Inhibitors of DNA glycosylases as prospective drugs

Grigory V. Mechetin, Anton V. Endutkin, Evgeniia A. Diatlova, Dmitry O. Zharkov

Research output: Contribution to journalReview articlepeer-review

4 Citations (Scopus)

Abstract

DNA glycosylases are enzymes that initiate the base excision repair pathway, a major biochemical process that protects the genomes of all living organisms from intrinsically and environmentally inflicted damage. Recently, base excision repair inhibition proved to be a viable strategy for the therapy of tumors that have lost alternative repair pathways, such as BRCA-deficient cancers sensitive to poly(ADP-ribose)polymerase inhibition. However, drugs targeting DNA glycosylases are still in development and so far have not advanced to clinical trials. In this review, we cover the attempts to validate DNA glycosylases as suitable targets for inhibition in the pharmacological treatment of cancer, neurodegenerative diseases, chronic inflammation, bacterial and viral infections. We discuss the glycosylase inhibitors described so far and survey the advances in the assays for DNA glycosylase reactions that may be used to screen pharmacological libraries for new active compounds.

Original languageEnglish
Article number3118
Number of pages30
JournalInternational Journal of Molecular Sciences
Volume21
Issue number9
DOIs
Publication statusPublished - 28 Apr 2020

Keywords

  • DNA glycosylases
  • DNA repair
  • Drug targets
  • ESCHERICHIA-COLI FPG
  • BASE-EXCISION-REPAIR
  • drug targets
  • PROINFLAMMATORY GENE-EXPRESSION
  • VACCINIA VIRUS
  • SENSITIVE DETECTION
  • PROCESSIVITY FACTOR
  • SMALL-MOLECULE INHIBITOR
  • SIGNAL AMPLIFICATION
  • SUBSTRATE-SPECIFICITY
  • PSEUDOMONAS-AERUGINOSA

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