4区 · 医学
Article
作者: Martin, Matthew W. ; Lancia, David R. Jr. ; Li, Hongbin ; Schiller, Shawn E. R. ; Toms, Angela V. ; Wang, Zhongguo ; Bair, Kenneth W. ; Castro, Jennifer ; Fessler, Shawn ; Gotur, Deepali ; Hubbs, Stephen E. ; Kauffman, Goss S. ; Kershaw, Mark ; Luke, George P. ; McKinnon, Crystal ; Yao, Lili ; Lu, Wei ; Millan, David S.
The discovery, structure-activity relationships, and optimization of a novel class of fatty acid synthase (FASN) inhibitors is reported. High throughput screening identified a series of substituted piperazines with structural features that enable interactions with many of the potency-driving regions of the FASN KR domain binding site. Derived from this series was FT113, a compound with potent biochemical and cellular activity, which translated into excellent activity in in vivo models.