JSD-26(JSD-26) - 药物靶点：AKR1A1_在研适应症：急性肾损伤_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

AKR1A1

作用机制

AKR1A1抑制剂(aldo-keto reductase family 1 member A1 inhibitors)

治疗领域

泌尿生殖系统疾病

在研适应症

急性肾损伤

非在研适应症-

原研机构

Case Western Reserve University School of Medicine

在研机构

Case Western Reserve University School of Medicine

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-

结构

分子式C18H14N2O2

InChIKeyYNIGFZOTWOVBHD-GOSISDBHSA-N

CAS号2413392-38-6

关联

100 项与 JSD-26 相关的临床结果

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100 项与 JSD-26 相关的转化医学

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100 项与 JSD-26 相关的专利（医药）

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1

项与 JSD-26 相关的文献（医药）

2023-04-27·Journal of medicinal chemistry1区 · 医学

Identification of a Selective SCoR2 Inhibitor That Protects Against Acute Kidney Injury.

1区 · 医学

Article

作者: van den Akker, Focco ; Greenlee, William J ; Zhang, Rongli ; Anand, Puneet ; Hausladen, Alfred ; Rajavel, Malligarjunan ; Premont, Richard T ; Stomberski, Colin T ; Zhou, Hua-Lin ; Stamler, Jonathan S

Acute kidney injury (AKI) is associated with high morbidity and mortality, and no drugs are available clinically. Metabolic reprogramming resulting from the deletion of S-nitroso-coenzyme A reductase 2 (SCoR2; AKR1A1) protects mice against AKI, identifying SCoR2 as a potential drug target. Of the few known inhibitors of SCoR2, none are selective versus the related oxidoreductase AKR1B1, limiting therapeutic utility. To identify SCoR2 (AKR1A1) inhibitors with selectivity versus AKR1B1, analogs of the nonselective (dual 1A1/1B1) inhibitor imirestat were designed, synthesized, and evaluated. Among 57 compounds, JSD26 has 10-fold selectivity for SCoR2 versus AKR1B1 and inhibits SCoR2 potently through an uncompetitive mechanism. When dosed orally to mice, JSD26 inhibited SNO-CoA metabolic activity in multiple organs. Notably, intraperitoneal injection of JSD26 in mice protected against AKI through S-nitrosylation of pyruvate kinase M2 (PKM2), whereas imirestat was not protective. Thus, selective inhibition of SCoR2 has therapeutic potential to treat acute kidney injury.

100 项与 JSD-26 相关的药物交易

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