Synthesis and activity of N-oxalylglycine and its derivatives as Jumonji C-domain-containing histone lysine demethylase inhibitors

Shohei Hamada; Tae-Dong Kim; Takayoshi Suzuki; Yukihiro Itoh; Hiroki Tsumoto; Hidehiko Nakagawa; Ralf Janknecht; Naoki Miyata

doi:10.1016/j.bmcl.2009.03.098

Synthesis and activity of N-oxalylglycine and its derivatives as Jumonji C-domain-containing histone lysine demethylase inhibitors

Bioorg Med Chem Lett. 2009 May 15;19(10):2852-5. doi: 10.1016/j.bmcl.2009.03.098. Epub 2009 Mar 26.

Authors

Shohei Hamada¹, Tae-Dong Kim, Takayoshi Suzuki, Yukihiro Itoh, Hiroki Tsumoto, Hidehiko Nakagawa, Ralf Janknecht, Naoki Miyata

Affiliation

¹ Nagoya City University, Tanabe-dori, Mizuho-ku, Aichi, Japan.

PMID: 19359167
DOI: 10.1016/j.bmcl.2009.03.098

Abstract

N-Oxalylglycine (NOG) derivatives were synthesized, and their inhibitory effect on histone lysine demethylase activity was evaluated. NOG and compound 1 inhibited histone lysine demethylases JMJD2A, 2C and 2D in enzyme assays, and their dimethyl ester prodrugs DMOG and 21 exerted histone lysine methylating activity in cellular assays.

Publication types

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

MeSH terms

Amino Acids, Dicarboxylic / chemical synthesis
Amino Acids, Dicarboxylic / chemistry*
Amino Acids, Dicarboxylic / pharmacology
Cell Line
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology
Humans
Jumonji Domain-Containing Histone Demethylases
Neoplasm Proteins / antagonists & inhibitors*
Neoplasm Proteins / metabolism
Oxidoreductases, N-Demethylating / antagonists & inhibitors*
Oxidoreductases, N-Demethylating / metabolism
Transcription Factors / antagonists & inhibitors*
Transcription Factors / metabolism

Substances

Amino Acids, Dicarboxylic
Enzyme Inhibitors
KDM4C protein, human
Neoplasm Proteins
Transcription Factors
Jumonji Domain-Containing Histone Demethylases
KDM4D protein, human
KDM4A protein, human
Oxidoreductases, N-Demethylating
oxalylglycine