Compound 12a(Taisho Pharmaceutical )(Compound 12a(Taisho Pharmaceutical )) - 药物靶点：HPSE_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

HPSE

作用机制

HPSE modulators(Heparanase modulators)

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

Taisho Pharmaceutical Co., Ltd.

在研机构

Centro de Estudios en Alimentos Procesados

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 Compound 12a(Taisho Pharmaceutical ) 相关的临床结果

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100 项与 Compound 12a(Taisho Pharmaceutical ) 相关的转化医学

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100 项与 Compound 12a(Taisho Pharmaceutical ) 相关的专利（医药）

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1

项与 Compound 12a(Taisho Pharmaceutical ) 相关的文献（医药）

2024-11-14·Journal of Medicinal Chemistry

Structural Modification and Pharmacological Evaluation of (Thiadiazol-2-yl)pyrazines as Novel Piezo1 Agonists for the Intervention of Disuse Osteoporosis

Article

作者: Ma, Ding ; Yao, Yujia ; Zhang, Ao ; Ding, Chunyong ; Hao, Ruihan ; Tang, Hairong ; Zhang, Xiaoling

Piezo1 plays a pivotal role in regulating bone remodeling and homeostasis and has emerged as a promising target for chemical intervention in disuse osteoporosis. Nevertheless, the development of small-molecule Piezo1 agonists is still in its infancy, and highly efficacious Piezo1 agonists are urgently required. In this study, by shedding light on the structural novelty of the canonical Piezo1 agonist Yoda1, we initiated a structural optimization campaign based on the (thiadiazol-2-yl)pyrazine scaffold. A deuterated compound 12a was identified to be the most potent candidate against Piezo1 with an EC₅₀ value of 2.21 μM, which was over 20-fold more potent than the reference Yoda1. This compound effectively activated Piezo1 and initiated Ca²⁺ influx in MSCs and promoted MSC osteogenesis via activating the Ca²⁺-related Erk signaling pathway. Furthermore, compound 12a was found to alleviate disuse osteoporosis with a desirable safety profile in a HU (hindlimb-unloading) rat model, thus warranting it as a potential probe for further investigation.

100 项与 Compound 12a(Taisho Pharmaceutical ) 相关的药物交易

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