NCT-547(NCT-547) - 药物靶点：HSP90_在研适应症：三阴性乳腺癌_专利_临床

概要

基本信息

药物类型

化学药

别名

靶点

HSP90

作用机制

HSP90 抑制剂(Heat shock 90kDa proteins inhibitors)

治疗领域

肿瘤皮肤和肌肉骨骼疾病

在研适应症

三阴性乳腺癌

非在研适应症-

原研机构

Korea University Guro Hospital

在研机构

Korea University Guro Hospital

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C35H43N3O6

InChIKeyIJAJXLWXVQIALM-UHFFFAOYSA-N

CAS号2410957-73-0

关联

100 项与 NCT-547 相关的临床结果

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100 项与 NCT-547 相关的转化医学

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100 项与 NCT-547 相关的专利（医药）

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1

项与 NCT-547 相关的文献（医药）

2020-12-01·Molecular Cancer

A novel HSP90 inhibitor targeting the C-terminal domain attenuates trastuzumab resistance in HER2-positive breast cancer

Letter

作者: Farrand, Lee ; Lee, Jeewoo ; Park, Hyun-Ju ; Park, Minsu ; Seo, Jae Hong ; Nguyen, Cong-Truong ; Kim, Yoon-Jae ; Kim, Ji Young ; Park, Jung Min ; Nam, Gibeom ; Park, Soeun ; Ann, Jihyae

AbstractTrastuzumab resistance in HER2-positive breast cancer is associated with a poorer prognosis. HSP90 is thought to play a major role in such resistance, but N-terminal inhibitors of this target have had little success. We sought to investigate the utility of NCT-547, a novel, rationally-designed C-terminal HSP90 inhibitor in the context of overcoming trastuzumab resistance. NCT-547 treatment significantly induced apoptosis without triggering the heat shock response (HSR), accompanied by caspase-3/− 7 activation in both trastuzumab-sensitive and -resistant cells. NCT-547 effectively promoted the degradation of full-length HER2 and truncated p95HER2, while also attenuating hetero-dimerization of HER2 family members. The impairment of cancer stem-like traits was observed with reductions in ALDH1 activity, the CD24low/CD44high subpopulation, and mammosphere formation in vitro and in vivo. NCT-547 was an effective inhibitor of tumor growth and angiogenesis, and no toxic outcomes were found in initial hepatic and renal analysis. Our findings suggest that NCT-547 may have applications in addressing trastuzumab resistance in HER2-positive breast cancer.

100 项与 NCT-547 相关的药物交易

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