Description
Use PFI-3 to inhibit the bromodomains (IC50 = 89 nM) of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member (SMARCA2) and SMARCA4, disrupting their functions in gene regulation. Also known as BRM and BRG1, SMARCA2 and SMARCA4 are catalytic ATPases in the SWI/SNF chromatin-remodeling complex, and they have been associated with regulating genes for stem cell maintenance and lineage specification (Fedorov et al. Sci Adv, 2015). Bromodomains bind to acetylated lysine residues in histone tails to recruit transcriptional complexes which are involved in DNA damage repair (Filippakopoulos & Knapp. Nat Rev Drug Discov, 2014). By inhibiting SWI/SNF chromatin binding, PFI-3 can enhance the effectiveness of DNA-damaging chemotherapeutics on cancer cells (Pérez-Salvia & Esteller. Epigenetics, 2017).
PFI-3 has been used for:
DIFFERENTIATION
· Reduce stemness and deregulate lineage specification in mouse embryonic stem cells and enhance differentiation of trophoblast stem cells (Fedorov et al. Sci Adv, 2015).
· Decrease the fusion index of mouse myoblasts and reduce skeletal muscle regeneration after injury in a mouse model (Sharma et al. Nucleic Acids Res, 2021).
CANCER RESEARCH
· Sensitize human lung, colorectal, and osteosarcoma cancer cells to DNA damage caused by chemotherapeutics by blocking chromatin binding of bromodomains (Lee et al. Mol Cancer Res, 2021).
· Enhance anti-cancer effects of temozolomide on human glioblastoma cells and glioblastoma mouse models (Yang et al. Pharmaceuticals (Basel), 2021).
