Molecules, Vol. 23, Pages 453: Identification of Novel Protein Kinase Receptor Type 2 Inhibitors Using Pharmacophore and Structure-Based Virtual Screening

In this study, a pharmacophoric model based on the crystallographic pose of ponatinib, a potent RIPK2 inhibitor, and 30 other ones selected from the BindingDB repository database, was built. Compounds were selected based on the available ZINC compounds database and in silico predictions of their pharmacokinetic, toxicity and potential biological activity. Molecular docking was performed to identify the probable interactions of the compounds as well as their binding affinity with RIPK2. The compounds were analyzed to ponatinib and WEHI-345, which also used as a control. At least one of the compounds exhibited suitable pharmacokinetic properties, low toxicity and an interesting binding affinity and high fitness compared with the crystallographic pose of WEHI-345 in complex with RIPK2. This compound also possessed suitable synthetic accessibility, rendering it a potential and very promising RIPK2 inhibitor to be further investigated in regards to different diseases, particularly inflammatory ones.

Source: Molecules - February 18, 2018 Category: Chemistry Authors: Josiane Cruz Moys és Neto Luciane Silva Ryan da S. Ramos Josivan da S. Costa Davi Brasil Cleison Lobato Glauber da Costa Jos é Bittencourt Carlos da Silva Franco Leite Cleydson Santos Tags: Article Source Type: research