GNE-375 (GNE375) is a potent, selective BRD9 inhibitor with IC50 of 5 nM, displays >480-fold selectivity over BRD4, CECR2, and TAF1.
GNE-375 decreases BRD9 binding to chromatin, and decreases expression of ALDH1A1, a gene previously shown to be important in drug tolerance.
GNE-375 shows remarkable potency in preventing the emergence of a drug tolerant population in EGFR mutant PC9 cells treated with EGFR inhibitors.
