CA2736361C - Combination of a phosphatidylinositol-3-kinase (pi3k) inhibitor and a mtor inhibitor - Google Patents
Combination of a phosphatidylinositol-3-kinase (pi3k) inhibitor and a mtor inhibitor Download PDFInfo
- Publication number
- CA2736361C CA2736361C CA2736361A CA2736361A CA2736361C CA 2736361 C CA2736361 C CA 2736361C CA 2736361 A CA2736361 A CA 2736361A CA 2736361 A CA2736361 A CA 2736361A CA 2736361 C CA2736361 C CA 2736361C
- Authority
- CA
- Canada
- Prior art keywords
- treatment
- pharmaceutically acceptable
- acceptable salt
- mtor
- combination
- 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.)
- Expired - Fee Related
Links
- 229940124302 mTOR inhibitor Drugs 0.000 title claims abstract description 37
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 title claims abstract description 37
- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 title abstract description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 36
- 201000010099 disease Diseases 0.000 claims abstract description 34
- 230000002062 proliferating effect Effects 0.000 claims abstract description 23
- 230000001419 dependent effect Effects 0.000 claims abstract description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
- 108091000080 Phosphotransferase Proteins 0.000 claims abstract description 11
- 102000020233 phosphotransferase Human genes 0.000 claims abstract description 11
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 9
- 239000003814 drug Substances 0.000 claims abstract description 6
- 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 23
- 150000003839 salts Chemical class 0.000 claims description 20
- 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 20
- 229960005167 everolimus Drugs 0.000 claims description 18
- 229960002930 sirolimus Drugs 0.000 claims description 17
- 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 11
- 206010006187 Breast cancer Diseases 0.000 claims description 10
- 208000026310 Breast neoplasm Diseases 0.000 claims description 10
- 230000004913 activation Effects 0.000 claims description 9
- 230000026731 phosphorylation Effects 0.000 claims description 8
- 238000006366 phosphorylation reaction Methods 0.000 claims description 8
- 206010061968 Gastric neoplasm Diseases 0.000 claims description 7
- 206010025323 Lymphomas Diseases 0.000 claims description 7
- 230000002265 prevention Effects 0.000 claims description 7
- 206010060862 Prostate cancer Diseases 0.000 claims description 6
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 6
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 6
- 230000003247 decreasing effect Effects 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 230000035945 sensitivity Effects 0.000 claims description 3
- CWHUFRVAEUJCEF-UHFFFAOYSA-N BKM120 Chemical compound C1=NC(N)=CC(C(F)(F)F)=C1C1=CC(N2CCOCC2)=NC(N2CCOCC2)=N1 CWHUFRVAEUJCEF-UHFFFAOYSA-N 0.000 claims 5
- 206010052399 Neuroendocrine tumour Diseases 0.000 claims 4
- 208000016065 neuroendocrine neoplasm Diseases 0.000 claims 4
- 201000011519 neuroendocrine tumor Diseases 0.000 claims 4
- 150000001875 compounds Chemical class 0.000 abstract description 43
- 238000000034 method Methods 0.000 abstract description 15
- 241001465754 Metazoa Species 0.000 abstract description 10
- 238000002360 preparation method Methods 0.000 abstract description 4
- 201000011510 cancer Diseases 0.000 abstract description 3
- 239000002935 phosphatidylinositol 3 kinase inhibitor Substances 0.000 abstract 1
- 239000004480 active ingredient Substances 0.000 description 13
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 12
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 12
- 239000012828 PI3K inhibitor Substances 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 9
- 229910052739 hydrogen Inorganic materials 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- -1 SAR543 Chemical compound 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 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 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 125000004093 cyano group Chemical group *C#N 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 229960000235 temsirolimus Drugs 0.000 description 4
- 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 description 3
- ZDQSOHOQTUFQEM-PKUCKEGBSA-N ascomycin Chemical compound C/C([C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H]([C@H](C[C@H]2C)OC)[C@@H](OC)C[C@@H](C)C\C(C)=C/[C@H](C(C[C@H](O)[C@H]1C)=O)CC)=C\[C@@H]1CC[C@@H](O)[C@H](OC)C1 ZDQSOHOQTUFQEM-PKUCKEGBSA-N 0.000 description 3
- ZDQSOHOQTUFQEM-XCXYXIJFSA-N ascomycin Natural products CC[C@H]1C=C(C)C[C@@H](C)C[C@@H](OC)[C@H]2O[C@@](O)([C@@H](C)C[C@H]2OC)C(=O)C(=O)N3CCCC[C@@H]3C(=O)O[C@H]([C@H](C)[C@@H](O)CC1=O)C(=C[C@@H]4CC[C@@H](O)[C@H](C4)OC)C ZDQSOHOQTUFQEM-XCXYXIJFSA-N 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- JROFGZPOBKIAEW-UHFFFAOYSA-N chembl2132692 Chemical compound N1C=2C(OC)=CC=CC=2C=C1C(=C1C(N)=NC=NN11)N=C1C1CCC(C(O)=O)CC1 JROFGZPOBKIAEW-UHFFFAOYSA-N 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 125000001072 heteroaryl group Chemical group 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- 229920000136 polysorbate Polymers 0.000 description 3
- 150000003230 pyrimidines Chemical class 0.000 description 3
- 229950009216 sapanisertib Drugs 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 229950009819 zotarolimus Drugs 0.000 description 3
- 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 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- 229930182816 L-glutamine Natural products 0.000 description 2
- 108010006877 Tacrolimus Binding Protein 1A Proteins 0.000 description 2
- 206010052779 Transplant rejections Diseases 0.000 description 2
- 206010064930 age-related macular degeneration Diseases 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 201000008275 breast carcinoma Diseases 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 238000001378 electrochemiluminescence detection Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 230000009826 neoplastic cell growth Effects 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 2
- 238000009097 single-agent therapy Methods 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 208000031277 Amaurotic familial idiocy Diseases 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 238000000035 BCA protein assay Methods 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 206010006895 Cachexia Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 201000005947 Carney Complex Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 208000011518 Danon disease Diseases 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- 208000008069 Geographic Atrophy Diseases 0.000 description 1
- 208000001500 Glycogen Storage Disease Type IIb Diseases 0.000 description 1
- 208000035148 Glycogen storage disease due to LAMP-2 deficiency Diseases 0.000 description 1
- 206010053185 Glycogen storage disease type II Diseases 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 208000031309 Hypertrophic Familial Cardiomyopathy Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 description 1
- 101710184277 Insulin-like growth factor 1 receptor Proteins 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 206010049459 Lymphangioleiomyomatosis Diseases 0.000 description 1
- 208000002569 Machado-Joseph Disease Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000026072 Motor neurone disease Diseases 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 201000009623 Myopathy Diseases 0.000 description 1
- 208000033793 Neuroendocrine tumor of stomach Diseases 0.000 description 1
- 208000009905 Neurofibromatoses Diseases 0.000 description 1
- 208000003019 Neurofibromatosis 1 Diseases 0.000 description 1
- 208000024834 Neurofibromatosis type 1 Diseases 0.000 description 1
- 208000002537 Neuronal Ceroid-Lipofuscinoses Diseases 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 102100027913 Peptidyl-prolyl cis-trans isomerase FKBP1A Human genes 0.000 description 1
- 206010034764 Peutz-Jeghers syndrome Diseases 0.000 description 1
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 1
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 206010038910 Retinitis Diseases 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 208000036834 Spinocerebellar ataxia type 3 Diseases 0.000 description 1
- 241001505901 Streptococcus sp. 'group A' Species 0.000 description 1
- 102000008221 Superoxide Dismutase-1 Human genes 0.000 description 1
- 108010021188 Superoxide Dismutase-1 Proteins 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N THREONINE Chemical compound CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 108010027179 Tacrolimus Binding Proteins Proteins 0.000 description 1
- 102000018679 Tacrolimus Binding Proteins Human genes 0.000 description 1
- 208000026911 Tuberous sclerosis complex Diseases 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 208000000208 Wet Macular Degeneration Diseases 0.000 description 1
- 201000008803 Wolff-Parkinson-white syndrome Diseases 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 208000037844 advanced solid tumor Diseases 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 201000002758 colorectal adenoma Diseases 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 201000001981 dermatomyositis Diseases 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 201000002491 encephalomyelitis Diseases 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 201000006692 familial hypertrophic cardiomyopathy Diseases 0.000 description 1
- 230000003176 fibrotic effect Effects 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 201000011587 gastric lymphoma Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 239000012135 ice-cold extraction buffer Substances 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 208000017476 juvenile neuronal ceroid lipofuscinosis Diseases 0.000 description 1
- 201000008632 juvenile polyposis syndrome Diseases 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 208000005264 motor neuron disease Diseases 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 201000000585 muscular atrophy Diseases 0.000 description 1
- 208000025440 neoplasm of neck Diseases 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 201000004931 neurofibromatosis Diseases 0.000 description 1
- 201000007607 neuronal ceroid lipofuscinosis 3 Diseases 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 208000015768 polyposis Diseases 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 229940099538 rapamune Drugs 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 201000002793 renal fibrosis Diseases 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- QFMKPDZCOKCBAQ-NFCVMBANSA-N sar943-nxa 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)CC1 QFMKPDZCOKCBAQ-NFCVMBANSA-N 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 235000015393 sodium molybdate Nutrition 0.000 description 1
- 239000011684 sodium molybdate Substances 0.000 description 1
- TVXXNOYZHKPKGW-UHFFFAOYSA-N sodium molybdate (anhydrous) Chemical compound [Na+].[Na+].[O-][Mo]([O-])(=O)=O TVXXNOYZHKPKGW-UHFFFAOYSA-N 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 208000009999 tuberous sclerosis Diseases 0.000 description 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 208000006542 von Hippel-Lindau disease Diseases 0.000 description 1
- 208000036506 well differentiated low or intermediate grade gastric neuroendocrine tumor Diseases 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- 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
- A61K31/436—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 six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Neurology (AREA)
- Cardiology (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Physical Education & Sports Medicine (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Dermatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Communicable Diseases (AREA)
- Psychology (AREA)
- Ophthalmology & Optometry (AREA)
- Psychiatry (AREA)
- Virology (AREA)
- Hematology (AREA)
- Rheumatology (AREA)
- Transplantation (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP08168044 | 2008-10-31 | ||
| EP08168044.9 | 2008-10-31 | ||
| PCT/EP2009/064274 WO2010049481A1 (en) | 2008-10-31 | 2009-10-29 | Combination of a phosphatidylinositol-3-kinase (pi3k) inhibitor and a mtor inhibitor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2736361A1 CA2736361A1 (en) | 2010-05-06 |
| CA2736361C true CA2736361C (en) | 2017-10-10 |
Family
ID=40332588
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2736361A Expired - Fee Related CA2736361C (en) | 2008-10-31 | 2009-10-29 | Combination of a phosphatidylinositol-3-kinase (pi3k) inhibitor and a mtor inhibitor |
Country Status (12)
| Country | Link |
|---|---|
| US (3) | US20110195966A1 (cg-RX-API-DMAC7.html) |
| EP (1) | EP2349275B1 (cg-RX-API-DMAC7.html) |
| JP (4) | JP2012506898A (cg-RX-API-DMAC7.html) |
| KR (1) | KR20110090911A (cg-RX-API-DMAC7.html) |
| CN (2) | CN102202668A (cg-RX-API-DMAC7.html) |
| AU (1) | AU2009309616B2 (cg-RX-API-DMAC7.html) |
| BR (1) | BRPI0921802A8 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2736361C (cg-RX-API-DMAC7.html) |
| ES (1) | ES2627677T3 (cg-RX-API-DMAC7.html) |
| MX (1) | MX2011004585A (cg-RX-API-DMAC7.html) |
| RU (2) | RU2538683C2 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2010049481A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100048914A1 (en) | 2008-03-14 | 2010-02-25 | Angela Brodie | Novel C-17-Heteroaryl Steroidal Cyp17 Inhibitors/Antiandrogens, In Vitro Biological Activities, Pharmacokinetics and Antitumor Activity |
| US8476431B2 (en) * | 2008-11-03 | 2013-07-02 | Itellikine LLC | Benzoxazole kinase inhibitors and methods of use |
| WO2010056754A2 (en) | 2008-11-11 | 2010-05-20 | The Board Regents Of The University Of Texas System | Inhibition of mammalian target of rapamycin |
| BRPI1008745A2 (pt) | 2009-02-05 | 2019-09-17 | Tokai Pharmaceuticals Inc | pró-fármacos de inibidores esteroidais de cyp17/antiandrogênios |
| US9283211B1 (en) | 2009-11-11 | 2016-03-15 | Rapamycin Holdings, Llc | Oral rapamycin preparation and use for stomatitis |
| US10391059B2 (en) | 2009-11-11 | 2019-08-27 | Rapamycin Holdings, Inc. | Oral rapamycin nanoparticle preparations and use |
| GB2478556A (en) * | 2010-03-09 | 2011-09-14 | Myrovlytis Technology Ventures Ltd | A composition for use in the treatment of Birt-Hogg-Dubô sydrome |
| ES2570183T3 (es) * | 2011-02-16 | 2016-05-17 | Novartis Ag | Combinaciones de agentes terapéuticos para uso en el tratamiento de enfermedades neurodegenerativas |
| CN106619647A (zh) * | 2011-02-23 | 2017-05-10 | 因特利凯有限责任公司 | 激酶抑制剂的组合及其用途 |
| BR112013022697A2 (pt) * | 2011-03-07 | 2019-09-24 | Fond Telethon | inibidores de fosforilação de tfeb e usos dos mesmos |
| NZ615593A (en) * | 2011-04-25 | 2015-05-29 | Novartis Ag | Combination of a phosphatidylinositol-3-kinase (pi3k) inhibitor and a mtor inhibitor |
| EP2705181B1 (en) * | 2011-05-04 | 2016-12-21 | Intellikine, LLC | Combination pharmaceutical compositions and uses thereof |
| EP2771337B1 (en) | 2011-09-27 | 2017-08-02 | Novartis AG | 3-(pyrimidin-4-yl)-oxazolidin-2-ones as inhibitors of mutant idh |
| CN106924741A (zh) * | 2011-11-08 | 2017-07-07 | 因特利凯有限责任公司 | 使用多种药剂的治疗方案 |
| CN104363914A (zh) | 2011-11-23 | 2015-02-18 | 因特利凯有限责任公司 | 使用mTOR抑制剂的增强的治疗方案 |
| UY34632A (es) * | 2012-02-24 | 2013-05-31 | Novartis Ag | Compuestos de oxazolidin- 2- ona y usos de los mismos |
| RU2012112128A (ru) * | 2012-03-29 | 2013-10-10 | Холин Максим Николаевич | ИНГИБИТОРЫ СИГНАЛЬНОГО ПУТИ PI3K/AKT/IKK/NF-kB, ИХ ФАРМАЦЕВТИЧЕСКИ ПРИЕМЛЕМЫЕ СОЛИ И СОДЕРЖАЩИЕ ИХ КОМПОЗИЦИИ ДЛЯ ПРОФИЛАКТИКИ И ЛЕЧЕНИЯ ВИРУСНЫХ ЗАБОЛЕВАНИЙ |
| US9296733B2 (en) | 2012-11-12 | 2016-03-29 | Novartis Ag | Oxazolidin-2-one-pyrimidine derivative and use thereof for the treatment of conditions, diseases and disorders dependent upon PI3 kinases |
| WO2014160328A1 (en) | 2013-03-13 | 2014-10-02 | The Board Of Regents Of The University Of Texas System | Mtor inhibitors for prevention of intestinal polyp growth |
| CN105682662A (zh) | 2013-03-14 | 2016-06-15 | 马里兰大学巴尔的摩校区 | 雄激素受体减量调节剂及其用途 |
| AU2014229313B2 (en) | 2013-03-14 | 2016-07-28 | Novartis Ag | 3-pyrimidin-4-yl-oxazolidin-2-ones as inhibitors of mutant IDH |
| MX2015011899A (es) | 2013-03-15 | 2016-05-05 | Genentech Inc | Metodos para el tratamiento de cáncer y prevención de resistencia a los fármacos para el cáncer. |
| CR20200177A (es) | 2013-05-01 | 2020-06-28 | Hoffmann La Roche | Compuestos de biheteroarilo (divisional 2015-0589) |
| BR112016002970A2 (pt) | 2013-08-12 | 2017-09-12 | Tokai Pharmaceuticals Inc | biomarcadores para o tratamento de distúrbios neoplásicos que usa terapias direcionadas ao androgênio |
| CN103483345B (zh) * | 2013-09-25 | 2016-07-06 | 中山大学 | Pi3k激酶抑制剂、包含其的药物组合物及其应用 |
| US9700544B2 (en) | 2013-12-31 | 2017-07-11 | Neal K Vail | Oral rapamycin nanoparticle preparations |
| EP3708680B8 (en) | 2015-04-15 | 2023-08-30 | University of Massachusetts | Compositions and methods for xi chromosome reactivation |
| US10576076B2 (en) | 2015-05-20 | 2020-03-03 | Novartis Ag | Pharmaceutical combination of everolimus with dactolisib |
| US10441584B2 (en) | 2016-11-23 | 2019-10-15 | Novartis Ag | Methods of enhancing immune response |
| US10596165B2 (en) | 2018-02-12 | 2020-03-24 | resTORbio, Inc. | Combination therapies |
| KR20210158019A (ko) | 2020-06-23 | 2021-12-30 | 주식회사 온코빅스 | 포스파티딜이노시톨 3-키나제(pi3k) 억제제로써 pten 과오종 증후군에 의한 종양 세포의 성장 또는 증식을 억제하는데 유용한 신규한 피리미딘 유도체 및 이의 약제학적으로 허용가능한 염, 및 이를 유효성분으로 함유하는 약제학적 조성물 |
| CN112294967A (zh) * | 2020-09-30 | 2021-02-02 | 四川大学 | 一种mTOR抑制剂与抗癌药物的用途 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL153474A0 (en) * | 2000-06-26 | 2003-07-06 | Stressgen Biotechnologies Corp | Human papilloma virus treatment |
| BRPI0516592A (pt) * | 2004-10-13 | 2008-09-23 | Wyeth Corp | composto de fórmula |
| US20080200486A1 (en) * | 2005-07-20 | 2008-08-21 | Heidi Lane | Combination Of Organic Compounds |
| CA2628920C (en) * | 2005-11-22 | 2015-12-29 | Kudos Pharmaceuticals Limited | Pyrido-,pyrazo- and pyrimido-pyrimidine derivatives as mtor inhibitors |
| JO2660B1 (en) * | 2006-01-20 | 2012-06-17 | نوفارتيس ايه جي | Pi-3 inhibitors and methods of use |
| WO2007087395A2 (en) * | 2006-01-25 | 2007-08-02 | Osi Pharmaceuticals, Inc. | UNSATURATED mTOR INHIBITORS |
| WO2007120897A2 (en) * | 2006-04-13 | 2007-10-25 | The Trustees Of Columbia University In The City Of New York | Compositions and intraluminal devices for inhibiting vascular stenosis |
| KR20090108124A (ko) * | 2007-02-06 | 2009-10-14 | 노파르티스 아게 | Ｐｉ 3-키나제 억제제 및 그의 사용 방법 |
| WO2008103636A1 (en) * | 2007-02-20 | 2008-08-28 | Novartis Ag | Imidazoquinolines as dual lipid kinase and mtor inhibitors |
| EP2231147A2 (en) * | 2007-12-13 | 2010-09-29 | Novartis AG | Combinations of therapeutic agents for treating cancer |
-
2009
- 2009-10-29 US US13/123,956 patent/US20110195966A1/en not_active Abandoned
- 2009-10-29 WO PCT/EP2009/064274 patent/WO2010049481A1/en not_active Ceased
- 2009-10-29 CN CN2009801431736A patent/CN102202668A/zh active Pending
- 2009-10-29 KR KR1020117009771A patent/KR20110090911A/ko not_active Ceased
- 2009-10-29 EP EP09744391.5A patent/EP2349275B1/en not_active Not-in-force
- 2009-10-29 MX MX2011004585A patent/MX2011004585A/es active IP Right Grant
- 2009-10-29 AU AU2009309616A patent/AU2009309616B2/en not_active Ceased
- 2009-10-29 ES ES09744391.5T patent/ES2627677T3/es active Active
- 2009-10-29 CA CA2736361A patent/CA2736361C/en not_active Expired - Fee Related
- 2009-10-29 BR BRPI0921802A patent/BRPI0921802A8/pt not_active IP Right Cessation
- 2009-10-29 JP JP2011533721A patent/JP2012506898A/ja not_active Withdrawn
- 2009-10-29 RU RU2011121508/15A patent/RU2538683C2/ru not_active IP Right Cessation
- 2009-10-29 CN CN201510402018.9A patent/CN105030784A/zh active Pending
-
2014
- 2014-04-15 RU RU2014115188/15A patent/RU2014115188A/ru not_active Application Discontinuation
- 2014-09-05 JP JP2014181069A patent/JP2015013883A/ja not_active Withdrawn
-
2015
- 2015-11-24 US US14/950,869 patent/US20160136175A1/en not_active Abandoned
-
2016
- 2016-07-06 JP JP2016134514A patent/JP2017002058A/ja not_active Ceased
-
2018
- 2018-01-16 US US15/872,043 patent/US20180133226A1/en not_active Abandoned
- 2018-07-20 JP JP2018136756A patent/JP2018197243A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN102202668A (zh) | 2011-09-28 |
| RU2014115188A (ru) | 2015-10-20 |
| RU2011121508A (ru) | 2012-12-10 |
| EP2349275B1 (en) | 2017-03-08 |
| BRPI0921802A8 (pt) | 2018-03-13 |
| JP2018197243A (ja) | 2018-12-13 |
| JP2015013883A (ja) | 2015-01-22 |
| EP2349275A1 (en) | 2011-08-03 |
| AU2009309616A2 (en) | 2011-07-07 |
| AU2009309616B2 (en) | 2014-02-13 |
| US20110195966A1 (en) | 2011-08-11 |
| JP2017002058A (ja) | 2017-01-05 |
| RU2538683C2 (ru) | 2015-01-10 |
| KR20110090911A (ko) | 2011-08-10 |
| US20180133226A1 (en) | 2018-05-17 |
| ES2627677T3 (es) | 2017-07-31 |
| CA2736361A1 (en) | 2010-05-06 |
| US20160136175A1 (en) | 2016-05-19 |
| CN105030784A (zh) | 2015-11-11 |
| BRPI0921802A2 (pt) | 2016-09-27 |
| MX2011004585A (es) | 2011-06-01 |
| AU2009309616A1 (en) | 2010-05-06 |
| JP2012506898A (ja) | 2012-03-22 |
| WO2010049481A1 (en) | 2010-05-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2736361C (en) | Combination of a phosphatidylinositol-3-kinase (pi3k) inhibitor and a mtor inhibitor | |
| HUE031367T2 (en) | A pharmaceutical combination comprising an Hsp 90 inhibitor and a mTOR inhibitor | |
| AU2016202372B2 (en) | Combination of a phosphatidylinositol-3-kinase (PI3K) inhibitor and a mTOR inhibitor | |
| AU2008202690A1 (en) | Antineoplastic combination | |
| AU2005312061B2 (en) | Combinations comprising epothilones and protein tyrosine kinase inhibitors and pharmaceutical uses thereof | |
| CN102834094B (zh) | 有机化合物的组合产品及其制药用途 | |
| KR20130087058A (ko) | 피리미딜아미노벤즈아미드와 ｍｔｏｒ 키나제 억제제의 조합물 | |
| HK1226654A1 (en) | Anti-tumor activity of temsirolimus in papillary renal cell cancer | |
| HK1226654A (en) | Anti-tumor activity of temsirolimus in papillary renal cell cancer | |
| HK1142538A (en) | Anti-tumor activity of temsirolimus in papillary renal cell cancer |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20141023 |
|
| MKLA | Lapsed |
Effective date: 20201029 |