MK-2461

一种c-MET抑制剂（对野生型和突变型c-MET的IC50值为0.4-2nM）；在包含13种其他激酶的测试中，该抑制剂对c-MET具有选择性（IC50值为22-7800nM），但也会抑制Ron和FLT1（IC50值分别为7nM和10nM）。在KATO III细胞中，该抑制剂以2µM浓度抑制FGFR2和PDGFRα的自磷酸化；在一系列癌细胞系中，包括表达持续激活的c-MET、FGFR2或PDGFR的细胞系中，该抑制剂可减少细胞增殖（所有细胞系的IC50值均≤1µM）；在GTL-16胃癌小鼠异种移植模型中，该抑制剂可减少肿瘤生长（剂量范围为10-200mg/kg）。A c-MET inhibitor (IC50s = 0.4-2 nM for wild-type and mutant forms); selective for c-MET over a panel of 13 additional kinases (IC50s = 22-7,800 nM) but does inhibit Ron and FLT1 (IC50s = 7 and 10 nM, respectively); inhibits autophosphorylation of FGFR2 and PDGFRα in KATO III cells at 2 µM; reduces proliferation in a panel of cancer cell lines, including cells expressing constitutively active c-MET, FGFR2, or PDGFR (IC50s = ≤ 1 µM for all); reduces tumor growth in a GTL-16 gastric cancer mouse xenograft model (10-200 mg/kg).分子式C24H25N5O5S分子量495.6O=C1C2=CC(C3=CN(N=C3)C)=CN=C2C=CC4=CC=C(NS(N(C)C[C@@H]5COCCO5)(=O)=O)C=C41