Kyushu Institute of Technology

Riken Corporation

Sumitomo Pharmaceuticals Company Limited

Japan Energy Corporation

Norikazu Nishino

Minoru Yoshida

Sueharu Horinouchi

Yasuhiko Komatsu

Tsutomu Mimoto

Akihiro Ito

Junichi Nakagawa

Yasushi Takemoto

Provided are a method for measuring histone methyltransferase activity, a method for screening for compounds that inhibit histone methyltransferase activity, a reagent kit for measuring histone methyltransferase activity, and a kit for screening for compounds that inhibit histone methyltransferase activity. A substrate compound represented by general formula (I): R-X-K-R(I), or a salt thereof, wherein Rrepresents a hydrogen atom or a protecting group for an amino terminus; X represents a peptide consisting of 0 or 1 or more amino acid residues; K represents a lysine residue; and Rrepresents a dye label linked via an amide bond to the carbonyl terminus of a lysine residue, wherein the cleavage of the amide bond by peptidase changes the fluorescence property or chromogenic property of the dye label, and the methylation of the &#x3b5; amino group of the lysine residue by the histone methyltransferase decreases susceptibility to peptidase, is used.

Method for assaying histone methylation enzyme activity

A novel compound having histone deacetylase-inhibiting activity which is a cyclic tetrapeptide derivative represented by the general formula (1) given below and a pharmaceutical composition comprising such compound as an active ingredient. (In the formula, the cyclic tetrapeptide moiety has a known structure; Rand Reach independently represents an alkylene group containing 1 to 6 carbon atoms, which may be branched; X represents a group or bond selected from among &#x2014;CO&#x2014;, &#x2014;O&#x2014;, &#x2014;S&#x2014; or &#x2014;SO&#x2014;; Y represents a hydrogen or halogen atom, a phenyl group (including a substituted form), a pyridyl group (including a substituted form), an alkyl group (including a halogen-substituted form; hereinafter the same shall apply) containing 1 to 6 carbon atoms, an alkyloxy group containing 1 to 6 carbon atoms, an alkylcarbonyl group containing 1 to 6 carbon atoms, an alkyloxycarbonyl group containing 1 to 6 carbon atoms, an alkylthio group containing 1 to 6 carbon atoms, an alkylthiocarbonyl group containing 1 to 6 carbon atoms or a mono- or dialkylamino group containing 1 to 6 carbon atoms; when Y is a phenyl group (including a substituted form) or a pyridyl group (including a substituted form), it may form a further cyclic structure bound to R.) 

Compound having histone deacetylase-inhibiting activity, and pharmaceutical composition comprising the compound as an active ingredient

HDAC inhibitor of the general formula (1) exhibits strong inhibitory activity against various subtype HDACs. The compound is useful as a medicinal agent for the treatment or prevention of HDAC 1, 4 and 6-related diseases. There is further provided a process for producing the compound which is capable of readily synthesizing various types of compounds and is promising in the contribution to the development of HDAC inhibitor having novel properties, etc.

Histone deacetylase inhibitor and process for producing the same

Compounds represented by formula (1) have strong inhibitory activity that is selective towards HDAC1 and HDAC4. Therefore, the compounds of the present invention are useful as pharmaceutical agents for treating or preventing diseases caused by HDAC1 and HDAC4. 

Histone deacetylase inhibitors and methods for producing the same

Cyclic tetrapeptide derivatives and pharmaceutical uses thereof

Cyclic tetrapeptide derivatives and medicinal use thereof

Growing community of inventors

Fukuoka, Japan

Norikazu Nishino