PF-06821497

PF-06821497 (compound 23a) is a potent, selective and orally active Enhancer of Zeste Homolog 2 (EZH2) inhibitor, with a Ki value <0.1 nM against mutant Y641N EZH2. Exhibits robust tumor growth inhibition[1].

Research Areas >> Cancer

Signaling Pathways >> Epigenetics >> Histone Methyltransferase

Signaling Pathways >> Epigenetics >> Epigenetic Reader Domain

Ki: <0.1 nM (Y641N EZH2)[1].

PF-06821497 (compound 23a: 100 mg/kg, PO twice daily for 31 days) treatment results in significant inhibition of tumor growth, and the the tumor regressition effect can be sustained for another 40 days after the terminal administration[1]. PF-06821497 with the dose of 300 mg/kg has minimal impact on animal body weights[1]. Animal Model: Mice bearing Karpas-422 DLBCL tumor xenografts (which contain the Y641N EZH2 mutation)[1]. Dosage: 100 mg/kg and 300 mg/kg. Administration: PO twice daily for 31 days. Result: 100 mg/kg dose resulted in significant inhibition of tumor growth and 300 mg/kg dose minimal effected animal body weights.

[1]. Kung PP, et al. Optimization of Orally Bioavailable Enhancer of Zeste Homolog 2 (EZH2) Inhibitors Using Ligand and Property-Based Design Strategies: Identification of Development Candidate (R)-5,8-Dichloro-7-(methoxy(oxetan-3-yl)methyl)-2-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3,4-dihydroisoquinolin-1(2H)-one (PF-06821497). J Med Chem. 2018 Feb 8;61(3):650-665.