SMARCA2 Degrader PLX-61639

**Semantic type:** Pharmacologic Substance

**Definition:** An orally bioavailable monovalent direct degrader of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2 (SMARCA2; BRM), with potential antineoplastic activity. Upon oral administration, SMARCA2 degrader PLX-61639 specifically targets and binds to SMARCA2, induces interactions with the E3 ubiquitin ligase DCAF16, and forms a ternary complex. This induces E3 ligase ubiquitination and proteasome-mediated degradation of SMARCA2. This may lead to the inhibition of the SWI/SNF (BRG1/BRM-associated factor; BAF) chromatin remodeling complex, which disrupts chromatin remodeling and gene expression. This results in the downregulation of oncogenic pathways and the inhibition of tumor cell proliferation in SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 (SMARCA4; BRG1)-deleted cancers. SMARCA2 and SMARCA4 are the primary ATPase components and mutually exclusive core catalytic subunits of the SWI/SNF chromatin remodeling complex, an important regulator of transcriptional programs and gene expression. SMARCA4 expression is absent in certain cancer cells, and these SMARCA4-deleted cancer cells depend on SMARCA2 for survival.

**Synonyms:** - PLX 61639 - PLX-61639 - PLX61639 - SMARCA2 Monovalent Direct Degrader PLX-61639 - SMARCA2 Protein Degrader PLX-61639