PTPN1/2 inhibition(Nerio)(PTPN1/2 inhibition(Nerio)) - 药物靶点：PTP1B x PTPN2_在研适应症：肿瘤_专利_临床

概要

基本信息

药物类型

小分子化药

别名-

靶点

PTP1B x PTPN2

作用机制

PTP1B抑制剂(蛋白酪氨酸磷酸酶-1B抑制剂)、PTPN2 抑制剂(蛋白酪氨酸磷酸酶非受体2型抑制剂)

治疗领域

肿瘤

在研适应症

肿瘤

非在研适应症-

原研机构

Boehringer Ingelheim GmbH

Nerio Therapeutics, Inc.初创企业

在研机构

Boehringer Ingelheim GmbH

Nerio Therapeutics, Inc.初创企业

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 PTPN1/2 inhibition(Nerio) 相关的临床结果

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100 项与 PTPN1/2 inhibition(Nerio) 相关的转化医学

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100 项与 PTPN1/2 inhibition(Nerio) 相关的专利（医药）

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1

项与 PTPN1/2 inhibition(Nerio) 相关的文献（医药）

2025-01-01·Life Science Alliance

PTPN1/2 inhibition promotes muscle stem cell differentiation in Duchenne muscular dystrophy

Article

作者: Liu, Yiyang ; Aubry, Isabelle ; Robertson, Rebecca ; Filippelli, Romina L ; Tremblay, Michel L ; Chang, Natasha C ; Granet, Jules A ; Li, Shulei

Duchenne muscular dystrophy (DMD) is a lethal disease caused by mutations in theDMDgene that encodes dystrophin. Dystrophin deficiency also impacts muscle stem cells (MuSCs), resulting in impaired asymmetric stem cell division and myogenic commitment. Using MuSCs from DMD patients and the DMD mouse modelmdx, we found that PTPN1 phosphatase expression is up-regulated and STAT3 phosphorylation is concomitantly down-regulated in DMD MuSCs. To restore STAT3-mediated myogenic signaling, we examined the effect of K884, a novel PTPN1/2 inhibitor, on DMD MuSCs. Treatment with K884 enhanced STAT3 phosphorylation and promoted myogenic differentiation of DMD patient-derived MuSCs. In MuSCs frommdxmice, K884 treatment increased the number of asymmetric cell divisions, correlating with enhanced myogenic differentiation. Interestingly, the pro-myogenic effect of K884 is specific to human and murine DMD MuSCs and is absent from control MuSCs. Moreover, PTPN1/2 loss-of-function experiments indicate that the pro-myogenic impact of K884 is mediated mainly through PTPN1. We propose that PTPN1/2 inhibition may serve as a therapeutic strategy to restore the myogenic function of MuSCs in DMD.

100 项与 PTPN1/2 inhibition(Nerio) 相关的药物交易

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