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SMARCA2 selective degrader
- Development stage
- Preclinical
- Lead developer
- Foghorn Therapeutics
- Modality
- PROTACs (E3 ligase recruitment) → Targeted Protein Degraders (TPDs) → Small Molecules, Bivalent/Multivalent Binders → Multivalent & Scaffold-Based Small Molecules → Small Molecules
- Administration
- Oral, Intravenous
01
Overview
The SMARCA2 selective degrader is an investigational protein degrader being developed by Foghorn Therapeutics to treat cancers characterized by SMARCA4 (BRG1) mutations. Utilizing the company's Gene Traffic Control® platform, this agent is designed to selectively induce the degradation of SMARCA2 (BRM), a paralog of SMARCA4 and a critical component of the BAF (SWI/SNF) chromatin remodeling complex. In tumors where SMARCA4 is lost or mutated, the cells become uniquely dependent on SMARCA2 for the maintenance of chromatin structure and gene expression, a relationship known as synthetic lethality. By targeting SMARCA2 for degradation, the drug aims to selectively eliminate cancer cells while sparing healthy cells that retain functional SMARCA4. This program is currently in the early stages of development for indications such as SMARCA4-mutated non-small cell lung cancer (NSCLC) and other SMARCA4-deficient malignancies.
- Other names
- Selective SMARCA2 degraderSMARCA2 protein degraderSMARCA-2 protein degraderSMARCA 2 protein degrader
02
Targets
SMARCA2 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily A member 2)CRBN (Cereblon)SMARCA4 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4)PBRM1 (Protein polybromo-1)
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