Discovery of highly selective inhibitors of human fatty acid binding protein 4 (FABP4) by virtual screening

Compound 1 was identified as an inhibitor of human FABP4 with an IC50 of 13.5μM and it showed a selectivity more than 144-fold over human FABP3. In this study, a series of small molecule inhibitors of human FABP4 were identified through virtual screening. Compound 1 is the most potent hit against FA...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2010-06, Vol.20 (12), p.3675-3679
Hauptverfasser: Cai, Haiyan, Yan, Guirui, Zhang, Xiaodong, Gorbenko, Olena, Wang, Heyao, Zhu, Weiliang
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Sprache:eng
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Zusammenfassung:Compound 1 was identified as an inhibitor of human FABP4 with an IC50 of 13.5μM and it showed a selectivity more than 144-fold over human FABP3. In this study, a series of small molecule inhibitors of human FABP4 were identified through virtual screening. Compound 1 is the most potent hit against FABP4 with a selectivity of more than 144-fold preferences over human FABP3. In addition, MD simulation and mutation studies revealed key residues for inhibitory potency and selectivity, which provides a guideline for further drug design against obesity, diabetes and atherosclerosis.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2010.04.095