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PDBsum entry 5m0s
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References listed in PDB file
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Key reference
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Title
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Rational design of autotaxin inhibitors by structural evolution of endogenous modulators.
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Authors
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W.J.Keune,
F.Potjewyd,
T.Heidebrecht,
F.Salgado-Polo,
S.J.Macdonald,
L.Chelvarajan,
A.Abdel latif,
S.Soman,
A.J.Morris,
A.J.Watson,
C.Jamieson,
A.Perrakis.
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Ref.
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J Med Chem, 2017,
60,
2006-2017.
[DOI no: ]
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PubMed id
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Abstract
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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.
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