Pharmacophore-based 3D-QSAR modeling, Virtual Screening and Molecular Docking Analysis for the Detection of MERTK Inhibitors with Novel Scaffold.

In this study, 107 MERTK inhibitors with known activities were gathered to generate a ligand-based pharmacophore model (ADDHH.4), followed by building a 3D-QSAR model, which had high value of coefficient of determination (R2=0.9061) and high value of coefficient of determination (Q2=0.7442). For the pharmacophore model, two hydrogen bond donors (D), one hydrogen bond receptor (A), and two hydrophobic groups (H) were considered as the key elements contributing to ligand activity. The model then served to search a drug-like database with 1.5 million molecules, and 47832 hits were obtained. Subsequently, docking procedure was applied on these hits, and 840 compounds were obtained through high-throughput virtual screening (HTVS). Standard precision (SP), extra precision (XP) and rule of five were also used in virtual screening protocol. Finally, six candidates were identified as potential MERTK inhibitors, with the docking mode in MERTK analyzed.
PMID: 26673902 [PubMed - as supplied by publisher]

Source: Combinatorial Chemistry and High Throughput Screening - December 16, 2015 Category: Chemistry Authors: Zhou S, Zhou L, Cui R, Tian Y, Li X, You R, Zhong L Tags: Comb Chem High Throughput Screen Source Type: research