Development of novel bisubstrate-type inhibitors of histone methyltransferase SET7/9

Shuichi Mori; Kenta Iwase; Naoko Iwanami; Yujiro Tanaka; Hiroyuki Kagechika; Tomoya Hirano

doi:10.1016/j.bmc.2010.10.022

Development of novel bisubstrate-type inhibitors of histone methyltransferase SET7/9

Bioorg Med Chem. 2010 Dec 1;18(23):8158-66. doi: 10.1016/j.bmc.2010.10.022. Epub 2010 Oct 14.

Authors

Shuichi Mori¹, Kenta Iwase, Naoko Iwanami, Yujiro Tanaka, Hiroyuki Kagechika, Tomoya Hirano

Affiliation

¹ Tokyo Medical and Dental University, Chiyoda-ku, Japan.

PMID: 21036620
DOI: 10.1016/j.bmc.2010.10.022

Abstract

Histone modification, for example, by histone deacetylase (HDAC) and histone lysine methyltransferase (HMT), plays an important role in regulating gene expression. To obtain novel inhibitors as tools for investigating the physiological function of members of the HMT family, we designed and synthesized novel inhibitors, which are amine analogues of adenosylmethionine (AdoMet; the cofactor utilized in the methylation reaction) bearing various alkylamino groups coupled via an ethylene linker. The inhibitory activities of these compounds towards SET7/9, an HMT, were evaluated. It was found that introduction of an alkylamino group increased the inhibitory activity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology
Histone-Lysine N-Methyltransferase / antagonists & inhibitors*
Histone-Lysine N-Methyltransferase / metabolism
S-Adenosylmethionine / chemical synthesis
S-Adenosylmethionine / chemistry*
S-Adenosylmethionine / pharmacology
Substrate Specificity

Substances

Enzyme Inhibitors
S-Adenosylmethionine
Histone-Lysine N-Methyltransferase
SETD7 protein, human