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

Haiyan Cai, Guirui Yan, Xiaodong Zhang, Olena Gorbenko, Heyao Wang, Weiliang Zhu

a b s t r a c t

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.