KPZ-560(KPZ-560) - 药物靶点：HDAC1 x HDAC2_在研适应症：乳腺癌_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

HDAC1 x HDAC2

作用机制

HDAC1抑制剂(组蛋白去乙酰化酶-1抑制剂)、HDAC2抑制剂(组蛋白去乙酰化酶-2抑制剂)

治疗领域

肿瘤皮肤和肌肉骨骼疾病

在研适应症

乳腺癌

非在研适应症-

原研机构

Kyoto Prefectural University of Medicine

在研机构

Kyoto Prefectural University of Medicine

非在研机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C26H21N5O3S2

InChIKeyCKPHTEVIQGSUMQ-UHFFFAOYSA-N

CAS号2397562-43-3

关联

100 项与 KPZ-560 相关的临床结果

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100 项与 KPZ-560 相关的转化医学

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100 项与 KPZ-560 相关的专利（医药）

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1

项与 KPZ-560 相关的文献（医药）

2023-11-23·Journal of Medicinal Chemistry1区 · 医学

Discovery of Selective Histone Deacetylase 1 and 2 Inhibitors: Screening of a Focused Library Constructed by Click Chemistry, Kinetic Binding Analysis, and Biological Evaluation

1区 · 医学

Article

作者: Tojo, Toshifumi ; Li, Ying ; Ito, Shinji ; Jaikhan, Pattaporn ; Hui, Zi ; Uchida, Shusaku ; Takada, Yuri ; Suzuki, Miki ; Sakai, Toshiyuki ; Masuda, Mitsuharu ; Sowa, Yoshihiro ; Ota, Yosuke ; Oba, Makoto ; Yamashita, Yasunobu ; 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 项与 KPZ-560 相关的药物交易

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