Insights of tankyrases: A novel target for drug discovery

Eur J Med Chem. 2020 Dec 1:207:112712. doi: 10.1016/j.ejmech.2020.112712. Epub 2020 Aug 17.

Abstract

Tankyrases are the group of enzymes belonging to a class of Poly (ADP-ribose) polymerase (PARP) recently named ADP-ribosyltransferase (ARTD). The two isoforms of tankyrase i.e. tankyrase1 (TNKS1) and tankyrase2 (TNKS2) were abundantly expressed in various biological functions in telomere regulation, Wnt/β-catenin signaling pathway, viral replication, endogenous hormone regulation, glucose transport, cherubism disease, erectile dysfunction, and apoptosis. The structural analysis, mechanistic information, in vitro and in vivo studies led identification and development of several classes of tankyrase inhibitors under clinical phases. In the nutshell, this review will drive future research on tankyrase as it enlighten the structural and functional features of TNKS 1 and TNKS 2, different classes of inhibitors with their structure-activity relationship studies, molecular modeling studies, as well as past, current and future perspective of the different class of tankyrase inhibitors.

Keywords: Anticancer; Antidiabetic; Antiviral; Clinical phases and inhibitors; Dysplasia; Hormonal; Tankyrases.

Publication types

  • Review

MeSH terms

  • Animals
  • Catalytic Domain / drug effects
  • Drug Development
  • Drug Discovery*
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Isoenzymes / analysis
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Models, Molecular
  • Protein Conformation / drug effects
  • Tankyrases / analysis
  • Tankyrases / antagonists & inhibitors*
  • Tankyrases / metabolism*

Substances

  • Enzyme Inhibitors
  • Isoenzymes
  • Tankyrases