Nucleoside protein arginine methyltransferase 5 (PRMT5) inhibitors

Hong Lin; Juan I Luengo

doi:10.1016/j.bmcl.2019.03.042

Nucleoside protein arginine methyltransferase 5 (PRMT5) inhibitors

Bioorg Med Chem Lett. 2019 Jun 1;29(11):1264-1269. doi: 10.1016/j.bmcl.2019.03.042. Epub 2019 Mar 27.

Authors

Hong Lin¹, Juan I Luengo¹

Affiliation

¹ Prelude Therapeutics, 200 Powder Mill Road, Wilmington, DE 19803, United States.

PMID: 30956011
DOI: 10.1016/j.bmcl.2019.03.042

Abstract

Protein Arginine Methyltransferase 5 (PRMT5) is known to symmetrically dimethylate numerous cytosolic and nuclear proteins that are involved in a variety of cellular processes. Recent findings have revealed its potential as a cancer therapeutic target. PRMT5 selective inhibitors, GSK3326595, a substrate competitive inhibitor, and JNJ64619178, a SAM (S-adenosyl-l-methionine) mimetic/competitive inhibitor, have entered clinic trials for multiple cancer types. This review focuses on the recent developments in SAM mimetic nucleoside PRMT5 inhibitors, their SAR and structural insight based on published co-crystal structures.

Keywords: Nucleoside; PRMT5; SAR.

Publication types

Review

MeSH terms

Dose-Response Relationship, Drug
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Molecular Structure
Protein-Arginine N-Methyltransferases / antagonists & inhibitors*
Protein-Arginine N-Methyltransferases / metabolism
Structure-Activity Relationship

Substances

Enzyme Inhibitors
PRMT5 protein, human
Protein-Arginine N-Methyltransferases