917879-39-1
917879-39-1 結(jié)構(gòu)式
基本信息
Mk-2461 .
Mk-2461 USP/EP/BP
MK-2461
MK2461
MK 2461
9-[[[(2R)-1,4-DIOXAN-2-YL]METHYL-METHYLSULFAMOYL]AMINO]-2-(1-METHYLPYRAZOL-4-YL)-11-OXOBENZO[1,2]CYCLOHEPTA[2,4-B]PYRIDINE
N-((2R)-1,4-Dioxan-2-ylmethyl)-N-methyl-N'-[3-(1-methyl-1H-pyrazol-4-yl)-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl]sulfamide
Sulfamide, N-[(2R)-1,4-dioxan-2-ylmethyl]-N-methyl-N'-[3-(1-methyl-1H-pyrazol-4-yl)-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl]-
N-[(2R)-1,4-dioxan-2-ylMethyl]-N-Methyl{[5-(1-Methyl-1H-pyrazol-4-yl)-2-oxo-7-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,9,12,14-heptaen-14-yl]aMino}sulfonaMide
Mk-2461 . N-[(2R)-1,4-dioxan-2-ylMethyl]-N-Methyl{[5-(1-Methyl-1H-pyrazol-4-yl)-2-oxo-7-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,9,12,14-heptaen-14-yl]aMino}sulfonaMide
物理化學(xué)性質(zhì)
常見問題列表
| Target | Value |
| c-Met (M1250T) | 0.4 nM |
| c-Met (Y1235D) | 0.5 nM |
| c-Met (Y1230H) | 1.0 nM |
| c-Met (N1100) | 1.5 nM |
| c-Met (Y1230C) | 1.5 nM |
MK-2461能有效抑制FGFR1, FGFR2, FGFR3, KDR, TrkA, TrkB和Flt4，IC50分別為65 nM, 39 nM, 50 nM, 44 nM, 46 nM, 61 nM,和 78 nM。相比于野生型c-Met,，MK-2461更有效地抑制致原癌基因c-Met突變體 N1100Y, Y1230C, Y1230H, Y1235D,和M1250Tn1100y， IC 50分別為1.5 nM, 1.5 nM, 1.0 nM, 0.5 nM, 和0.4 nM。MK-2461與磷酸化c - met結(jié)合更強(qiáng)。MK-2461有效抑制ATP誘導(dǎo)的c-Met自身磷酸化產(chǎn)生在羧基端對(duì)接域，而不是激活環(huán)。與此相反，MK-2461在Kato III細(xì)胞和h1703細(xì)胞中抑制FGFR2 (Y653/Y654)和 PDGFR-α (Y849)的激活環(huán)磷酸活化，IC 50均 < 0.3μM。MK-2461在4MBr-5細(xì)胞中抑制肝細(xì)胞生長(zhǎng)因子誘導(dǎo)的絲裂原，IC 50為204nM，和在HPAF II 細(xì)胞中肝細(xì)胞生長(zhǎng)因子誘導(dǎo)的遷移，IC 50為404 nM，以及肝細(xì)胞生長(zhǎng)因子誘導(dǎo)的MDCK細(xì)胞分支管型的形成。此外，MK-2461有效抑制由還Tpr-Met或Tpr-Met（y362c）突變的32D細(xì)胞中IL-3非依賴性增殖，IC 50 為~ 100nM。MK-2461明顯抑制廣譜腫瘤細(xì)胞系增殖，特別是針對(duì)高表達(dá)MET和FGFR2的癌細(xì)胞。