Rasarfin(Rasarfin) - 药物靶点：ARF6 x RAS_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

ARF6 x RAS

作用机制

ARF6 inhibitors(ADP ribosylation factor 6 inhibitors)、RAS 抑制剂(RAS type GTPase family inhibitors)

治疗领域

肿瘤

在研适应症

肿瘤

非在研适应症-

原研机构

McGill University

在研机构

McGill University

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 Rasarfin 相关的临床结果

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100 项与 Rasarfin 相关的转化医学

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100 项与 Rasarfin 相关的专利（医药）

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1

项与 Rasarfin 相关的文献（医药）

Nature Communications1区 · 综合性期刊

Discovery of a dual Ras and ARF6 inhibitor from a GPCR endocytosis screen

1区 · 综合性期刊

ArticleOA

作者: Armando, Sylvain ; Selent, Jana ; Lamarche-Vane, Nathalie ; Bouvier, Michel ; Lara-Márquez, Mónica ; Campbell, Shirley ; Radresa, Olivier ; Schuetz, Doris A ; Stepniewski, Tomasz M ; Laporte, Stéphane A ; Giubilaro, Jenna ; Claing, Audrey ; Namkung, Yoon ; Duchaine, Jean ; Khoury, Etienne ; Marinier, Anne ; Beautrait, Alexandre

AbstractInternalization and intracellular trafficking of G protein-coupled receptors (GPCRs) play pivotal roles in cell responsiveness. Dysregulation in receptor trafficking can lead to aberrant signaling and cell behavior. Here, using an endosomal BRET-based assay in a high-throughput screen with the prototypical GPCR angiotensin II type 1 receptor (AT1R), we sought to identify receptor trafficking inhibitors from a library of ~115,000 small molecules. We identified a novel dual Ras and ARF6 inhibitor, which we named Rasarfin, that blocks agonist-mediated internalization of AT1R and other GPCRs. Rasarfin also potently inhibits agonist-induced ERK1/2 signaling by GPCRs, and MAPK and Akt signaling by EGFR, as well as prevents cancer cell proliferation. In silico modeling and in vitro studies reveal a unique binding modality of Rasarfin within the SOS-binding domain of Ras. Our findings unveil a class of dual small G protein inhibitors for receptor trafficking and signaling, useful for the inhibition of oncogenic cellular responses.

100 项与 Rasarfin 相关的药物交易

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