Leveraging on Active Site Similarities; Identification of Potential Inhibitors of Zinc-Finger and UFSP domain Protein (ZUFSP).

Leveraging on Active Site Similarities; Identification of Potential Inhibitors of Zinc-Finger and UFSP domain Protein (ZUFSP). Curr Pharm Biotechnol. 2020 Jul 30;: Authors: Ajadi MB, Soremekun OS, Adewumi AT, Kumalo HM, Soliman MES Abstract ZUFSP (Zinc-finger and UFSP domain protein) is a novel representative member of the recently characterized seventh class of Deubiquitinating Enzymes (DUBs). Due to the roles DUBs play in genetic instability, they have become a major drug target in cancer and neurodegenerative diseases. ZUFSP, being a DUB enzyme has also been implicated in genetic instability. However, no inhibitor has been developed to target ZUFSP. Therefore, in this study, we used a combined drug repurposing, virtual screening and per-Residue Energy Decomposition (PRED) to identify ZUFSP inhibitors with therapeutic potential. 3-bromo-6-{[4-hydroxy-1-3(3-phenylbutanoyl) piperidin-4-yl]methyl}-4H,5H,6H,7H-thieno[2,3- C]pyridine-7-one (BHPTP) which is an inhibitor of USP7 was repurposed to target ZUFSP. The rationale behind this is based on the similarity of the active between USP7 and ZUFSP. PRED of the binding between BHPTP and ZUFSP revealed Cys223, Arg408, Met410, Asn460, and Tyr465 as the crucial residues responsible for this interaction. The pharmacophoric moieties of BHPTP responsible for this binding along with other physiochemical properties were used as a filter to retrieve potential ligands. 799 compounds were retrieved,...
Source: Current Pharmaceutical Biotechnology - Category: Biotechnology Authors: Tags: Curr Pharm Biotechnol Source Type: research