C16-AM-80(C16-AM-80) - 药物靶点：RARα x SIN3A_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

RARα x SIN3A

作用机制

RARα激动剂(维甲酸受体α激动剂)、SIN3A基因调节剂(SIN3 transcription regulator family member A gene modulators)

治疗领域

肿瘤

在研适应症

肿瘤

非在研适应症-

原研机构

Mount Sinai Medical Center of Florida, Inc.

在研机构

Mount Sinai Medical Center of Florida, Inc.

Stanford University School of Medicine

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 C16-AM-80 相关的临床结果

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100 项与 C16-AM-80 相关的转化医学

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100 项与 C16-AM-80 相关的专利（医药）

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1

项与 C16-AM-80 相关的文献（医药）

2016-07-12·Oncotarget

Blocking the PAH2 domain of Sin3A inhibits tumorigenesis and confers retinoid sensitivity in triple negative breast cancer

Article

作者: Cubedo, Elena ; Kane, Maureen ; Zelent, Arthur ; Waxman, Samuel ; Bansal, Nidhi ; Jones, Jace W. ; Leibovitch, Boris ; Pierzchalski, Keely ; Fishel, Melissa ; Bosch, Almudena ; Farias, Eduardo ; Pereira, Lutecia ; Yu, Jianshi

Triple negative breast cancer (TNBC) frequently relapses locally, regionally or as systemic metastases. Development of targeted therapy that offers significant survival benefit in TNBC is an unmet clinical need. We have previously reported that blocking interactions between PAH2 domain of chromatin regulator Sin3A and the Sin3 interaction domain (SID) containing proteins by SID decoys result in EMT reversal, and re-expression of genes associated with differentiation. Here we report a novel and therapeutically relevant combinatorial use of SID decoys. SID decoys activate RARα/β pathways that are enhanced in combination with RARα-selective agonist AM80 to induce morphogenesis and inhibit tumorsphere formation. These findings correlate with inhibition of mammary hyperplasia and a significant increase in tumor-free survival in MMTV-Myc oncomice treated with a small molecule mimetic of SID (C16). Further, in two well-established mouse TNBC models we show that treatment with C16-AM80 combination has marked anti-tumor effects, prevents lung metastases and seeding of tumor cells to bone marrow. This correlated to a remarkable 100% increase in disease-free survival with a possibility of "cure" in mice bearing a TNBC-like tumor. Targeting Sin3A by C16 alone or in combination with AM80 may thus be a promising adjuvant therapy for treating or preventing metastatic TNBC.

100 项与 C16-AM-80 相关的药物交易

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