Developing Therapeutic Candidates for Rare ADCK3-amplified Cancers

National Center For Advancing Translational Sciences

Investigators

Linked publications, trials & patents

Abstract

Starting with a known p38 inhibitor, R1487, which has a Kd value of 320 nM against ADCK3, the project team identified a series of potent and selective ADCK3 inhibitors. Comprehensive kinome profiling studies of compounds TRND00843898 and TRND00858176 demonstrated that they are highly selective ADCK3 inhibitors, exhibiting single-digit nM Kd values. In particular, TRND00858176 has good solubility and pharmacokinetic (PK) properties, and could serve as a biological probe for further studying ADCK3-related biology. It is currently being screened in the NCI-60 cell line panel to identify additional cancers in which it could be further evaluated.