MEK1 inhibitor, potent and ATP-uncompetitive
CAS：1168091-68-6
分子式：C16H14FIN4O3
分子量：456.21
纯度：98%
存储：Store at -20°C

Background:

GDC-0623 is a potent and ATP-uncompetitive inhibitor of MEK1 with Ki value of 0.13nM [1].

GDC-0623 is an allosteric MEK inhibitor and has efficacy against both mutant BRAF and mutant KRAS. In the cell viability assays, GDC-0623 inhibits BRAF (V600E) and KRAS (G13D) with EC50 values of 7nM and 42nM, respectively in A375 cells and HCT116 cells. Besides that, GDC-0623 shows similar efficacy in the two genotypes in a panel of BRAF and KRAS-mutant cancer cell lines. GDC-0623 is found to prevent MEK phosphorylation in cells, resulting in more effective inhibition of pERK. Furthermore, it is found that GDC-0623 blocks RAF activation through the effect on MEK. It induces dimerization of MEK with both BRAF and CRAF and stabilizes the RAF–MEK complex. In addition, GDC-0623 also suppresses RAF activation via inhibiting the formation of BRAF–CRAF heterodimer and the translocation of RAF in plasma membrane [1].

参考文献:
[1] Hatzivassiliou G, Haling J R, Chen H, et al. Mechanism of MEK inhibition determines efficacy in mutant KRAS-versus BRAF-driven cancers. Nature, 2013, 501(7466): 232-236.