | 2012-09-20 | Baylor College Of Medicine | A method for comprehensive sequence analysis using deep sequencing technology |
| PE20142020A1 (es) | 2012-04-06 | 2014-12-24 | Sanofi Sa | Metodos para tratar el cancer usando inhibidor de pi3k e inhibidor de mek |
-
2014
- 2014-12-19 US US15/105,839 patent/US11007183B2/en active Active
- 2014-12-19 EP EP14871139.3A patent/EP3082957B1/en active Active
- 2014-12-19 JP JP2016540554A patent/JP6727127B2/ja active Active
- 2014-12-19 WO PCT/US2014/071728 patent/WO2015095829A1/en not_active Ceased
- 2014-12-19 EP EP22165473.4A patent/EP4062917B1/en active Active
- 2014-12-19 ES ES14871139T patent/ES2918375T3/es active Active
- 2014-12-19 AU AU2014368916A patent/AU2014368916B2/en active Active
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2017502014A5 (enExample) | ||
| JP2017502017A5 (enExample) | ||
| Janku et al. | Targeting the PI3K pathway in cancer: are we making headway? | |
| JP6727127B2 (ja) | Ｐｉ３ｋ／ａｋｔシグナル経路阻害剤およびｅｒｋ阻害剤の組み合わせを使用するがん処置 | |
| Goldman et al. | Phase 1 dose‐escalation trial evaluating the combination of the selective MET (mesenchymal‐epithelial transition factor) inhibitor tivantinib (ARQ 197) plus erlotinib | |
| RU2016129287A (ru) | Лечение злокачественных опухолей с применением комбинаций ингибиторов erk и raf | |
| JP2017502013A5 (enExample) | ||
| Lindauer et al. | Dasatinib | |
| JP7405408B2 (ja) | 異型ｂｒａｆ変異を有するがんを処置するための組成物および方法 | |
| Fedorenko et al. | Acquired and intrinsic BRAF inhibitor resistance in BRAF V600E mutant melanoma | |
| Janku et al. | Identification of novel therapeutic targets in the PI3K/AKT/mTOR pathway in hepatocellular carcinoma using targeted next generation sequencing | |
| Wicki et al. | First-in human, phase 1, dose-escalation pharmacokinetic and pharmacodynamic study of the oral dual PI3K and mTORC1/2 inhibitor PQR309 in patients with advanced solid tumors (SAKK 67/13) | |
| Saiki et al. | MDM2 antagonists synergize broadly and robustly with compounds targeting fundamental oncogenic signaling pathways | |
| JP2022034068A (ja) | 非ｅｒｋ ｍａｐｋ経路阻害剤耐性のがんを処置するための方法および組成物 | |
| Imura et al. | Combined targeting of mTOR and c-MET signaling pathways for effective management of epithelioid sarcoma | |
| JP2017502016A5 (enExample) | ||
| Leung et al. | Potentiation of growth inhibitory responses of the mTOR inhibitor everolimus by dual mTORC1/2 inhibitors in cultured breast cancer cell lines | |
| D’Cruz et al. | Novel Bruton’s tyrosine kinase inhibitors currently in development | |
| Wells Jr et al. | Update: the status of clinical trials with kinase inhibitors in thyroid cancer | |
| Bailey et al. | mTOR inhibition induces compensatory, therapeutically targetable MEK activation in renal cell carcinoma | |
| CN105451750A (zh) | 治疗人的实体肿瘤的诺氏梭菌 | |
| EP3503922B1 (en) | Combination therapy for the treatment of pancreatic cancer | |
| Davis et al. | Combined inhibition of MEK and Aurora A kinase in KRAS/PIK3CA double-mutant colorectal cancer models | |
| KR20230015888A (ko) | 사시투주맙 고비테칸 요법에 대한 바이오마커 | |
| Viktorsson et al. | Advances in molecular targeted therapies to increase efficacy of (chemo) radiation therapy |