Probable global transcription activator SNF2L2 (SMARCA2) (SMARCA2)

SMARCA2 (Probable global transcription activator SNF2L2), also known as BRM, is a core catalytic subunit of the mammalian SWI/SNF (BAF) chromatin-remodeling complex [1, 12]. It functions as an ATP-dependent helicase that utilizes energy from ATP hydrolysis to reposition nucleosomes, thereby regulating DNA accessibility for transcription, replication, and repair [4, 12, 14]. SMARCA2 is highly homologous to its paralog SMARCA4 (BRG1), and the two subunits are mutually exclusive within the BAF complex [2, 5, 21]. In many cancers, such as non-small cell lung cancer (NSCLC) and esophageal carcinoma, SMARCA4 is frequently lost or mutated, creating a synthetic lethal dependency on SMARCA2 for cell survival [2, 10, 19]. Consequently, SMARCA2 has emerged as a high-priority therapeutic target, with drug development efforts focusing on selective ATPase inhibitors and targeted protein degraders (PROTACs) like PRT3789 [3, 10, 17]. These therapies aim to selectively eliminate SMARCA2 function in SMARCA4-deficient tumor cells while maintaining a therapeutic window by sparing normal tissues that retain functional SMARCA4 [18, 21].

Other names

BRMBrahma homologSNF2-alphaBAF190BNCBRShBRMSWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2

ATPase inhibition and targeted protein degradation (PROTAC)