CDC42 binding protein kinase gamma (CDC42BPG) (CDC42BPG)

CDC42 binding protein kinase gamma (CDC42BPG), commonly known as DMPK2 or MRCK gamma, is a serine/threonine protein kinase that functions as a downstream effector of the small GTPase CDC42. It belongs to the AGC kinase family and is a member of the myotonic dystrophy protein kinase (DMPK) subfamily, sharing significant structural homology with MRCK alpha and beta. Unlike its ubiquitously expressed relatives, CDC42BPG is predominantly expressed in heart and skeletal muscle, where it is thought to play specialized roles in maintaining tissue structure and contractility. In the context of oncology, CDC42BPG is recognized for its role in promoting cancer cell migration and invasion by regulating actomyosin dynamics through the phosphorylation of myosin light chains. While no drugs targeting this kinase are currently FDA-approved, small-molecule inhibitors such as BDP9066 have shown preclinical promise in inhibiting the motility and proliferation of various cancer types, particularly hematological and skin cancers. A notable therapeutic challenge is the potential for systemic toxicity, given the protein's high expression in vital muscle and cardiac tissues, as well as the difficulty in achieving high selectivity over closely related kinases like ROCK.

Other names

DMPK2MRCK gammaMRCKGMyotonic dystrophy kinase-related CDC42-binding kinase gammaHSMDPKINKAPPA-200

Kinase inhibition (ATP-competitive inhibition of the catalytic domain)