GSK3326595
PRMT5 inhibitor / GSK3326595 is a potent (IC50 = 6.2nM), selective (>4000-fold over 20 other methyltransferases), SAM uncompetitive, peptide competitive inhibitor of PRMT5.1 PRMT5 inhibition activated the p53 pathway via induction of alternative splicing of MDM4 leading to a potent anti-proliferative response both in vitro and in vivo. Combination therapy with palbociclib (CDK4/6 inhibitor, Focus Cat.# 10-4760) and GSK3326595 lead to increased efficacy of palbociclib in treating native and resistant models of melanoma via regulation of the PRMT5-MDM4 axis.2 Currently in clinical Trials.3
Biochemicals & reagents
1616392-22-3
EPZ015938
1) Gerhart et al. (2018), Activation of the p53-MDM4 regulatory axis defines the anti-tumor response to PRMT5 inhibition through its role in regulating cellular splicing; Sci. Rep. 8 9711 2) AbuHammad et al. (2019), Regulation of PRMT5-MDM4 axis is critical in the response to CDK4/6 inhibitors in melanoma; Proc. Natl. Acad. Sci. USA 116 179909 3) NCT02783300
-20°C
TARGET: Protein methyltransferase; RNA -- PATHWAY: p53; Chromatin; Posttranslational modification; Proliferation -- RESEARCH AREA: Epigenetics -- DISEASE AREA: Cancer