PFI 3 is a potent and selective inhibitor of polybromo 1 and SMARCA4 with Kd values of 48 and 89 nM, respectively [1].
Transcription activator BRG1 (SMARCA4) is a member of the SWI/SNF family and regulates transcription. Protein polybromo-1 (PB1, PBRM1) is a BRG1-associated factor and tumor suppressor.
PFI 3 is a potent and selective inhibitor of polybromo 1 and SMARCA4. PFI 3 bound to SMARCA2 and SMARCA4 bromodomains with Kd values of 55 and 110 nM, respectively. PFI-3 (2 μM) inhibited PBRM1 by 70%. In cell-based chromatin binding assays, PFI-3 replaced GFP-tagged SMARCA2 bromodomain in a dose-dependent way with IC50 value of 5.78 μM. PFI-3 was a cell-permeable probe suitable for studying SMARCA2/4 bromodomains. In the SMARCA4-deficient A549, H1299, H157 cell lines, PFI-3 had no anti-proliferative effects and was unable to replace SMARCA2 from chromatin. In THP-1 and MV4-11 leukemic cells, PFI 3 did not induce anti-cancer phenotype [1].
Reference:
[1]. Vangamudi B, Paul TA, Shah PK, et al. The SMARCA2/4 ATPase domain surpasses the bromodomain as a drug target in SWI/SNF mutant cancers: Insights from cDNA rescue and PFI-3 inhibitor studies. Cancer Res, 2015, pii: canres.3798.2015.