SH-491(SH-491) - 药物靶点：CTSK x MMP9 x TRAP1_在研适应症：骨质疏松症_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

CTSK x MMP9 x TRAP1

作用机制

CTSK抑制剂(组织蛋白酶K抑制剂)、MMP9基因抑制剂、TRAP1拮抗剂(TNF receptor associated protein 1 antagonists)

治疗领域

内分泌与代谢疾病皮肤和肌肉骨骼疾病

在研适应症

骨质疏松症

非在研适应症-

原研机构

华东师范大学

在研机构

华东师范大学

非在研机构-

最高研发阶段药物发现

首次获批日期-

最高研发阶段(中国)药物发现

特殊审评-

结构

分子式C33H50N2O

InChIKeySDNYORIEEOHMNL-WZNPBPMFSA-N

CAS号-

关联

100 项与 SH-491 相关的临床结果

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100 项与 SH-491 相关的转化医学

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100 项与 SH-491 相关的专利（医药）

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1

项与 SH-491 相关的文献（医药）

2023-09-14·Journal of medicinal chemistry1区 · 医学

Synthesis and Biological Evaluation of Heterocyclic Ring-Fused 20(S)-Protopanaxadiol Derivatives as Potent Antiosteoporosis Agents.

1区 · 医学

Article

作者: Qiu, Wen-Wei ; Zhang, Jiahui ; Ning, Ruo-Nan ; Li, Chen-Chen ; Xu, Xing ; Zhang, Jing-Zan ; Jiang, Min ; Wang, Shuan-Jing

A series of heterocyclic ring-fused derivatives of 20(S)-protopanaxadiol (PPD) were synthesized and evaluated for their inhibitory effects on RANKL-induced osteoclastogenesis. Among these compounds, 33 (SH491, IC₅₀ = 11.8 nM) showed the highest potency with 100% inhibition at 0.1 μM and 44.4% inhibition at an even lower concentration of 0.01 μM, which was much more potent than the lead compound PPD (IC₅₀ = 10.3 μM). Cytotoxicity tests indicated that the inhibitory effect of these compounds on RANKL-induced osteoclast differentiation was not due to their cytotoxicity. Interestingly, SH491 also exhibited a notable impact on the osteoblastogenesis of MC3T3-E1 preosteoblasts. Mechanistic studies revealed that SH491 inhibits the expression of osteoclastogenesis-related marker genes and proteins, including TRAP, CTSK, MMP-9, and ATPase v0d2. In vivo, SH491 could dramatically decrease the ovariectomy-induced osteoclast activity and relieve osteoporosis obviously. Thus, these PPD derivatives could be served as promising leads for the development of novel antiosteoporosis agents.

100 项与 SH-491 相关的药物交易

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