3ANT

Human soluble epoxide hydrolase in complex with a synthetic inhibitor

Summary for 3ANT

• Entry DOI: 10.2210/pdb3ant/pdb
• Related: 3ANS
• Descriptor: Epoxide hydrolase 2, 4-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-N-[(1S,2R)-2-phenylcyclopropyl]piperidine-1-carboxamide (3 entities in total)
• Functional Keywords: hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P34913
• Total number of polymer chains: 2
• Total formula weight: 78001.74

Authors

Chiyo, N.,Ishii, T.,Hourai, S.,Yanagi, K. (deposition date: 2010-09-08, release date: 2011-01-19, Last modification date: 2023-11-01)

Primary citation

Tanaka, D.,Tsuda, Y.,Shiyama, T.,Nishimura, T.,Chiyo, N.,Tominaga, Y.,Sawada, N.,Mimoto, T.,Kusunose, N.
A practical use of ligand efficiency indices out of the fragment-based approach: ligand efficiency-guided lead identification of soluble epoxide hydrolase inhibitors
J.Med.Chem., 54:851-857, 2011

PubMed Abstract: Ligand efficiency is frequently used to evaluate fragment compounds in fragment-based drug discovery. We applied ligand efficiency indices in a conventional virtual screening-initiated lead generation study of soluble epoxide hydrolase inhibitors. From a considerable number of screening hits, we carefully selected a compound exhibiting relatively weak inhibitory activity but high ligand efficiency. This ligand efficiency-guided selection could reveal compounds possessing preferable lead-like characteristics in terms of molecular size and lipophilicity. The following hit-to-lead medicinal chemistry campaign successfully led to a more potent, ADMET-clean, lead-like compound preserving high ligand efficiency. Retrospective analyses, including consideration of the more recently proposed indices of ligand efficiency, shed light on the validity of our hit triage and hit-to-lead studies. The present work proposes a practical methodology for lead generation using the concept of ligand efficiency.

PubMed: 21192659
DOI: 10.1021/jm101273e

Experimental method

X-RAY DIFFRACTION (2.4 Å)