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The Identification of New CD38 Inhibitors by Combined Structure and Ligand Based Virtual Screening Approaches of ZINC Database

[ Vol. 15 , Issue. 6 ]

Author(s):

Bakhtyar Sepehri and Raouf Ghavami*   Pages 654 - 660 ( 7 )

Abstract:


Background: Cluster of differentiation 38 (CD38) is major NADase and regulates the intracellular level of NAD. It uses NAD as substrate to produce ADP Ribose (ADPR) and cyclic ADP ribose (cADPR) and converts NADP to NAADP. Its inhibition can be utilized to treat several condition.

Methods: In this research, for identifying new potent CD38 inhibitors both structure and ligand based virtual screening approaches were used to search 1,064,166 and 23,129,083 clean compounds, respectively. Both Structure Based Virtual Screening (SBVS) and Ligand Based Virtual Screening (LBVS) approaches were performed in istar website.

Results: Based on SBVS and LBVS results, 53 and 20 molecules, respectively, were selected. In next step iGEMDOCK software was used to dock these 73 molecules to the NMN binding site of CD38 and finally 7 molecules were selected. For more validation of iGEMDOCK software results, AutoDock software was used to dock these 7 molecules to the NMN binding site of CD38. Auto- Dock results indicated only 5 molecules of these 7 molecules can be considered as CD38 inhibitors. These compounds are zinc68054028, zinc78782163, zinc63259986, zinc34792490 and zinc63260004.

Conclusion: SBVS and LBVS are useful tools to identify new CD38 inhibitors with greater activity.

Keywords:

CD38 inhibitors, virtual screening, LBVS, SBVS, molecular docking, binding site.

Affiliation:

Department of Chemistry, Faculty of Science, University of Kurdistan, P. O. Box 416, Sanandaj, Department of Chemistry, Faculty of Science, University of Kurdistan, P. O. Box 416, Sanandaj

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