6NNA

Human Fatty Acid Synthase Psi/KR Tri-Domain with NADPH and Compound 22

Summary for 6NNA

• Entry DOI: 10.2210/pdb6nna/pdb
• Descriptor: Fatty acid synthase,Fatty acid synthase, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, {4-[4-(1,3-benzoxazol-2-yl)benzene-1-carbonyl]piperazin-1-yl}(1-hydroxycyclopropyl)methanone, ... (5 entities in total)
• Functional Keywords: fatty acid synthase, human fas, keto-reductase, transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 147010.77

Authors

Toms, A.V.,Martin, M.W. (deposition date: 2019-01-14, release date: 2019-02-20, Last modification date: 2024-11-06)

Primary citation

Martin, M.W.,Lancia Jr., D.R.,Li, H.,Schiller, S.E.R.,Toms, A.V.,Wang, Z.,Bair, K.W.,Castro, J.,Fessler, S.,Gotur, D.,Hubbs, S.E.,Kauffman, G.S.,Kershaw, M.,Luke, G.P.,McKinnon, C.,Yao, L.,Lu, W.,Millan, D.S.
Discovery and optimization of novel piperazines as potent inhibitors of fatty acid synthase (FASN).
Bioorg. Med. Chem. Lett., 29:1001-1006, 2019

PubMed 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.

PubMed: 30803804
DOI: 10.1016/j.bmcl.2019.02.012

Experimental method

X-RAY DIFFRACTION (2.26 Å)