| Literature DB >> 28165241 |
Willem-Jan Keune1, Frances Potjewyd2, Tatjana Heidebrecht1, Fernando Salgado-Polo1, Simon J F Macdonald3, Lakshman Chelvarajan4, Ahmed Abdel Latif4, Sony Soman4, Andrew J Morris4, Allan J B Watson2, Craig Jamieson2, Anastassis Perrakis1.
Abstract
Autotaxin produces the bioactive lipid lysophosphatidic acid (LPA) and is a drug target of considerable interest for numerous pathologies. We report the expedient, structure-guided evolution of weak physiological allosteric inhibitors (bile salts) into potent competitive Autotaxin inhibitors that do not interact with the catalytic site. Functional data confirms that our lead compound attenuates LPA mediated signaling in cells and reduces LPA synthesis in vivo, providing a promising natural product derived scaffold for drug discovery.Entities:
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Year: 2017 PMID： 28165241 DOI： 10.1021/acs.jmedchem.6b01743
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446