ACBI2

ACBI2 is a potent, orally bioavailable, VHL-recruiting proteolysis-targeting chimera (PROTAC) that preferentially degrades the chromatin remodeler SMARCA2 (also known as BRM) while also degrading PBRM1, with strong selectivity over the closely related paralogue SMARCA4 in cellular and ex vivo human whole blood assays.[3][5][6] Designed by Boehringer Ingelheim using structure- and property-guided optimization of VHL-based degraders, ACBI2 achieves low-nanomolar SMARCA2 degradation (DC50 ≈ 1 nM in RKO cells) and demonstrates in vivo antitumor activity in SMARCA4-deficient non–small cell lung cancer xenograft models, enabling pharmacologic evaluation of synthetic lethality based on SMARCA2 dependency in SMARCA4-deficient cancers.[1][3][5][6] It is broadly used as a chemical probe tool compound to study BAF (SWI/SNF) complex biology and SMARCA2-targeted protein degradation, and is currently characterized as a preclinical research agent rather than a clinical drug.[3][4][6]