Zoning in on Tankyrases: A Brief Review on the Past, Present and Prospective Studies.

Abstract:

BACKGROUND:Tankyrases are known for their multifunctionalities within the poly(ADPribose) polymerases family and playing vital roles in various cellular processes which include the regulation of tumour suppressors. Tankyrases, which exist in two isoforms; Tankyrase 1 and 2, are highly homologous and an integral part of the Wnt β -catenin pathway that becomes overly dysregulated when hijacked by pro-carcinogenic machineries. METHODS:In this review, we cover the distinct roles of the Tankyrase isoforms and their involvement in the disease pathogenesis. Also, we provide updates on experimentally and computationally derived antagonists of Tankyrase whilst highlighting the precedence of integrative computer-aided drug design methods towards the discovery of selective inhibitors. RESULTS:Despite the high prospects embedded in the therapeutic targeting and blockade of Tankyrase isoforms, the inability of small molecule inhibitors to achieve selective targeting has remained a major setback, even until date. This explains numerous incessant drug design efforts geared towards the development of highly selective inhibitors of the respective Tankyrase isoforms since they mediate distinct aberrancies in disease progression. Therefore, considering the setbacks of conventional drug design methods, can computer-aided approaches actually save the day? CONCLUSION:The implementation of computer-aided drug design techniques in Tankyrase research could help complement experimental methods and facilitate ligand/structure-based design and discovery of small molecule inhibitors with enhanced selectivity.

authors

Peters XQ,Malinga TH,Agoni C,Olotu FA,Soliman MES

doi

10.2174/1871520619666191019114321

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

1920-1934

issue

16

eissn

1871-5206

issn

1875-5992

pii

ACAMC-EPUB-101659

journal_volume

19

pub_type

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