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Review
. 2024 Mar;28(3):117-130.
doi: 10.1080/14728222.2024.2317900. Epub 2024 Feb 14.

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

Lang Pan  1 , Istvan Boldogh  1
Affiliations
Review

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

Lang Pan et al. Expert Opin Ther Targets. 2024 Mar.

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.

Keywords: Epigenetic regulation; NF-κB; OGG1 inhibitor; airway remodeling; chronic lung inflammation.

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Conflict of interest statement

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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