CN105030784A - 磷脂酰肌醇-3-激酶(PI3K)抑制剂和mTOR抑制剂的组合产品 - Google Patents
磷脂酰肌醇-3-激酶(PI3K)抑制剂和mTOR抑制剂的组合产品 Download PDFInfo
- Publication number
- CN105030784A CN105030784A CN201510402018.9A CN201510402018A CN105030784A CN 105030784 A CN105030784 A CN 105030784A CN 201510402018 A CN201510402018 A CN 201510402018A CN 105030784 A CN105030784 A CN 105030784A
- Authority
- CN
- China
- Prior art keywords
- carcinoma
- cancer
- mtor
- kinase
- compound
- 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
- 229940124302 mTOR inhibitor Drugs 0.000 title abstract description 32
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 title abstract description 32
- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 title abstract description 18
- 150000001875 compounds Chemical class 0.000 claims abstract description 49
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 32
- 201000010099 disease Diseases 0.000 claims abstract description 31
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 13
- 108091000080 Phosphotransferase Proteins 0.000 claims abstract description 9
- 102000020233 phosphotransferase Human genes 0.000 claims abstract description 9
- 201000011510 cancer Diseases 0.000 claims abstract description 8
- 230000001419 dependent effect Effects 0.000 claims abstract description 8
- 239000003814 drug Substances 0.000 claims abstract description 6
- 239000013066 combination product Substances 0.000 claims description 24
- 229940127555 combination product Drugs 0.000 claims description 24
- 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 22
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 claims description 19
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 claims description 19
- 229960005167 everolimus Drugs 0.000 claims description 16
- 150000001412 amines Chemical class 0.000 claims description 11
- 206010006187 Breast cancer Diseases 0.000 claims description 10
- 208000026310 Breast neoplasm Diseases 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 8
- 201000008275 breast carcinoma Diseases 0.000 claims description 6
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 5
- 206010061968 Gastric neoplasm Diseases 0.000 claims description 4
- 230000009826 neoplastic cell growth Effects 0.000 claims description 4
- 201000001514 prostate carcinoma Diseases 0.000 claims description 4
- 206010009944 Colon cancer Diseases 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 206010005003 Bladder cancer Diseases 0.000 claims description 2
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 2
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 claims description 2
- 201000010915 Glioblastoma multiforme Diseases 0.000 claims description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
- 206010025323 Lymphomas Diseases 0.000 claims description 2
- 208000034578 Multiple myelomas Diseases 0.000 claims description 2
- 208000033793 Neuroendocrine tumor of stomach Diseases 0.000 claims description 2
- 206010033128 Ovarian cancer Diseases 0.000 claims description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 2
- 206010038389 Renal cancer Diseases 0.000 claims description 2
- 206010039491 Sarcoma Diseases 0.000 claims description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
- 208000033781 Thyroid carcinoma Diseases 0.000 claims description 2
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 2
- 201000005179 adrenal carcinoma Diseases 0.000 claims description 2
- 201000005188 adrenal gland cancer Diseases 0.000 claims description 2
- 210000001072 colon Anatomy 0.000 claims description 2
- 206010017758 gastric cancer Diseases 0.000 claims description 2
- 208000005017 glioblastoma Diseases 0.000 claims description 2
- 208000032839 leukemia Diseases 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
- 201000001475 prostate lymphoma Diseases 0.000 claims description 2
- 208000020615 rectal carcinoma Diseases 0.000 claims description 2
- 201000010174 renal carcinoma Diseases 0.000 claims description 2
- 201000011549 stomach cancer Diseases 0.000 claims description 2
- 201000002510 thyroid cancer Diseases 0.000 claims description 2
- 208000013077 thyroid gland carcinoma Diseases 0.000 claims description 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 2
- 206010046885 vaginal cancer Diseases 0.000 claims description 2
- 208000013139 vaginal neoplasm Diseases 0.000 claims description 2
- 208000036506 well differentiated low or intermediate grade gastric neuroendocrine tumor Diseases 0.000 claims description 2
- 206010052399 Neuroendocrine tumour Diseases 0.000 claims 1
- 208000016065 neuroendocrine neoplasm Diseases 0.000 claims 1
- 201000011519 neuroendocrine tumor Diseases 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 30
- 230000002062 proliferating effect Effects 0.000 abstract description 21
- 241001465754 Metazoa Species 0.000 abstract description 10
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 9
- 238000002360 preparation method Methods 0.000 abstract description 6
- 239000002935 phosphatidylinositol 3 kinase inhibitor Substances 0.000 abstract 1
- 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 description 19
- 239000012828 PI3K inhibitor Substances 0.000 description 13
- 230000003213 activating effect Effects 0.000 description 13
- 230000000694 effects Effects 0.000 description 12
- 229960002930 sirolimus Drugs 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 11
- 229910052739 hydrogen Inorganic materials 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 230000026731 phosphorylation Effects 0.000 description 9
- 238000006366 phosphorylation reaction Methods 0.000 description 9
- 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 description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- -1 AP23841 Chemical compound 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- 241001597008 Nomeidae Species 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 5
- 230000004913 activation Effects 0.000 description 5
- 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
- 230000008569 process Effects 0.000 description 5
- 229960000235 temsirolimus Drugs 0.000 description 5
- 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 5
- 229950009819 zotarolimus Drugs 0.000 description 5
- 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 4
- 206010059866 Drug resistance Diseases 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 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 4
- 125000004093 cyano group Chemical group *C#N 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- 125000001072 heteroaryl group Chemical group 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 229950009216 sapanisertib Drugs 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 230000000968 intestinal effect Effects 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 206010002027 Amyotrophy Diseases 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
- DHCLVCXQIBBOPH-UHFFFAOYSA-N Glycerol 2-phosphate Chemical compound OCC(CO)OP(O)(O)=O DHCLVCXQIBBOPH-UHFFFAOYSA-N 0.000 description 2
- 208000009905 Neurofibromatoses Diseases 0.000 description 2
- 208000002537 Neuronal Ceroid-Lipofuscinoses Diseases 0.000 description 2
- 102000004584 Somatomedin Receptors Human genes 0.000 description 2
- 108010017622 Somatomedin Receptors Proteins 0.000 description 2
- 206010052779 Transplant rejections Diseases 0.000 description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 238000011262 co‐therapy Methods 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 201000004931 neurofibromatosis Diseases 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 150000003230 pyrimidines Chemical class 0.000 description 2
- 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 2
- 230000035945 sensitivity Effects 0.000 description 2
- 238000007086 side reaction Methods 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
- 230000001629 suppression Effects 0.000 description 2
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 2
- 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
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 238000000035 BCA protein assay Methods 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- 206010006895 Cachexia Diseases 0.000 description 1
- 201000005947 Carney Complex Diseases 0.000 description 1
- 206010052360 Colorectal adenocarcinoma Diseases 0.000 description 1
- 208000012609 Cowden disease Diseases 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 201000006107 Familial adenomatous polyposis Diseases 0.000 description 1
- 208000008069 Geographic Atrophy Diseases 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 208000002927 Hamartoma Diseases 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 208000031309 Hypertrophic Familial Cardiomyopathy Diseases 0.000 description 1
- 108060003951 Immunoglobulin 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
- 208000002569 Machado-Joseph Disease Diseases 0.000 description 1
- 208000026072 Motor neurone disease Diseases 0.000 description 1
- 208000008770 Multiple Hamartoma Syndrome Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- 201000009623 Myopathy Diseases 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 208000018737 Parkinson disease Diseases 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
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 1
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 208000007014 Retinitis pigmentosa Diseases 0.000 description 1
- 208000025747 Rheumatic disease 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
- 241000187391 Streptomyces hygroscopicus Species 0.000 description 1
- 102000008221 Superoxide Dismutase-1 Human genes 0.000 description 1
- 108010021188 Superoxide Dismutase-1 Proteins 0.000 description 1
- 108010006877 Tacrolimus Binding Protein 1A Proteins 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 208000026911 Tuberous sclerosis complex Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 208000037844 advanced solid tumor Diseases 0.000 description 1
- 206010064930 age-related macular degeneration Diseases 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000000035 biogenic effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000002612 cardiopulmonary effect Effects 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
- 238000005352 clarification Methods 0.000 description 1
- 208000029664 classic familial adenomatous polyposis Diseases 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 239000000470 constituent Substances 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
- 230000005750 disease progression Effects 0.000 description 1
- 238000001378 electrochemiluminescence detection Methods 0.000 description 1
- 201000002491 encephalomyelitis Diseases 0.000 description 1
- 150000002148 esters Chemical class 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
- 239000003205 fragrance Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000003463 hyperproliferative effect Effects 0.000 description 1
- 239000012135 ice-cold extraction buffer Substances 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 102000018358 immunoglobulin Human genes 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
- 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
- 238000011081 inoculation Methods 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 208000017476 juvenile neuronal ceroid lipofuscinosis Diseases 0.000 description 1
- 201000008632 juvenile polyposis syndrome Diseases 0.000 description 1
- 150000003951 lactams Chemical class 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
- 210000004185 liver Anatomy 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 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
- 230000001537 neural effect Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 201000008051 neuronal ceroid lipofuscinosis Diseases 0.000 description 1
- 201000007607 neuronal ceroid lipofuscinosis 3 Diseases 0.000 description 1
- 210000000056 organ 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
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000047 product Substances 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
- 230000009467 reduction Effects 0.000 description 1
- 201000002793 renal fibrosis Diseases 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000003491 skin Anatomy 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
- 229960005322 streptomycin Drugs 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
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000002054 transplantation Methods 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
- 208000009999 tuberous sclerosis Diseases 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 208000006542 von Hippel-Lindau disease Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000003313 weakening effect Effects 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)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Cardiology (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Oncology (AREA)
- Physical Education & Sports Medicine (AREA)
- Communicable Diseases (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Psychology (AREA)
- Dermatology (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Transplantation (AREA)
- Psychiatry (AREA)
- Urology & Nephrology (AREA)
- Virology (AREA)
- Rheumatology (AREA)
- Vascular Medicine (AREA)
- Pulmonology (AREA)
- Ophthalmology & Optometry (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP08168044.9 | 2008-10-31 | ||
| EP08168044 | 2008-10-31 | ||
| CN2009801431736A CN102202668A (zh) | 2008-10-31 | 2009-10-29 | 磷脂酰肌醇-3-激酶(PI3K)抑制剂和mTOR抑制剂的组合产品 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009801431736A Division CN102202668A (zh) | 2008-10-31 | 2009-10-29 | 磷脂酰肌醇-3-激酶(PI3K)抑制剂和mTOR抑制剂的组合产品 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105030784A true CN105030784A (zh) | 2015-11-11 |
Family
ID=40332588
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510402018.9A Pending CN105030784A (zh) | 2008-10-31 | 2009-10-29 | 磷脂酰肌醇-3-激酶(PI3K)抑制剂和mTOR抑制剂的组合产品 |
| CN2009801431736A Pending CN102202668A (zh) | 2008-10-31 | 2009-10-29 | 磷脂酰肌醇-3-激酶(PI3K)抑制剂和mTOR抑制剂的组合产品 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009801431736A Pending CN102202668A (zh) | 2008-10-31 | 2009-10-29 | 磷脂酰肌醇-3-激酶(PI3K)抑制剂和mTOR抑制剂的组合产品 |
Country Status (12)
| Country | Link |
|---|---|
| US (3) | US20110195966A1 (enExample) |
| EP (1) | EP2349275B1 (enExample) |
| JP (4) | JP2012506898A (enExample) |
| KR (1) | KR20110090911A (enExample) |
| CN (2) | CN105030784A (enExample) |
| AU (1) | AU2009309616B2 (enExample) |
| BR (1) | BRPI0921802A8 (enExample) |
| CA (1) | CA2736361C (enExample) |
| ES (1) | ES2627677T3 (enExample) |
| MX (1) | MX2011004585A (enExample) |
| RU (2) | RU2538683C2 (enExample) |
| WO (1) | WO2010049481A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100048913A1 (en) | 2008-03-14 | 2010-02-25 | Angela Brodie | Novel C-17-Heteroaryl Steroidal CYP17 Inhibitors/Antiandrogens;Synthesis In Vitro Biological Activities, Pharmacokinetics and Antitumor Activity |
| US8476282B2 (en) * | 2008-11-03 | 2013-07-02 | Intellikine Llc | Benzoxazole kinase inhibitors and methods of use |
| CN102292078A (zh) | 2008-11-11 | 2011-12-21 | 得克萨斯大学体系董事会 | 哺乳动物雷帕霉素靶蛋白的抑制 |
| EP2393827B1 (en) | 2009-02-05 | 2015-10-07 | Tokai Pharmaceuticals, Inc. | Novel prodrugs of steroidal cyp17 inhibitors/antiandrogens |
| US9283211B1 (en) | 2009-11-11 | 2016-03-15 | Rapamycin Holdings, Llc | Oral rapamycin preparation and use for stomatitis |
| GB2478556A (en) * | 2010-03-09 | 2011-09-14 | Myrovlytis Technology Ventures Ltd | A composition for use in the treatment of Birt-Hogg-Dubô sydrome |
| CN103391780B (zh) * | 2011-02-16 | 2015-08-19 | 诺瓦提斯公司 | 用于治疗神经变性疾病的治疗剂的组合物 |
| TWI592411B (zh) | 2011-02-23 | 2017-07-21 | 英特爾立秦有限責任公司 | 激酶抑制劑之組合及其用途 |
| US9127074B2 (en) * | 2011-03-07 | 2015-09-08 | Fondazione Telethon | TFEB variants and uses thereof |
| PH12013502077A1 (en) * | 2011-04-25 | 2013-12-16 | Novartis Ag | Combination of a phosphatidylinositol-3-kinase (pi3k) inhibitor and a mtor inhibitor |
| US20140357651A1 (en) * | 2011-05-04 | 2014-12-04 | Yi Liu | Combination pharmaceutical compositions and uses thereof |
| KR20140069235A (ko) | 2011-09-27 | 2014-06-09 | 노파르티스 아게 | 돌연변이체 idh의 억제제로서의 3-피리미딘-4-일-옥사졸리딘-2-온 |
| EP2776441A4 (en) * | 2011-11-08 | 2015-04-08 | Intellikine Llc | TREATMENT METHOD WITH MULTIPLE PHARMACEUTICAL AGENTS |
| US20130209543A1 (en) * | 2011-11-23 | 2013-08-15 | Intellikine Llc | Enhanced treatment regimens using mtor inhibitors |
| 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 |
| DK2968281T3 (da) | 2013-03-13 | 2020-11-02 | Univ Texas | Mtor-hæmmere til forebyggelse af vækst af tarmpolyp |
| SG11201507093WA (en) | 2013-03-14 | 2015-10-29 | Univ Maryland Baltimore Office Of Technology Transfer | Androgen receptor down-regulating agents and uses thereof |
| KR20150131224A (ko) | 2013-03-14 | 2015-11-24 | 노파르티스 아게 | 돌연변이 idh의 억제제로서의 3-피리미딘-4-일-옥사졸리딘-2-온 |
| KR20150130451A (ko) | 2013-03-15 | 2015-11-23 | 제넨테크, 인크. | 암 치료 방법 및 항암제 내성 예방을 위한 방법 |
| EA038235B1 (ru) * | 2013-05-01 | 2021-07-28 | Ф.Хоффманн-Ля Рош Аг | Бигетероарильные соединения и их применения |
| SG11201600525XA (en) | 2013-08-12 | 2016-02-26 | Tokai Pharmaceuticals Inc | Biomarkers for treatment of neoplastic disorders using androgen-targeted therapies |
| 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 |
| CA2933908C (en) | 2013-12-31 | 2024-01-30 | Rapamycin Holdings, Llc | Oral rapamycin nanoparticle preparations and use |
| US9700544B2 (en) | 2013-12-31 | 2017-07-11 | Neal K Vail | Oral rapamycin nanoparticle preparations |
| CA3019311A1 (en) | 2015-04-15 | 2016-10-20 | University Of Massachusetts | Compositions and methods for xi chromosome reactivation |
| EP3297629A1 (en) | 2015-05-20 | 2018-03-28 | Novartis AG | Pharmaceutical combination of everolimus with dactolisib |
| AU2017363970A1 (en) | 2016-11-23 | 2019-06-20 | Novartis Ag | Methods of enhancing immune response with everolimus, dactolisib or both |
| WO2019157516A1 (en) | 2018-02-12 | 2019-08-15 | 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 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SK18362002A3 (sk) * | 2000-06-26 | 2004-02-03 | Stressgen Biotechnologies Corporation | Použitie prostriedku s obsahom fúzneho proteínu |
| AR051388A1 (es) * | 2004-10-13 | 2007-01-10 | Wyeth Corp | Analogos de 17-hidroxiwortmanina como inhibidores de pi3k |
| KR20130087058A (ko) * | 2005-07-20 | 2013-08-05 | 노파르티스 아게 | 피리미딜아미노벤즈아미드와 mtor 키나제 억제제의 조합물 |
| EP1954699B1 (en) * | 2005-11-22 | 2012-09-19 | Kudos Pharmaceuticals Ltd | PYRIDO-, PYRAZO- AND PYRIMIDOPYRIMIDINE DERIVATIVES AS mTOR INHIBITORS |
| JO2660B1 (en) * | 2006-01-20 | 2012-06-17 | نوفارتيس ايه جي | Pi-3 inhibitors and methods of use |
| US7659274B2 (en) * | 2006-01-25 | 2010-02-09 | Osi Pharmaceuticals, Inc. | Unsaturated mTOR inhibitors |
| EP2012794B1 (en) * | 2006-04-13 | 2014-09-17 | The Trustees of Columbia University in the City of New York | Compositions and intraluminal devices for inhibiting vascular stenosis |
| EP2118087B1 (en) * | 2007-02-06 | 2012-03-28 | Novartis AG | Pi 3-kinase inhibitors and methods of their use |
| KR101472607B1 (ko) * | 2007-02-20 | 2014-12-15 | 노파르티스 아게 | 지질 키나제 및 mTOR의 이중 억제제로서의 이미다조퀴놀린 |
| US20100272717A1 (en) * | 2007-12-13 | 2010-10-28 | Novartis Ag | Combinations of therapeutic agents for treating cancer |
-
2009
- 2009-10-29 ES ES09744391.5T patent/ES2627677T3/es active Active
- 2009-10-29 AU AU2009309616A patent/AU2009309616B2/en not_active Ceased
- 2009-10-29 US US13/123,956 patent/US20110195966A1/en not_active Abandoned
- 2009-10-29 CA CA2736361A patent/CA2736361C/en not_active Expired - Fee Related
- 2009-10-29 WO PCT/EP2009/064274 patent/WO2010049481A1/en not_active Ceased
- 2009-10-29 EP EP09744391.5A patent/EP2349275B1/en not_active Not-in-force
- 2009-10-29 BR BRPI0921802A patent/BRPI0921802A8/pt not_active IP Right Cessation
- 2009-10-29 CN CN201510402018.9A patent/CN105030784A/zh active Pending
- 2009-10-29 CN CN2009801431736A patent/CN102202668A/zh active Pending
- 2009-10-29 RU RU2011121508/15A patent/RU2538683C2/ru not_active IP Right Cessation
- 2009-10-29 KR KR1020117009771A patent/KR20110090911A/ko not_active Ceased
- 2009-10-29 JP JP2011533721A patent/JP2012506898A/ja not_active Withdrawn
- 2009-10-29 MX MX2011004585A patent/MX2011004585A/es active IP Right Grant
-
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
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Also Published As
| Publication number | Publication date |
|---|---|
| MX2011004585A (es) | 2011-06-01 |
| AU2009309616B2 (en) | 2014-02-13 |
| CA2736361A1 (en) | 2010-05-06 |
| US20110195966A1 (en) | 2011-08-11 |
| AU2009309616A2 (en) | 2011-07-07 |
| RU2538683C2 (ru) | 2015-01-10 |
| BRPI0921802A2 (pt) | 2016-09-27 |
| JP2012506898A (ja) | 2012-03-22 |
| KR20110090911A (ko) | 2011-08-10 |
| JP2018197243A (ja) | 2018-12-13 |
| US20160136175A1 (en) | 2016-05-19 |
| EP2349275B1 (en) | 2017-03-08 |
| JP2015013883A (ja) | 2015-01-22 |
| EP2349275A1 (en) | 2011-08-03 |
| WO2010049481A1 (en) | 2010-05-06 |
| CN102202668A (zh) | 2011-09-28 |
| AU2009309616A1 (en) | 2010-05-06 |
| ES2627677T3 (es) | 2017-07-31 |
| RU2014115188A (ru) | 2015-10-20 |
| US20180133226A1 (en) | 2018-05-17 |
| BRPI0921802A8 (pt) | 2018-03-13 |
| JP2017002058A (ja) | 2017-01-05 |
| CA2736361C (en) | 2017-10-10 |
| RU2011121508A (ru) | 2012-12-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105030784A (zh) | 磷脂酰肌醇-3-激酶(PI3K)抑制剂和mTOR抑制剂的组合产品 | |
| CN108366992A (zh) | 蛋白水解靶向嵌合体化合物及其制备和应用方法 | |
| TWI602567B (zh) | 磷脂醯肌醇-3-激酶(pi3k)抑制劑及mtor抑制劑之組合 | |
| CN107427522B (zh) | 用于治疗黑素瘤的阿吡莫德 | |
| PT1615640E (pt) | Combinações antineoplásticas | |
| JP2013538876A (ja) | 併用医薬 | |
| MX2012012058A (es) | Combinacion de compuestos organicos. | |
| 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 | |
| HK1060062B (en) | Antineoplastic combinations comprising cci-779 (rapamycin derivative) together with gemcitabine or fluorouracil |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20151111 |
|
| WD01 | Invention patent application deemed withdrawn after publication |