Repurposing of the CDK inhibitor PHA-767491 as a NRF2 inhibitor drug candidate for cancer therapy via redox modulation.

ABSTRACT: Oxidative stress and cellular response mechanisms such as NRF2-mediated antioxidant responses play differential roles in healthy and diseased cells. Constant generation and elimination of high levels of reactive oxygen species is a hallmark of many cancer cell types; this phenomenon is not observed during steady state of healthy cells. Manipulation of NRF2 transcriptional activity and the cellular redox homeostasis therefore has potential to be therapeutically exploitable for cancer therapy by preferentially targeting cancer cells for induction of oxidative stress. We found that the NRF2 inhibitor brusatol triggered increased oxidative stress while compromising viability and proliferation of multiple myeloma cells. Using a repurposing approach we discovered that the Cdc7/CDK9 inhibitor PHA

SUBMITTER: Liu HY 

PROVIDER: S-EPMC9547662 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature