SW-101(SW-101) - 药物靶点：HDAC6_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

HDAC6

作用机制

HDAC6抑制剂(组蛋白去乙酰化酶-6抑制剂)

治疗领域

神经系统疾病遗传病与畸形其他疾病

在研适应症-

非在研适应症

腓骨肌萎缩症

原研机构

Bright Minds Biosciences, Inc.

在研机构-

非在研机构

Bright Minds Biosciences, Inc.

最高研发阶段终止临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

关联

100 项与 SW-101 相关的临床结果

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100 项与 SW-101 相关的转化医学

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100 项与 SW-101 相关的专利（医药）

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1

项与 SW-101 相关的文献（医药）

2021-04-22·Journal of Medicinal Chemistry1区 · 医学

Tetrahydroquinoline-Capped Histone Deacetylase 6 Inhibitor SW-101 Ameliorates Pathological Phenotypes in a Charcot–Marie–Tooth Type 2A Mouse Model

1区 · 医学

Article

作者: Picci, Cristina ; Van Den Bosch, Ludo ; Benoy, Veronick ; Zhang, Guiping ; Kutil, Zsófia ; Bařinka, Cyril ; Shen, Sida ; Zimprich, Chad A. ; Langley, Brett ; Pavlíček, Jiří ; Kozikowski, Alan P. ; Tavares, Maurício T. ; Ustinova, Kseniya ; Robers, Matthew B.

Histone deacetylase 6 (HDAC6) is a promising therapeutic target for the treatment of neurodegenerative disorders. SW-100 (1a), a phenylhydroxamate-based HDAC6 inhibitor (HDAC6i) bearing a tetrahydroquinoline (THQ) capping group, is a highly potent and selective HDAC6i that was shown to be effective in mouse models of Fragile X syndrome and Charcot-Marie-Tooth disease type 2A (CMT2A). In this study, we report the discovery of a new THQ-capped HDAC6i, termed SW-101 (1s), that possesses excellent HDAC6 potency and selectivity, together with markedly improved metabolic stability and druglike properties compared to SW-100 (1a). X-ray crystallography data reveal the molecular basis of HDAC6 inhibition by SW-101 (1s). Importantly, we demonstrate that SW-101 (1s) treatment elevates the impaired level of acetylated α-tubulin in the distal sciatic nerve, counteracts progressive motor dysfunction, and ameliorates neuropathic symptoms in a CMT2A mouse model bearing mutant MFN2. Taken together, these results bode well for the further development of SW-101 (1s) as a disease-modifying HDAC6i.

100 项与 SW-101 相关的药物交易

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