Science News

Combined Ligand-Based and Structure-Based Virtual Screening Approach for Identification of New Dipeptidyl Peptidase 4 Inhibitors.

A new interesting article has been published in Curr Drug Discov Technol. 2018 Sep 26. doi: 10.2174/1570163815666180926111558. and titled:

Combined Ligand-Based and Structure-Based Virtual Screening Approach for Identification of New Dipeptidyl Peptidase 4 Inhibitors.

Authors of this article are:
Upadhyay J Gajjar A Suhagia BN.

A summary of the article is shown below:
BACKGROUND: Dipeptidyl Peptidase 4 (DPP 4) enzyme cleaves an incretin based glucoregulatory hormone Glucagon Like Peptide -1 from N-terminal where penultimate amino acid is either alanine or proline. Several DPP 4 inhibitors, “gliptins”, are approved for management of Type 2 Diabetes or under clinical trial. In present study, combined pharmacophore and docking based virtual screening protocol was used for identification of new hits from the Specs Database, which would inhibit DPP 4.METHODS: The entire computational studies were performed using the Discovery Studio v. 4.1 software package, Pipeline Pilot v. 9.2 (Accelrys Inc.) and FRED v. 2.2.5 (OpenEye Scientific Software). Common feature pharmacophore model was generated from known DPP 4 inhibitors and validated by Receiver Operating curve analysis and GH-scoring method. Database search of Specs commercial database was performed using validated pharmacophore. Hits obtained from pharmacophore search were further docked into binding site of DPP 4. Based on analysis of docked poses of hits, 10 compounds were selected for in- vitro DPP 4 enzyme inhibition assay.RESULTS: Based on docking studies, virtual hits were predicted to form interaction with essential amino acid residues of DPP 4 and have almost similar binding orientation as that of reference molecule. Three compounds having Specs database ID- AN-465/42837213, AP-064/42049348 and AN-465/43369427 were found to inhibit DPP 4 enzyme moderately.CONCLUSION: The present study demonstrates a successful utilization of in-silico tools in identification of new DPP 4 inhibitor, which can serve as starting point for the development of novel DPP4 inhibitors.Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Check out the article’s website on Pubmed for more information:



This article is a good source of information and a good way to become familiar with topics such as: DPP 4;Gliptins;Molecular Docking ;Pharmacophore;Specs Database;Virtual Screening.

Categories: Science News