wt-IDH1 small molecule inhibitor

A class of small molecule inhibitors designed to target the wild-type isoform of isocitrate dehydrogenase 1 (wt-IDH1). While most IDH1 inhibitors in clinical development target the mutant form (mIDH1), wt-IDH1 inhibitors are being investigated for their ability to modulate the tumor microenvironment, particularly in glioblastoma (GBM). Research from Northwestern University and Washington University in St. Louis has identified wt-IDH1 as a metabolic checkpoint in tumor-associated myeloid cells (TAMCs). Inhibition of wt-IDH1 in these cells reduces oxidative phosphorylation, inhibits myeloid cell proliferation, and promotes a tumoricidal inflammatory phenotype. This metabolic reprogramming increases CD8+ T cell infiltration and can overcome resistance to immune checkpoint therapies (ICT) such as PD-1 blockade. Brain-penetrant tool compounds like GSK602 (also known as IDH1-IN-1) have been used in preclinical studies to credential this therapeutic strategy as a novel immunotherapeutic approach for GBM.

Other names

wild-type IDH1 inhibitorwt-IDH1 inhibitorwt-IDH-1 inhibitorwt-IDH 1 inhibitorwt-IDH1-specific small molecule inhibitorwt-IDH-1-specific small molecule inhibitorwt-IDH 1-specific small molecule inhibitor