BRM014

SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily A member 2 (SMARCA2), also known as Brahma homologue (BRM), together with its close homologue Brahma-related gene 1 (BRG1), or SMARCA4, are ATPases of the large ATP-dependent SWI/SNF chromatin-remodeling complexes involved in transcriptional regulation of gene expression. BRM014 is an allosteric dual inhibitor of BRM and BRG1 (IC50<5 nM for both) [1]. It downregulated BRM-dependent gene expression and displayed antiproliferative activity in a BRG1-mutant-lung-tumor xenograft model after oral administration. Inhibition of BRG1/BRM ATPase by BRM014 inhibits chromatin openness [2]. For example, it reduced DNA accessibility to core regulatory factors (RUNX1, LM01 and MEIS1) at transcription factor PU.1 sites in AML cells [3]. P583 cells formed markedly large spheroids when treated with BRM014 [4].

References:

1) JPN Papillon et al. J. Med. Chem. 2018 61 10155

2) DC Hargreaves et al. Nat. Genet 2021 53:263

3) C Chambers et al. Cancer Res. 2023 83:983

4) AJ Krieg et al. Gynecol. Oncol. Rep. 2023 48 Supp 1:S32