GB-1874(GB-1874) - 药物靶点：CTNNB1_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

靶点

CTNNB1

作用机制

CTNNB1抑制剂(连环素β1抑制剂)

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

National Cancer Centre of Singapore Pte Ltd.

在研机构

National Cancer Centre of Singapore Pte Ltd.

Agency for Science, Technology & Research

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 GB-1874 相关的临床结果

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100 项与 GB-1874 相关的转化医学

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100 项与 GB-1874 相关的专利（医药）

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1

项与 GB-1874 相关的文献（医药）

2021-06-01·iScience2区 · 综合性期刊

Molecular docking-aided identification of small molecule inhibitors targeting β-catenin-TCF4 interaction

2区 · 综合性期刊

ArticleOA

作者: Du, Weina ; Zhang, Xiaoqian ; Fan, Hao ; Oguz, Gokce ; Tan, Iain Bee Huat ; Masirevic, Srdan ; DasGupta, Ramanuj ; Gocha, Tenzin ; Low, Joo-Leng ; Yim, Daniel Guo Rong ; Chen, Ming Wei ; Ramasamy, Adaikalavan

Here we report a molecular docking-based approach to identify small molecules that can target the β-catenin (β-cat)-TCF4 protein-protein interaction (PPI), a key effector complex for nuclear Wnt signaling activity. Specifically, we developed and optimized a computational model of β-cat using publicly available β-cat protein crystal structures, and existing β-cat-TCF4 interaction inhibitors as the training set. Using our computational model to an in silico screen predicted 27 compounds as good binders to β-cat, of which 3 were identified to be effective against a Wnt-responsive luciferase reporter. In vitro functional validation experiments revealed GB1874 as an inhibitor of the Wnt pathway that targets the β-cat-TCF4 PPI. GB1874 also affected the proliferation and stemness of Wnt-addicted colorectal cancer (CRC) cells in vitro. Encouragingly, GB1874 inhibited the growth of CRC tumor xenografts in vivo, thus demonstrating its potential for further development into therapeutics against Wnt-associated cancer indications.

100 项与 GB-1874 相关的药物交易

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