The potential for OGG1 inhibition to be a therapeutic strategy for pulmonary diseases

Lang Pan, Istvan Boldogh

Research output: Contribution to journalReview articlepeer-review

Abstract

Introduction: Pulmonary diseases impose a daunting burden on healthcare systems and societies. Current treatment approaches primarily address symptoms, underscoring the urgency for the development of innovative pharmaceutical solutions. A noteworthy focus lies in targeting enzymes recognizing oxidatively modified DNA bases within gene regulatory elements, given their pivotal role in governing gene expression. Areas covered: This review delves into the intricate interplay between the substrate-specific binding of 8-oxoguanine DNA glycosylase 1 (OGG1) and epigenetic regulation, with a focal point on elucidating the molecular underpinnings and their biological implications. The absence of OGG1 distinctly attenuates the binding of transcription factors to cis elements, thereby modulating pro-inflammatory or pro-fibrotic transcriptional activity. Through a synergy of experimental insights gained from cell culture studies and murine models, utilizing prototype OGG1 inhibitors (O8, TH5487, and SU0268), a promising panorama emerges. These investigations underscore the absence of cytotoxicity and the establishment of a favorable tolerance profile for these OGG1 inhibitors. Expert opinion: Thus, the strategic targeting of the active site pocket of OGG1 through the application of small molecules introduces an innovative trajectory for advancing redox medicine. This approach holds particular significance in the context of pulmonary diseases, offering a refined avenue for their management.

Original languageEnglish (US)
JournalExpert Opinion on Therapeutic Targets
DOIs
StateAccepted/In press - 2024
Externally publishedYes

Keywords

  • airway remodeling
  • chronic lung inflammation
  • Epigenetic regulation
  • NF-κB
  • OGG1 inhibitor

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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