SGC-GAK-1 (2226517-76-4) is a highly potent and selective inhibitor of cyclin G associated kinase (GAK), a member of the numb-associated kinase (NAK) family involved in membrane trafficking and sorting of proteins and is required for the maintenance of centrosome maturation and progression though mitosis. KD = 1.9 nM with >50-fold selectivity against a panel of 400 kinases. It also displayed affinity for RIPK2 (KD = 110 nM) and ADCK3 (KD = 190 nM). SGC-GAK-1 displayed potent cellular activity in HEK293T cells (IC50 = 120 nM) and showed strong growth inhibition in the prostate cancer cell lines LNCaP (IC50 = 0.65 µM) and 22Rv1 (IC50 = 0.17 µM).
1) Asquith et al. (2019), SGC-GAK-1: A Chemical Probe for Cyclin G Associated Kinase (GAK); J. Med. Chem., 62 2830