Discovery and Characterization of ZL-2201, a Potent, Highly Selective, and Orally Bioavailable Small-molecule DNA-PK Inhibitor

DNA-dependent protein kinase (DNA-PK) plays an important role in the overall survival and proliferation of cells, making this enzyme an intriguing target for the treatment of a variety of cancers.  In our latest publication, WuXi AppTec scientists contributed to the discovery and characterization of ZL-2201, a potent and highly selective small molecule DNA-PK inhibitor.  In vivo oral administration of ZL-2201 demonstrated dose-dependent antitumor activity in a xenograft model and significantly enhanced the activity of approved DNA damaging agents.