Format

Send to

Choose Destination
J Med Chem. 2012 Nov 26;55(22):9875-90. doi: 10.1021/jm301097p. Epub 2012 Nov 2.

Identification of small-molecule enhancers of arginine methylation catalyzed by coactivator-associated arginine methyltransferase 1.

Author information

1
Dipartimento di Scienze Farmaceutiche e Biomediche, Epigenetic Med Chem Lab, Università degli Studi di Salerno, Via Ponte Don Melillo, I-84084 Fisciano (SA), Italy.

Abstract

Arginine methylation is a common post-translational modification that is crucial in modulating gene expression at multiple critical levels. The arginine methyltransferases (PRMTs) are envisaged as promising druggable targets, but their role in physiological and pathological pathways is far from being clear due to the limited number of modulators reported to date. In this effort, enzyme activators can be invaluable tools useful as gain-of-function reagents to interrogate the biological roles in cells and in vivo of PRMTs. Yet the identification of such molecules is rarely pursued. Herein we describe a series of aryl ureido acetamido indole carboxylates (dubbed "uracandolates"), able to increase the methylation of histone (H3) or nonhistone (polyadenylate-binding protein 1, PABP1) substrates induced by coactivator-associated arginine methyltransferase 1 (CARM1), both in in vitro and cellular settings. To the best of our knowledge, this is the first report of compounds acting as CARM1 activators.

PMID:
23095008
PMCID:
PMC3508294
DOI:
10.1021/jm301097p
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for American Chemical Society Icon for PubMed Central
Loading ...
Support Center