TW201332550A - 治療胃腸道基質瘤之方法 - Google Patents
治療胃腸道基質瘤之方法 Download PDFInfo
- Publication number
- TW201332550A TW201332550A TW101139801A TW101139801A TW201332550A TW 201332550 A TW201332550 A TW 201332550A TW 101139801 A TW101139801 A TW 101139801A TW 101139801 A TW101139801 A TW 101139801A TW 201332550 A TW201332550 A TW 201332550A
- Authority
- TW
- Taiwan
- Prior art keywords
- gist
- imatinib
- inhibitor
- kit
- pharmaceutically acceptable
- Prior art date
Links
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 title claims abstract description 109
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 title abstract description 90
- 238000000034 method Methods 0.000 title abstract description 15
- 239000005517 L01XE01 - Imatinib Substances 0.000 claims abstract description 76
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 claims abstract description 76
- 229960002411 imatinib Drugs 0.000 claims abstract description 73
- 238000011282 treatment Methods 0.000 claims abstract description 23
- 239000002147 L01XE04 - Sunitinib Substances 0.000 claims abstract description 22
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 22
- 229940124204 C-kit inhibitor Drugs 0.000 claims abstract description 20
- 239000012828 PI3K inhibitor Substances 0.000 claims abstract description 20
- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 claims abstract description 20
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 claims abstract description 20
- 229960001796 sunitinib Drugs 0.000 claims abstract description 20
- 229940125829 fibroblast growth factor receptor inhibitor Drugs 0.000 claims abstract description 17
- 150000003839 salts Chemical class 0.000 claims description 43
- HHZIURLSWUIHRB-UHFFFAOYSA-N nilotinib Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HHZIURLSWUIHRB-UHFFFAOYSA-N 0.000 claims description 18
- 239000005536 L01XE08 - Nilotinib Substances 0.000 claims description 17
- 229960001346 nilotinib Drugs 0.000 claims description 16
- XZRJIQYSYAYMBR-VWMHFEHESA-N CC(CCCCCCCC)N.N1([C@@H](CCC1)C(=O)O)C(=O)O Chemical compound CC(CCCCCCCC)N.N1([C@@H](CCC1)C(=O)O)C(=O)O XZRJIQYSYAYMBR-VWMHFEHESA-N 0.000 claims description 5
- JOGKUKXHTYWRGZ-UHFFFAOYSA-N dactolisib Chemical group O=C1N(C)C2=CN=C3C=CC(C=4C=C5C=CC=CC5=NC=4)=CC3=C2N1C1=CC=C(C(C)(C)C#N)C=C1 JOGKUKXHTYWRGZ-UHFFFAOYSA-N 0.000 claims description 4
- 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 description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000002139 L01XE22 - Masitinib Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 229960004655 masitinib Drugs 0.000 claims description 2
- WJEOLQLKVOPQFV-UHFFFAOYSA-N masitinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3SC=C(N=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 WJEOLQLKVOPQFV-UHFFFAOYSA-N 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 41
- 150000001875 compounds Chemical class 0.000 description 27
- 239000003112 inhibitor Substances 0.000 description 23
- 108091008794 FGF receptors Proteins 0.000 description 17
- QADPYRIHXKWUSV-UHFFFAOYSA-N BGJ-398 Chemical compound C1CN(CC)CCN1C(C=C1)=CC=C1NC1=CC(N(C)C(=O)NC=2C(=C(OC)C=C(OC)C=2Cl)Cl)=NC=N1 QADPYRIHXKWUSV-UHFFFAOYSA-N 0.000 description 16
- 206010028980 Neoplasm Diseases 0.000 description 15
- 102000052178 fibroblast growth factor receptor activity proteins Human genes 0.000 description 15
- 125000000217 alkyl group Chemical group 0.000 description 13
- 239000003795 chemical substances by application Substances 0.000 description 11
- 230000035772 mutation Effects 0.000 description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 10
- 229910052739 hydrogen Inorganic materials 0.000 description 10
- 239000001257 hydrogen Substances 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 229910052736 halogen Inorganic materials 0.000 description 9
- 150000002367 halogens Chemical class 0.000 description 9
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 9
- 229940126062 Compound A Drugs 0.000 description 7
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 230000001394 metastastic effect Effects 0.000 description 7
- 206010061289 metastatic neoplasm Diseases 0.000 description 7
- 230000004083 survival effect Effects 0.000 description 7
- 102100038332 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Human genes 0.000 description 6
- 230000009036 growth inhibition Effects 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 description 5
- 239000005511 L01XE05 - Sorafenib Substances 0.000 description 5
- 108010029485 Protein Isoforms Proteins 0.000 description 5
- 102000001708 Protein Isoforms Human genes 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 5
- 125000004093 cyano group Chemical group *C#N 0.000 description 5
- -1 cyano, imidazolyl Chemical group 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- 230000037361 pathway Effects 0.000 description 5
- 238000002271 resection Methods 0.000 description 5
- 229960003787 sorafenib Drugs 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 4
- 239000002138 L01XE21 - Regorafenib Substances 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 230000003321 amplification Effects 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000002301 combined effect Effects 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 238000009093 first-line therapy Methods 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 125000001072 heteroaryl group Chemical group 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- 150000002632 lipids Chemical class 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 238000003199 nucleic acid amplification method Methods 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- FNHKPVJBJVTLMP-UHFFFAOYSA-N regorafenib Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=C(F)C(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 FNHKPVJBJVTLMP-UHFFFAOYSA-N 0.000 description 4
- 229960004836 regorafenib Drugs 0.000 description 4
- 230000004654 survival pathway Effects 0.000 description 4
- 230000002195 synergetic effect Effects 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- RHKWIGHJGOEUSM-UHFFFAOYSA-N 3h-imidazo[4,5-h]quinoline Chemical class C1=CN=C2C(N=CN3)=C3C=CC2=C1 RHKWIGHJGOEUSM-UHFFFAOYSA-N 0.000 description 3
- 101000605639 Homo sapiens Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Proteins 0.000 description 3
- 101710093328 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Proteins 0.000 description 3
- 108091000080 Phosphotransferase Proteins 0.000 description 3
- 230000001028 anti-proliverative effect Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 3
- 229960000367 inositol Drugs 0.000 description 3
- 125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 description 3
- 102000020233 phosphotransferase Human genes 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 3
- 150000003230 pyrimidines Chemical class 0.000 description 3
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 3
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 238000011269 treatment regimen Methods 0.000 description 3
- NHFDRBXTEDBWCZ-ZROIWOOFSA-N 3-[2,4-dimethyl-5-[(z)-(2-oxo-1h-indol-3-ylidene)methyl]-1h-pyrrol-3-yl]propanoic acid Chemical compound OC(=O)CCC1=C(C)NC(\C=C/2C3=CC=CC=C3NC\2=O)=C1C NHFDRBXTEDBWCZ-ZROIWOOFSA-N 0.000 description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- 206010061818 Disease progression Diseases 0.000 description 2
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 2
- 102100021066 Fibroblast growth factor receptor substrate 2 Human genes 0.000 description 2
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
- 101000818410 Homo sapiens Fibroblast growth factor receptor substrate 2 Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 2
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 2
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 2
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 238000009098 adjuvant therapy Methods 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 230000005754 cellular signaling Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 230000005750 disease progression Effects 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 229960002989 glutamic acid Drugs 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- 230000002055 immunohistochemical effect Effects 0.000 description 2
- 210000004495 interstitial cells of cajal Anatomy 0.000 description 2
- WOSKHXYHFSIKNG-UHFFFAOYSA-N lenvatinib Chemical compound C=12C=C(C(N)=O)C(OC)=CC2=NC=CC=1OC(C=C1Cl)=CC=C1NC(=O)NC1CC1 WOSKHXYHFSIKNG-UHFFFAOYSA-N 0.000 description 2
- 229960003784 lenvatinib Drugs 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 201000008806 mesenchymal cell neoplasm Diseases 0.000 description 2
- LBWFXVZLPYTWQI-IPOVEDGCSA-N n-[2-(diethylamino)ethyl]-5-[(z)-(5-fluoro-2-oxo-1h-indol-3-ylidene)methyl]-2,4-dimethyl-1h-pyrrole-3-carboxamide;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C LBWFXVZLPYTWQI-IPOVEDGCSA-N 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 230000002980 postoperative effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000004393 prognosis Methods 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 238000013517 stratification Methods 0.000 description 2
- 229940034785 sutent Drugs 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 125000001425 triazolyl group Chemical group 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- VRQMAABPASPXMW-HDICACEKSA-N AZD4547 Chemical compound COC1=CC(OC)=CC(CCC=2NN=C(NC(=O)C=3C=CC(=CC=3)N3C[C@@H](C)N[C@@H](C)C3)C=2)=C1 VRQMAABPASPXMW-HDICACEKSA-N 0.000 description 1
- 206010069754 Acquired gene mutation Diseases 0.000 description 1
- BMMXYEBLEBULND-UHFFFAOYSA-N BGT226 free base Chemical compound C1=NC(OC)=CC=C1C1=CC=C(N=CC2=C3N(C=4C=C(C(N5CCNCC5)=CC=4)C(F)(F)F)C(=O)N2C)C3=C1 BMMXYEBLEBULND-UHFFFAOYSA-N 0.000 description 1
- 238000003734 CellTiter-Glo Luminescent Cell Viability Assay Methods 0.000 description 1
- 206010061819 Disease recurrence Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 102100039563 ETS translocation variant 1 Human genes 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- 101000813729 Homo sapiens ETS translocation variant 1 Proteins 0.000 description 1
- 208000005016 Intestinal Neoplasms Diseases 0.000 description 1
- 239000002137 L01XE24 - Ponatinib Substances 0.000 description 1
- 208000007433 Lymphatic Metastasis Diseases 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 101150033052 MAS5 gene Proteins 0.000 description 1
- 206010027457 Metastases to liver Diseases 0.000 description 1
- 206010051676 Metastases to peritoneum Diseases 0.000 description 1
- 206010027480 Metastatic malignant melanoma Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 101001059385 Mus musculus Formin-like protein 2 Proteins 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 description 1
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 1
- 241000282320 Panthera leo Species 0.000 description 1
- 102000001892 Protein Kinase C-theta Human genes 0.000 description 1
- 108010015499 Protein Kinase C-theta Proteins 0.000 description 1
- 239000012083 RIPA buffer Substances 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 1
- 101100344462 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) YDJ1 gene Proteins 0.000 description 1
- 206010066901 Treatment failure Diseases 0.000 description 1
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000013553 cell monolayer Substances 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000003570 cell viability assay Methods 0.000 description 1
- 238000012054 celltiter-glo Methods 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000011340 continuous therapy Methods 0.000 description 1
- 238000011393 cytotoxic chemotherapy Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 229940080856 gleevec Drugs 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000003331 infrared imaging Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 201000009019 intestinal benign neoplasm Diseases 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 201000010904 malignant hemangioma Diseases 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 210000000713 mesentery Anatomy 0.000 description 1
- 208000021039 metastatic melanoma Diseases 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- RAHBGWKEPAQNFF-UHFFFAOYSA-N motesanib Chemical compound C=1C=C2C(C)(C)CNC2=CC=1NC(=O)C1=CC=CN=C1NCC1=CC=NC=C1 RAHBGWKEPAQNFF-UHFFFAOYSA-N 0.000 description 1
- 229950003968 motesanib Drugs 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229960004378 nintedanib Drugs 0.000 description 1
- XZXHXSATPCNXJR-ZIADKAODSA-N nintedanib Chemical compound O=C1NC2=CC(C(=O)OC)=CC=C2\C1=C(C=1C=CC=CC=1)\NC(C=C1)=CC=C1N(C)C(=O)CN1CCN(C)CC1 XZXHXSATPCNXJR-ZIADKAODSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 210000002747 omentum Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 229960001131 ponatinib Drugs 0.000 description 1
- PHXJVRSECIGDHY-UHFFFAOYSA-N ponatinib Chemical compound C1CN(C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)C1=CC=C(C)C(C#CC=2N3N=CC=CC3=NC=2)=C1 PHXJVRSECIGDHY-UHFFFAOYSA-N 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 239000003531 protein hydrolysate Substances 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 229960000329 ribavirin Drugs 0.000 description 1
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 108091006024 signal transducing proteins Proteins 0.000 description 1
- 102000034285 signal transducing proteins Human genes 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 230000037439 somatic mutation Effects 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 229940069905 tasigna Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 239000012224 working solution Substances 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161552633P | 2011-10-28 | 2011-10-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW201332550A true TW201332550A (zh) | 2013-08-16 |
Family
ID=47116505
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW101139801A TW201332550A (zh) | 2011-10-28 | 2012-10-26 | 治療胃腸道基質瘤之方法 |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US20140288073A1 (enExample) |
| EP (1) | EP2770999A1 (enExample) |
| JP (1) | JP2014532647A (enExample) |
| KR (1) | KR20140096035A (enExample) |
| CN (1) | CN103889422A (enExample) |
| AU (1) | AU2012328979B2 (enExample) |
| BR (1) | BR112014009993A2 (enExample) |
| CA (1) | CA2853095A1 (enExample) |
| CL (1) | CL2014001062A1 (enExample) |
| IL (1) | IL231943A0 (enExample) |
| MX (1) | MX2014005130A (enExample) |
| PH (1) | PH12014500897A1 (enExample) |
| RU (1) | RU2014120792A (enExample) |
| SG (1) | SG11201400543TA (enExample) |
| TN (1) | TN2014000093A1 (enExample) |
| TW (1) | TW201332550A (enExample) |
| WO (1) | WO2013063000A1 (enExample) |
| ZA (1) | ZA201401622B (enExample) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8754114B2 (en) | 2010-12-22 | 2014-06-17 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of FGFR3 |
| PE20190736A1 (es) | 2012-06-13 | 2019-05-23 | Incyte Holdings Corp | Compuestos triciclicos sustituidos como inhibidores del receptor del factor de crecimiento de fibroblastos (fgfr) |
| KR20150036014A (ko) * | 2012-07-11 | 2015-04-07 | 노파르티스 아게 | 위장 기질 종양을 치료하는 방법 |
| WO2014026125A1 (en) | 2012-08-10 | 2014-02-13 | Incyte Corporation | Pyrazine derivatives as fgfr inhibitors |
| US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
| KR102269032B1 (ko) | 2013-04-19 | 2021-06-24 | 인사이트 홀딩스 코포레이션 | Fgfr 저해제로서 이환식 헤테로사이클 |
| WO2014191938A1 (en) * | 2013-05-31 | 2014-12-04 | Novartis Ag | Combination therapy containing a pi3k-alpha inhibitor and fgfr kinase inhibitor for treating cancer |
| CA2927708C (en) | 2013-10-17 | 2021-05-25 | Sartar Therapeutics Ltd | Compositions comprising phosphodiesterase inhibitors for use in the treatment of a solid tumor in a human patient |
| US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| ES2895769T3 (es) | 2015-02-20 | 2022-02-22 | Incyte Corp | Heterociclos bicíclicos como inhibidores de FGFR |
| US9580423B2 (en) | 2015-02-20 | 2017-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
| WO2017086332A1 (ja) * | 2015-11-19 | 2017-05-26 | 国立大学法人金沢大学 | 間葉系ｋｒａｓ変異型がん治療剤 |
| AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
| SG11202010882XA (en) | 2018-05-04 | 2020-11-27 | Incyte Corp | Salts of an fgfr inhibitor |
| SI3788047T1 (sl) | 2018-05-04 | 2024-11-29 | Incyte Corporation | Trdne oblike inhibitorja fgfr in postopki priprave le-teh |
| TW202039862A (zh) * | 2018-11-12 | 2020-11-01 | 美商藍印藥品公司 | 受體酪氨酸激酶(kit)基因突變 |
| WO2020185532A1 (en) | 2019-03-08 | 2020-09-17 | Incyte Corporation | Methods of treating cancer with an fgfr inhibitor |
| US11591329B2 (en) | 2019-07-09 | 2023-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| WO2021067374A1 (en) | 2019-10-01 | 2021-04-08 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| US11607416B2 (en) | 2019-10-14 | 2023-03-21 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| US11566028B2 (en) | 2019-10-16 | 2023-01-31 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| WO2021113462A1 (en) | 2019-12-04 | 2021-06-10 | Incyte Corporation | Derivatives of an fgfr inhibitor |
| EP4069696A1 (en) | 2019-12-04 | 2022-10-12 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| WO2021146424A1 (en) | 2020-01-15 | 2021-07-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| CN112210541B (zh) * | 2020-10-14 | 2022-11-15 | 上海市普陀区利群医院 | 一种胃肠道间质瘤耐药细胞模型及其构建方法和应用 |
| WO2022221170A1 (en) | 2021-04-12 | 2022-10-20 | Incyte Corporation | Combination therapy comprising an fgfr inhibitor and a nectin-4 targeting agent |
| WO2022261160A1 (en) | 2021-06-09 | 2022-12-15 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| WO2022261159A1 (en) | 2021-06-09 | 2022-12-15 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5521184A (en) | 1992-04-03 | 1996-05-28 | Ciba-Geigy Corporation | Pyrimidine derivatives and processes for the preparation thereof |
| CO4940418A1 (es) | 1997-07-18 | 2000-07-24 | Novartis Ag | Modificacion de cristal de un derivado de n-fenil-2- pirimidinamina, procesos para su fabricacion y su uso |
| GB0202873D0 (en) | 2002-02-07 | 2002-03-27 | Novartis Ag | Organic compounds |
| GB0209265D0 (en) | 2002-04-23 | 2002-06-05 | Novartis Ag | Organic compounds |
| GB0215676D0 (en) | 2002-07-05 | 2002-08-14 | Novartis Ag | Organic compounds |
| GB0512324D0 (en) | 2005-06-16 | 2005-07-27 | Novartis Ag | Organic compounds |
| GB0510390D0 (en) * | 2005-05-20 | 2005-06-29 | Novartis Ag | Organic compounds |
| GT200600315A (es) | 2005-07-20 | 2007-03-19 | Formas cristalinas de 4-metilo-n-[3-(4-metilo-imidazol-1-ilo)-5-trifluorometilo-fenilo]-3-(4-pyridina-3-ilo-pirimidina-2-iloamino)-benzamida | |
| GT200600316A (es) | 2005-07-20 | 2007-04-02 | Sales de 4-metilo-n-(3-(4-metilo-imidazol-1-ilo)-5-trifluorometilo-fenilo)-3-(4-piridina-3-ilo-pirimidina-2-iloamino)- benzamida. | |
| JO2660B1 (en) * | 2006-01-20 | 2012-06-17 | نوفارتيس ايه جي | Pi-3 inhibitors and methods of use |
| EP1923053A1 (en) | 2006-09-27 | 2008-05-21 | Novartis AG | Pharmaceutical compositions comprising nilotinib or its salt |
| RS53020B (sr) * | 2007-04-11 | 2014-04-30 | Exelixis Inc. | Kombinovane terapije koje sadrže hinoksalin inhibitor pi3k-alfa za upotrebu u lečenju kancera |
| ES2554513T3 (es) | 2008-05-23 | 2015-12-21 | Novartis Ag | Derivados de quinolinas y quinoxalinas como inhibidores de la proteína tirosina quinasa |
| EP2297912A4 (en) * | 2008-07-01 | 2016-11-30 | Ikanos Communications Inc | VECTORED DSL WITH REDUCED MEMORY |
| UA104147C2 (uk) * | 2008-09-10 | 2014-01-10 | Новартис Аг | Похідна піролідиндикарбонової кислоти та її застосування у лікуванні проліферативних захворювань |
-
2012
- 2012-10-24 JP JP2014538891A patent/JP2014532647A/ja active Pending
- 2012-10-24 BR BR112014009993A patent/BR112014009993A2/pt not_active IP Right Cessation
- 2012-10-24 WO PCT/US2012/061532 patent/WO2013063000A1/en not_active Ceased
- 2012-10-24 US US14/353,186 patent/US20140288073A1/en not_active Abandoned
- 2012-10-24 RU RU2014120792/15A patent/RU2014120792A/ru not_active Application Discontinuation
- 2012-10-24 KR KR1020147010940A patent/KR20140096035A/ko not_active Withdrawn
- 2012-10-24 EP EP12780391.4A patent/EP2770999A1/en not_active Withdrawn
- 2012-10-24 CA CA2853095A patent/CA2853095A1/en not_active Abandoned
- 2012-10-24 PH PH1/2014/500897A patent/PH12014500897A1/en unknown
- 2012-10-24 CN CN201280052892.9A patent/CN103889422A/zh active Pending
- 2012-10-24 MX MX2014005130A patent/MX2014005130A/es not_active Application Discontinuation
- 2012-10-24 AU AU2012328979A patent/AU2012328979B2/en not_active Expired - Fee Related
- 2012-10-24 SG SG11201400543TA patent/SG11201400543TA/en unknown
- 2012-10-26 TW TW101139801A patent/TW201332550A/zh unknown
-
2014
- 2014-03-04 ZA ZA2014/01622A patent/ZA201401622B/en unknown
- 2014-03-06 TN TNP2014000093A patent/TN2014000093A1/en unknown
- 2014-04-03 IL IL231943A patent/IL231943A0/en unknown
- 2014-04-25 CL CL2014001062A patent/CL2014001062A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP2014532647A (ja) | 2014-12-08 |
| EP2770999A1 (en) | 2014-09-03 |
| BR112014009993A2 (pt) | 2017-04-25 |
| RU2014120792A (ru) | 2015-12-10 |
| CA2853095A1 (en) | 2013-05-02 |
| ZA201401622B (en) | 2015-12-23 |
| US20140288073A1 (en) | 2014-09-25 |
| PH12014500897A1 (en) | 2019-10-07 |
| CL2014001062A1 (es) | 2014-10-10 |
| MX2014005130A (es) | 2014-08-27 |
| AU2012328979A1 (en) | 2014-05-15 |
| TN2014000093A1 (en) | 2015-07-01 |
| IL231943A0 (en) | 2014-05-28 |
| NZ622155A (en) | 2015-12-24 |
| SG11201400543TA (en) | 2014-08-28 |
| WO2013063000A1 (en) | 2013-05-02 |
| KR20140096035A (ko) | 2014-08-04 |
| AU2012328979B2 (en) | 2016-04-21 |
| CN103889422A (zh) | 2014-06-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TW201332550A (zh) | 治療胃腸道基質瘤之方法 | |
| US20150202203A1 (en) | Method of Treating Gastrointestinal Stromal Tumors | |
| WO2013063003A1 (en) | Method of treating gastrointestinal stromal tumors | |
| RU2728579C2 (ru) | Хиральные диарильные макроциклы и их применение | |
| JP6970217B2 (ja) | ＰＩ３Ｋインヒビターとｃ−Ｍｅｔインヒビターの組み合わせ | |
| KR20160100975A (ko) | 제약 조합물 | |
| JP2016522247A (ja) | 組合せ医薬 | |
| JP2016529285A (ja) | 細胞増殖性疾患を治療するためのａｌｋ阻害剤とｃｄｋ阻害剤との組合せ | |
| KR20200036879A (ko) | 3세대 egfr 타이로신 키나아제 억제제 및 사이클린 d 키나아제 억제제의 치료적 조합물 | |
| US20160095842A1 (en) | Combination therapy containing a pi3k-alpha inhibitor and fgfr kinase inhibitor for treating cancer | |
| US20160228451A1 (en) | ROCK in Combination with MAPK Pathway | |
| ES2608585T3 (es) | Derivados de pirimidilaminobenzamida para su uso en el tratamiento de una enfermedad mieloproliferativa inducida por TEL-PDGFRbeta | |
| TW201332551A (zh) | 治療胃腸道基質瘤之方法 | |
| NZ622155B2 (en) | Method of treating gastrointestinal stromal tumors | |
| TWI554502B (zh) | 受體型激酶調節劑及治療多囊性腎疾病的方法 | |
| Shrestha | Combination of ALK and MEK inhibitors for the treatment of ALK-positive non-small cell lung cancer | |
| KR20250055574A (ko) | 병용 의약 | |
| McCubrey et al. | New agents and approaches for targeting the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR cell survival pathways |