Background:

BX795, a small molecule with an aminopyrimidine backbone in its chemical structure, is a potent and ATP-competitive inhibitor of 3-phosphoinositide-dependent kinase 1 (PDK1) that binds to the ATP binding pocket of PDK1 and hence potently inhibits the enzymatic activity of PDK1 in a direct kinase assay format with a value of 50% concentration inhibition IC₅₀of 11 nM. BX795 is also a potent and selectively inhibitor of TANK-binding kinase 1 (TBK1) and IκB kinase ε (IKKε), with values of IC₅₀of 0.006 μM and 0.041 μM respectively, that blocks the phosphorylation, nuclear translocation and transcriptional activity of interferon regulatory factor 3 as well as the production of interferon-β in macrophages stimulated with poly(I:C) or lipopolysaccharide (LPS).

Reference

Feldman RI, Wu JM, Polokoff MA, Kochanny MJ, Dinter H, Zhu D, Biroc SL, Alicke B, Bryant J, Yuan S, Buckman BO, Lentz D, Ferrer M, Whitlow M, Adler M, Finster S, Chang Z, Arnaiz DO. Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1. J Biol Chem. 2005 May 20;280(20):19867-74.

Clark K, Plater L, Peggie M, Cohen P. Use of the pharmacological inhibitor BX795 to study the regulation and physiological roles of TBK1 and IkappaB kinase epsilon: a distinct upstream kinase mediates Ser-172 phosphorylation and activation. J Biol Chem. 2009 May 22;284(21):14136-46.