Design, Synthesis, and Pharmacological Evaluation of Second Generation EZH2 Inhibitors with Long Residence Time

• Published in: ACS medicinal chemistry letters Vol. 11; no. 6; pp. 1205 - 1212
• Main Authors: Khanna, Avinash, Cote, Alexandre, Arora, Shilpi, Moine, Ludivine, Gehling, Victor S., Brenneman, Jehrod, Cantone, Nico, Stuckey, Jacob, Apte, Shruti, Ramakrishnan, Ashwin, Bruderek, Kamil, Bradley, William D., Audia, James E., Cummings, Richard T., Sims, Robert J., Trojer, Patrick, Levell, Julian R.
• Format: Journal Article
• Language: English
• Published: WASHINGTON Amer Chemical Soc 11.06.2020; American Chemical Society
• Subjects: Chemistry, Medicinal; Letter; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Science & Technology; POTENT; Residence time; PRC2; COMPLEXES; thiomethyl pyridone; MUTATIONS; IDENTIFICATION; CELL; CYP induction; EZH2

Histone methyltransferase EZH2, which is the catalytic subunit of the PRC2 complex, catalyzes the methylation of histone H3K27-a transcriptionally repressive post-translational modification (PTM). EZH2 is commonly mutated in hematologic malignancies and frequently overexpressed in solid tumors, wher...