Inhibitors of protein methyltransferases as chemical tools.

Abstract:

:Protein methyltransferases (PMT)s play essential roles in many biological processes through methylation of histones and diverse nonhistone substrates. Dysregulation of these enzymes has been implicated in many diseases including cancers. While PMT-associated biology can be probed via genetic perturbation, this approach targets full-length PMTs rather than their methyltransferase activities and often lacks temporal, spatial and dose controls (timing, location and amount of dosed compounds). By contrast, small-molecule inhibitors of PMTs can be designed to specifically target the methyltransferase domains in a temporal, spatial and dose-dependent manner. This utility has motivated the development of hundreds of PMT inhibitors, but meanwhile can make it challenging to select the most suitable PMT inhibitors to interrogate PMT-associated biology. This perspective aims to provide timely guidance to evaluate these PMT inhibitors in their relevant biological contexts.

journal_name

Epigenomics

journal_title

Epigenomics

authors

Luo M

doi

10.2217/epi.15.87

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

1327-38

issue

8

eissn

1750-1911

issn

1750-192X

journal_volume

7

pub_type

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