Background:

TAK-733 is a potent, ATP-noncompetitive and selective inhibitor of MEK allosteric site with the IC50 value of 3.2nM [1].

TAK-733 has been shown potent enzymatic and cell activity with an IC50 value of 3.2nM against constitutively active MEK enzyme and an EC50 of 1.9nM against ERK phosphorylation in cells. In addition, TAK-733 has also shown the low clearance and high oral bioavailability based on the pharmacokinetics of TAK-733 in all species (Mouse, rat, dog and Monkey). Furthermore, TAK-733 has been reported to broad inhibit tumor activity in mouse xenograft models of human cancer (melanoma, colorectal, NSCLC, pancreatic and breast cancer) [1].

参考文献:
[1] Dong Q1, Dougan DR, Gong X, Halkowycz P, Jin B, Kanouni T, O'Connell SM, Scorah N, Shi L, Wallace MB, Zhou F. Discovery of TAK-733, a potent and selective MEK allosteric site inhibitor for the treatment of cancer. Bioorg Med Chem Lett. 2011 Mar 1;21(5):1315-9. doi: 10.1016/j.bmcl.2011.01.071. Epub 2011 Jan 22.