PF-06726304 acetate

PF-06726304 acetate is a potent and selective EZH2 inhibitor. PF-06726304 acetate inhibits wild-type and Y641N mutant EZH2 with Kis of 0.7 and 3.0 nM, respectively. PF-06726304 acetate displays robust antitumor growth activity[1].

Research Areas >> Cancer

Signaling Pathways >> Epigenetics >> Histone Methyltransferase

EZH2 WT:0.7 nM (Ki)

EZH2 Y641N:3.0 nM (Ki)

PF-06726304 (Compound 31) inhibits H3K27me3 in Karpas-422 with an IC50 of 15 nM[1]. PF-06726304 inhibits the proliferation of Karpas-422 cells that harbor wild-type EZH2 with an IC50 of 25 nM[1].

PF-06726304 (200 and 300 mg/kg; BID for 20 days) inhibits tumor growth and induces robust modulation of downstream biomarkers in a subcutaneous Karpas-422 xenograft model[1]. Animal Model: Female Scid beige mice (6-8 weeks old) with Karpas-422 xenograft model[1] Dosage: 200 and 300 mg/kg Administration: Given BID for 20 days Result: Inhibited tumor growth and induced robust modulation of downstream biomarkers in a subcutaneous Karpas-422 xenograft model.

[1]. Kung PP, et al. Design and Synthesis of Pyridone-Containing 3,4-Dihydroisoquinoline-1(2H)-ones as a Novel Class of Enhancer of Zeste Homolog 2 (EZH2) Inhibitors. J Med Chem. 2016 Sep 22;59(18):8306-25.