Optimization of in silico designed fatty acid synthase modulators derived from the lead molecule orlistat

Abstract

Orlistat; or tetrahydrolipstatin has been found to have inhibitory effects on human Fatty Acid Synthase (hFASN), an enzyme overexpressed in many tumors responsible for energy upkeep and fatty acid synthesis. The crystalline structure of hFASN was used to extract Orlistat; analysis it’spharmacophoric moieties and generate a library using Orlistat as a scaffold to be utilized within a database for high throughput screening. Two distinct methods were used; and over 1,200 unique molecules have been generated, all compliant with Lipinski’s rule of 5.