Delving into the Latest Updates on KPZ-560 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

HDAC1 x HDAC2

Mechanism

HDAC1 inhibitors(Histone deacetylase 1 inhibitors), HDAC2 inhibitors(Histone deacetylase 2 inhibitors)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal Diseases

Active Indication

Breast Cancer

Inactive Indication-

Originator Organization

Kyoto Prefectural University of Medicine

Active Organization

Kyoto Prefectural University of Medicine

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC26H21N5O3S2

InChIKeyCKPHTEVIQGSUMQ-UHFFFAOYSA-N

CAS Registry2397562-43-3

Author: Tojo, Toshifumi ; Li, Ying ; Ito, Shinji ; Jaikhan, Pattaporn ; Hui, Zi ; Uchida, Shusaku ; Takada, Yuri ; Suzuki, Miki ; Sakai, Toshiyuki ; Masuda, Mitsuharu ; Sowa, Yoshihiro ; Ota, Yosuke ; Yamashita, Yasunobu ; Oba, Makoto ; Itoh, Yukihiro ; Zhan, Peng ; Moriyama, Yukiko ; Suzuki, Takayoshi

Histone deacetylase 1 and 2 (HDAC1/2) inhibitors are potentially useful as tools for probing the biological functions of the isoforms and as therapeutic agents for cancer and neurodegenerative disorders. To discover potent and selective inhibitors, we screened a focused library synthesized by using click chemistry and obtained KPZ560 as an HDAC1/2-selective inhibitor. Kinetic binding analysis revealed that KPZ560 inhibits HDAC2 through a two-step slow-binding mechanism. In cellular assays, KPZ560 induced a dose- and time-dependent increase of histone acetylation and showed potent breast cancer cell growth-inhibitory activity. In addition, gene expression analyses suggested that the two-step slow-binding inhibition by KPZ560 regulated the expression of genes associated with cell proliferation and DNA damage. KPZ560 also induced neurite outgrowth of Neuro-2a cells and an increase in the spine density of granule neuron dendrites of mice. The unique two-step slow-binding character of o-aminoanilides such as KPZ560 makes them interesting candidates as therapeutic agents.

100 Deals associated with KPZ-560

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