Inhibitors of protein methyltransferases as chemical tools Journal Article
| Author: | Luo, M. |
| Article Title: | 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. © 2015 Future Medicine Ltd. |
| Keywords: | protein expression; unclassified drug; review; nonhuman; enzyme inhibition; protein protein interaction; in vivo study; drug potency; drug structure; in vitro study; enzyme activity; drug development; drug selectivity; cancer resistance; drug mechanism; histone h3; binding site; dimerization; drug bioavailability; conformational transition; protein methyltransferase; histone methylation; protein methyltransferase inhibitor; methyltransferase inhibitor; priority journal; ic50; chemical probe; moa; off-target effects; pkmt; prmt; target engagement; ec50 |
| Journal Title: | Epigenomics |
| Volume: | 7 |
| Issue: | 8 |
| ISSN: | 1750-1911 |
| Publisher: | Future Medicine |
| Date Published: | 2015-01-01 |
| Start Page: | 1327 |
| End Page: | 1338 |
| Language: | English |
| DOI: | 10.2217/epi.15.87 |
| PROVIDER: | scopus |
| PUBMED: | 26646500 |
| PMCID: | PMC4828241 |
| DOI/URL: | |
| Notes: | Review -- Export Date: 7 January 2016 -- 1327 -- Source: Scopus |
