(R)-VX-11e是一种口服有效的选择性ERK抑制剂,对ERK1/2的IC50分别为17 nM和15 nM,选择性超其他激酶200倍以上;其(R)-对映体(R)-VX-11e同样为ERK2抑制剂。
[1] Aronov AM, Tang Q, Martinez-Botella G, Bemis GW, Cao J, Chen G, Ewing NP, Ford PJ, Germann UA, Green J, Hale MR, Jacobs M, Janetka JW, Maltais F, Markland W, Namchuk MN, Nanthakumar S, Poondru S, Straub J, ter Haar E, Xie X. Structure-guided design of potent and selective pyrimidylpyrrole inhibitors of extracellular signal-regulated kinase (ERK) using conformational control. J Med Chem. 2009 Oct 22;52(20):6362-8. doi: 10.1021/jm900630q. PMID: 19827834.[2]Krepler C, Xiao M, Sproesser K, Brafford PA, Shannan B, Beqiri M, Liu Q, Xu W, Garman B, Nathanson KL, Xu X, Karakousis GC, Mills GB, Lu Y, Ahmed TA, Poulikakos PI, Caponigro G, Boehm M, Peters M, Schuchter LM, Weeraratna AT, Herlyn M. Personalized Preclinical Trials in BRAF Inhibitor-Resistant Patient-Derived Xenograft Models Identify Second-Line Combination Therapies. Clin Cancer Res. 2016 Apr 1;22(7):1592-602. doi: 10.1158/1078-0432.CCR-15-1762. Epub 2015 Dec 16. PMID: 26673799; PMCID: PMC4818716.





