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Target intelligence / Profile preview
Transcription activator BRG1 (SMARCA4) (BRG1)
- Target
- BRG1
- Molecular classification
- Transcription factor, Enzyme
01
Overview
SMARCA4 encodes the BRG1 protein, a core ATPase subunit of the SWI/SNF chromatin remodeling complex that regulates gene expression by altering chromatin structure, with helicase and ATPase activities; it acts as a tumor suppressor involved in DNA repair, replication, and cell proliferation control, but mutations lead to deficiency in various cancers including lung cancer, thoracic sarcomas, medulloblastoma, and rhabdoid tumors
- Other names
- ATP-dependent chromatin remodeler SMARCA4SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4BAF190ASNF2BSNF2L4
02
Mechanism of action
Synthetic lethality targeting SMARCA2 or DNA damage repair pathways in deficient tumors, Epigenetic modulation via Polycomb group protein inhibition, Immune checkpoint blockade exploiting MSI-H/dMMR/TMB-H phenotypes
03
Biological functions
Chromatin remodelingGene expression regulationDNA repairGenome replicationCell growth and division control
04
Disease associations
CancerCoffin-Siris syndrome
05
Safety considerations
Poor prognosis with SMARCA4 mutationsLimited responsiveness to surgery/chemotherapy/immunotherapy/targeted therapiesCo-mutations (e.g., STK11/KEAP1) worsen outcomes under chemo-immunotherapyChallenges in developing direct inhibitors due to unique molecular characteristics
06
Interacting drugs
Immune checkpoint inhibitors
7 more in the full profile.
07
Biomarkers
SMARCA4 deficiency/mutation statusNeuron-specific enolase (NSE) elevation in SMARCA4-deficient undifferentiated thoracic tumorsMicrosatellite instability-high (MSI-H)Deficient mismatch repair (dMMR)High tumor mutation burden (TMB-H)
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