SZM-610(SZM-610) - 药物靶点：RIPK1 x RIPK3_在研适应症：炎症_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

RIPK1 x RIPK3

作用机制

RIPK1抑制剂(受体相互作用的丝氨酸/苏氨酸蛋白激酶-1抑制剂)、RIPK3抑制剂(receptor interacting serine/threonine kinase 3 inhibitors)

治疗领域

其他疾病

在研适应症

炎症

非在研适应症-

原研机构

浙江工业大学

在研机构

浙江工业大学

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)临床前

特殊审评-

结构

分子式C26H19F4N3O4S

InChIKeyPZBUOCXBGCVSAF-UHFFFAOYSA-N

CAS号2304617-33-0

关联

100 项与 SZM-610 相关的临床结果

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100 项与 SZM-610 相关的转化医学

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100 项与 SZM-610 相关的专利（医药）

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1

项与 SZM-610 相关的文献（医药）

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

Insight from Linker Investigations: Discovery of a Novel Phenylbenzothiazole Necroptosis Inhibitor Targeting Receptor-Interacting Protein Kinase 1 (RIPK1) from a Phenoxybenzothiazole Compound with Dual RIPK1/3 Targeting Activity

1区 · 医学

Article

作者: Chen, Fen-Er ; Zhuang, Chunlin ; Yao, Hou-Zong ; Fang, Jing-Jie

Necroptosis, a regulated cell death form, is a critical contributor in various inflammatory diseases. We previously identified a phenoxybenzothiazole SZM-610 as a RIPK1 and RIPK3 necroptosis inhibitor. We conducted extensive studies to investigate different chemical components' effects on antinecroptosis activity and RIPK1/3 activity. This study focused on replacing the linker in phenoxybenzothiazoles to assess its impact. Remarkably, compound 10, bearing a novel 3,2'-phenylbenzothiazole scaffold, exhibited fourfold more potent nanomolar activity than SZM-610. Unlike SZM-610, this compound inhibited RIPK1 (K_d = 17 nM) and eliminated RIPK3 inhibition at 5000 nM. Various linkages confirmed the 3,2'-phenylbenzothiazole superior potency. Moreover, this compound specifically inhibited necroptosis by inhibiting RIPK1, RIPK3, and MLKL phosphorylation. In a TNF-induced inflammatory model, it dose-dependently (1.25-5 mg/kg) protected mice from hypothermia and death, surpassing SZM-610's effectiveness. These findings highlight 3,2'-phenylbenzothiazole as a promising lead structure for developing drugs targeting necroptosis-related diseases.

100 项与 SZM-610 相关的药物交易

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