Discovery and optimization of novel piperazines as potent inhibitors of fatty acid synthase (FASN) |
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| Authors: | Matthew W Martin David R Lancia Hongbin Li Shawn ER Schiller Angela V Toms Zhongguo Wang Kenneth W Bair Jennifer Castro Shawn Fessler Deepali Gotur Stephen E Hubbs Goss S Kauffman Mark Kershaw George P Luke Crystal McKinnon Lili Yao Wei Lu David S Millan |
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| Institution: | 1. FORMA Therapeutics, 500 Arsenal Street, Suite 100, Watertown, MA 02472, USA;2. FORMA Therapeutics, 35 Northeast Industrial Road, Branford, CT 06405, USA |
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| Abstract: | 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. |
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| Keywords: | Fatty acid synthase FASN Oncology Piperazines |
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