TRIM7 Inhibitor(Shattuck Labs)(TRIM7 Inhibitor(Shattuck Labs)) - 药物靶点：TRIM7_在研适应症：肿瘤_专利_临床

概要

基本信息

药物类型

化学药

别名

TRIM7抑制剂(Shattuck Labs)

靶点

TRIM7

作用机制

TRIM7 inhibitors(tripartite motif containing 7 inhibitors)

治疗领域

肿瘤

在研适应症

肿瘤

非在研适应症-

原研机构

Shattuck Labs, Inc.

R2M Pharma, Inc.初创企业

在研机构

R2M Pharma, Inc.初创企业

Shattuck Labs, Inc.

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-

关联

100 项与 TRIM7 Inhibitor(Shattuck Labs) 相关的临床结果

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100 项与 TRIM7 Inhibitor(Shattuck Labs) 相关的转化医学

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100 项与 TRIM7 Inhibitor(Shattuck Labs) 相关的专利（医药）

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1

项与 TRIM7 Inhibitor(Shattuck Labs) 相关的文献（医药）

2024-12-31·Journal of Enzyme Inhibition and Medicinal Chemistry

Synthesis and biological evaluation of ortho -phenyl phenylhydroxamic acids containing phenothiazine with improved selectivity for class IIa histone deacetylases

Article

作者: Hsu, Kai-Cheng ; Huang, Wei-Jan ; Chu, Jung-Chun ; Huang, Yu-Wen ; Hu, Jing-Lan ; Weng, Jing-Ru ; Lin, Tony Eight ; Yen, Shih-Chung ; Huang, Yun-Yi

Class IIa histone deacetylases (HDACs) have been linked to tumorigenesis in various cancers. Previously, we designed phenylhydroxamic acid LH4f as a potent class IIa HDAC inhibitor. However, it also unselectively inhibited class I and class IIb HDACs. To enhance the compound's selectivity towards class IIa HDACs, the ortho-phenyl group from the selective HDAC7 inhibitor 1 is incorporated into ortho position of the phenylhydroxamic acid in LH4f. Compared to LH4f, most resulting compounds displayed substantially improved selectivity towards the class IIa HDACs. Notably, compound 7 g exhibited the strongest HDAC9 inhibition with an IC₅₀ value of 40 nM. Molecular modelling further identified the key interactions of compound 7 g bound to HDAC9. Compound 7 g significantly inhibited several human cancer cells, induced apoptosis, modulated caspase-related proteins as well as p38, and caused DNA damage. These findings suggest the potential of class IIa HDAC inhibitors as lead compounds for the development of cancer therapeutics.

100 项与 TRIM7 Inhibitor(Shattuck Labs) 相关的药物交易

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