YW-2065(YW-2065) - 药物靶点：AMPK x AXIN1_在研适应症：结直肠癌_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Pyrazole-4-Carboxamide

靶点

AMPK x AXIN1

作用机制

AMPK激动剂(AMP活化蛋白激酶激动剂)、AXIN1刺激剂(axin 1 stimulants)

治疗领域

肿瘤消化系统疾病

在研适应症

结直肠癌

非在研适应症-

原研机构

University of Maryland Baltimore

在研机构

University of Maryland Baltimore

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C20H15BrN4O

InChIKeyATYUYECWVYSPBS-UHFFFAOYSA-N

CAS号2131223-85-1

关联

100 项与 YW-2065 相关的临床结果

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100 项与 YW-2065 相关的转化医学

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100 项与 YW-2065 相关的专利（医药）

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1

项与 YW-2065 相关的文献（医药）

2019-12-26·Journal of Medicinal Chemistry1区 · 医学

Pyrazole-4-Carboxamide (YW2065): A Therapeutic Candidate for Colorectal Cancer via Dual Activities of Wnt/β-Catenin Signaling Inhibition and AMP-Activated Protein Kinase (AMPK) Activation

1区 · 医学

Article

作者: Xue, Fengtian ; Shu, Yan ; Sakamuru, Srilatha ; Xia, Menghang ; Guo, Dong ; Yang, Hong ; Yang, Wei ; Obianom, Obinna N. ; Ai, Yong ; Li, Yingjun

Dysregulation of the Wnt/β-catenin signaling pathway has been widely recognized as a pathogenic mechanism for colorectal cancer (CRC). Although numerous Wnt inhibitors have been developed, they commonly suffer from toxicity and unintended effects. Moreover, concerns have been raised in targeting this pathway because of its critical roles in maintaining stem cells and regenerating tissues and organs. On the basis of the anthelmintic drug pyrvinium and previous lead FX1128, we have developed a compound YW2065 (1c) which demonstrated excellent anti-CRC effects in vitro and in vivo. YW2065 achieves its inhibitory activity for Wnt signaling by stabilizing Axin-1, a scaffolding protein that regulates proteasome degradation of β-catenin. Simultaneously, YW2065 also led to the activation of the tumor suppressor AMPK, providing an additional anticancer mechanism. In addition, YW2065 showed favorable pharmacokinetic properties without obvious toxicity. The anti-CRC effect of YW2065 was highlighted by its promising efficacy in a mice xenograft model.

100 项与 YW-2065 相关的药物交易

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