National Center for
5AK0: Human Pfkfb3 In Complex With An Indole Inhibitor 6
J. Med. Chem. (2015) 58 p.3611-3625
A weak screening hit with suboptimal physicochemical properties was optimized against PFKFB3 kinase using critical structure-guided insights. The resulting compounds demonstrated high selectivity over related PFKFB isoforms and modulation of the target in a cellular context. A selected example demonstrated exposure in animals following oral dosing. Examples from this series may serve as useful probes to understand the emerging biology of this metabolic target.