CNX-2006(CNX-2006) - 药物靶点：EGFR_在研适应症：EGFR突变肺癌_专利_临床

概要

基本信息

药物类型

小分子化药

别名-

靶点

EGFR

作用机制

EGFR拮抗剂(表皮生长因子受体erbB1拮抗剂)

治疗领域

肿瘤呼吸系统疾病

在研适应症

EGFR突变肺癌

非在研适应症-

原研机构

Celgene Corp.

在研机构

Vanderbilt University

Clovis Oncology, Inc.Celgene Avilomics Research, Inc.

非在研机构-

最高研发阶段临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C26H27F4N7O2

InChIKeyBFSRTTWIPACGMI-UHFFFAOYSA-N

CAS号1375465-09-0

关联

100 项与 CNX-2006 相关的临床结果

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100 项与 CNX-2006 相关的转化医学

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100 项与 CNX-2006 相关的专利（医药）

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1

项与 CNX-2006 相关的文献（医药）

2015-12-15·Oncotarget

NF-κB drives acquired resistance to a novel mutant-selective EGFR inhibitor

Article

作者: Smit, Egbert F. ; Giovannetti, Elisa ; Galvani, Elena ; Alfieri, Roberta R. ; Peters, Godefridus J. ; Bernards, René ; Heynen, Guus J. ; Pao, William ; Sciarrillo, Rocco ; Narayan, Ravi S. ; Lee, Kwangho ; Ohashi, Kadoaki ; Leon, Leticia G. ; Sun, Jing ; Tjin Tham Sjin, Robert ; Heideman, Daniëlle A.M.

The clinical efficacy of EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) harbouring activating EGFR mutations is limited by the emergence of acquired resistance, mostly ascribed to the secondary EGFR-T790M mutation. Selective EGFR-T790M inhibitors have been proposed as a new, extremely relevant therapeutic approach. Here, we demonstrate that the novel irreversible EGFR-TKI CNX-2006, a structural analog of CO-1686, currently tested in a phase-1/2 trial, is active against in vitro and in vivo NSCLC models expressing mutant EGFR, with minimal effect on the wild-type receptor. By integration of genetic and functional analyses in isogenic cell pairs we provide evidence of the crucial role played by NF-κB1 in driving CNX-2006 acquired resistance and show that NF-κB activation may replace the oncogenic EGFR signaling in NSCLC when effective and persistent inhibition of the target is achieved in the presence of the T790M mutation. In this context, we demonstrate that the sole, either genetic or pharmacologic, inhibition of NF-κB is sufficient to reduce the viability of cells that adapted to EGFR-TKIs. Overall, our findings support the rational inhibition of members of the NF-κB pathway as a promising therapeutic option for patients who progress after treatment with novel mutant-selective EGFR-TKIs.

100 项与 CNX-2006 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
EGFR突变肺癌	临床1期	美国	Clovis Oncology, Inc.	2013-04-15
EGFR突变肺癌	临床1期	英国	Celgene Avilomics Research, Inc.	2013-04-15
EGFR突变肺癌	临床1期	美国	Vanderbilt University	2013-04-15