2. Academic Validation
  3. NMR structure of a potent small molecule inhibitor bound to human keratinocyte fatty acid-binding protein

NMR structure of a potent small molecule inhibitor bound to human keratinocyte fatty acid-binding protein

  • J Med Chem. 2006 Aug 10;49(16):5013-7. doi: 10.1021/jm060360i.
Patricia A McDonnell 1,  Keith L Constantine,  Valentina Goldfarb,  Stephen R Johnson,  Richard Sulsky,  David R Magnin,  Jeffrey A Robl,  Thomas J Caulfield,  Rex A Parker,  David S Taylor,  Leonard P Adam,  William J Metzler,  Luciano Mueller,  Bennett T Farmer 2nd
Affiliations

Affiliation

  • 1 Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 4000, Princeton, New Jersey 08543, USA. patricia.mcdonnell@bms.com
PMID: 16884313 DOI: 10.1021/jm060360i
Abstract

The NMR structure is presented for compound 1 (BMS-480404) (Ki = 33 (+/-2) nM) bound to keratinocyte fatty acid-binding protein. This article describes interactions between a high affinity drug-like compound and a member of the fatty acid-binding protein family. A benzyl group ortho to the mandelic acid in 1 occupies an area of the protein that fatty acids do not normally contact. Similar to that in the kFABP-palmitic acid structure, the acid moiety in 1 is proximal to R129 and Y131. Computational modeling indicates that the acid moiety in 1 interacts indirectly via a modeled water molecule to R109.

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