Targeting Wnt-driven cancers: Discovery of novel tankyrase inhibitors

Eur J Med Chem. 2017 Dec 15:142:506-522. doi: 10.1016/j.ejmech.2017.09.030. Epub 2017 Oct 7.


Recent years have seen substantially heightened interest in the discovery of tankyrase inhibitors (TNKSi) as new promising anticancer agents. In this framework, the aim of this review article is focused on the description of potent TNKSi also endowed with disruptor activity toward the Wnt/β-catenin signaling pathway. Beginning with an overview of the most characterized TNKSi deriving from several drug design approaches and classifying them on the basis of the molecular interactions with the target, we discuss only those ones acting against Wnt cancer cell lines. In addition, comprehensive structure property relationships (SPR) emerging from the hit evolution processes and preclinical results are provided. We then review the most promising TNKSi hitherto reported in literature, acting in vivo models of Wnt-driven cancers. Some outlooks on current issues and future directions in this field are also discussed.

Keywords: PARP family; Tankyrase inhibitors; Wnt pathway disruption; Wnt-driven cancers; Wnt/β-catenin signaling pathway.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Drug Discovery* / methods
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Molecular Targeted Therapy / methods
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Tankyrases / antagonists & inhibitors*
  • Tankyrases / metabolism
  • Wnt Signaling Pathway / drug effects*


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Tankyrases