G-141

G-141 is a preclinical, orally administered small-molecule inhibitor of SMARCA2 (SWI/SNF related, matrix associated, actin-dependent regulator of chromatin, subfamily a, member 2) developed by Onco3R Therapeutics. The drug is designed to treat cancers harboring loss-of-function mutations in SMARCA4 (BRG1), such as a subset of non-small cell lung cancers (NSCLC), by exploiting a synthetic lethal relationship between the two paralogs. In SMARCA4-deficient cells, the SWI/SNF chromatin-remodeling complex becomes entirely dependent on SMARCA2 for its function; G-141 selectively inhibits SMARCA2 to induce cell death in these tumor cells while sparing normal tissues. It boasts sub-nanomolar potency and over 35-fold selectivity against SMARCA4, a feature intended to avoid the safety concerns and toxicities observed with previous dual SMARCA4/2 inhibitors. G-141 has demonstrated robust anti-tumor activity in xenograft models and is progressing toward IND-enabling studies anticipated in mid-2026.