Identification of Novel Structurally Diverse Anaplastic Lymphoma Kinase Inhibitors Based on Pharmacophore Modeling, Virtual Screening and Molecular Docking.

Identification of Novel Structurally Diverse Anaplastic Lymphoma Kinase Inhibitors Based on Pharmacophore Modeling, Virtual Screening and Molecular Docking.
Comb Chem High Throughput Screen. 2016 Aug 1;
Authors: You R, Zhou L, Zhong L, Li X, Zhou S, Tian Y
Abstract
Anaplastic lymphoma kinase, an insulin receptor protein-tyrosine kinase, is a very attractive receptor protein target for anticancer therapy. Pharmacophore hypotheses modeling, virtual screening and molecular docking were used to detect potential inhibitors of anaplastic lymphoma kinase in this paper. After the generation of ten pharmacophore hypotheses, Hypo1 with the highest correlation value (0.981), lowest RMS (0.565), highest cost difference (83.850) along with four typical chemical features was regarded as the best hypothesis. Hypo1 contains a hydrogen bond acceptor, a hydrogen bong donor, a hydrophobic and a ring aromatic feature. And then, hypo1 was validated and used to screen three databases after screened by Lipinski's rule of five. 3015 hits screened by Hypo1 were submitted to molecular docking based on the crystal structure of anaplastic lymphoma kinase. Ultimately, 7 molecules with four different scaffolds were selected as potential leads for designing the anaplastic lymphoma kinase inhibitors.
PMID: 27487788 [PubMed - as supplied by publisher]

Source: Combinatorial Chemistry and High Throughput Screening - July 31, 2016 Category: Chemistry Authors: You R, Zhou L, Zhong L, Li X, Zhou S, Tian Y Tags: Comb Chem High Throughput Screen Source Type: research