Identification of TRD‐35 as Potent and Selective DRAK2 Inhibitor.

DAP kinase-related apoptosis-inducing protein kinase 2 (DRAK2) is a member of the death-associated protein kinase (DAPK) family[1] and originally identified as a proapoptotic protein with the ability to induce apoptosis when overexpressed in various cell types.[2] However, the apoptosis-inducing ability of DRAK2 seems to be controversial and influenced by cellular factors within a specific cell types.[[3]] Recently, it has been suggested that DRAK2 is closely involved in tumorigenesis; DRAK2 expression was found to be highly elevated in multiple tumor types such as basal-like and HER2-enriched breast cancers. B Vertex-3 b is a pyrimidine C5-methylated analog of B UC-3 b .[9] When B UC-3 b was assessed to ATP-binding site of 359 diverse kinases at 10 micromolar concentration, it bound to 337 kinases including CDK2, CDK5, JNK3, and others. We believe the nitrile of the B UC-3 b has hydrogen-bonding interaction to DRAK2 Lys62 and plays a key role for its kinase promiscuous activities. [Extracted from the article]