PROTAC SMARCA2 degrader-35 (Compound 43) is a selective SMARCA2 PROTAC degrader with a DC50 < 0.1 μM for SMARCA2. PROTAC SMARCA2 degrader-35 has anticancer activity and regulates cancer cell proliferation and growth through cell cycle arrest and DNA replication inhibition in SMARCA4-deleted cancer cells [1] [2]. (Pink: SMARCA2 Target protein ligand; Blue: E3 ligase ligand; Black: linker).
In Vitro, SMARCA2 and SMARCA4 are the core catalytic subunits of the SWUSNF complexes, which play an important role in controlling gene expression by remodeling chromatin. SMARCA4 is mutated in multiple cancers and SMARCA4 -deficient cancer cells can become highly dependent on SMARCA2 for their survival. Therefore, targeting SMARCA2 in SMARCA4 -del eted cancers using selective SMARCA2 degraders induces synthetic lethality, while sparing SMARCA4 wild-type normal cells.
References:
[1]. Corey H B, et al. BRM Targeting Compounds And Associated Methods Of Use. US20240165244A1. 2024-05-23.
[2]. Ito K, et al. Combination treatment regimens - smarca2 degrader with taxane anticancer agent. WO2025194059A1. 2025-09-18.
In Vitro, SMARCA2 and SMARCA4 are the core catalytic subunits of the SWUSNF complexes, which play an important role in controlling gene expression by remodeling chromatin. SMARCA4 is mutated in multiple cancers and SMARCA4 -deficient cancer cells can become highly dependent on SMARCA2 for their survival. Therefore, targeting SMARCA2 in SMARCA4 -del eted cancers using selective SMARCA2 degraders induces synthetic lethality, while sparing SMARCA4 wild-type normal cells.
References:
[1]. Corey H B, et al. BRM Targeting Compounds And Associated Methods Of Use. US20240165244A1. 2024-05-23.
[2]. Ito K, et al. Combination treatment regimens - smarca2 degrader with taxane anticancer agent. WO2025194059A1. 2025-09-18.