Efficient identification of new small molecules targeting succinate dehydrogenase in non-small cell lung cancer.

ABSTRACT:

Background

Lung cancer treatment efficacy remains a challenge due to limited therapeutic targets. Succinate dehydrogenase (SDH) enzyme, a crucial enzyme linking the citric acid cycle and the electron transport chain, is implicated in cancer metabolism. While existing compounds target metabolic diseases in vitro, SDH-targeted therapy for lung cancer remains elusive.

Methods

We assessed SDH expression levels in non-small cell lung (NSCLC) tissues and cell lines. Leveraging AtomNet® technology for compound identification, coupled with mitochondria- and cell-based enzyme activity assays, we discovered new SDH inhibitors. Using 2D monolayer, 3D organoid culture, and assays for cell viability, migration, mitochondrial reactive oxygen species, oxygen consumption rate, succinate acc

SUBMITTER: Silva L 

PROVIDER: S-EPMC12535061 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature