Z433927330(Z433927330) - 药物靶点：AQP7_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

AQP7

作用机制

AQP7 inhibitors(aquaporin 7 inhibitors)

治疗领域-

在研适应症-

非在研适应症-

原研机构

University of Lund

在研机构

University of Lund

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 Z433927330 相关的临床结果

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100 项与 Z433927330 相关的转化医学

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100 项与 Z433927330 相关的专利（医药）

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2

项与 Z433927330 相关的文献（医药）

Cancers

Evaluation of the Mammalian Aquaporin Inhibitors Auphen and Z433927330 in Treating Breast Cancer

Article

作者: Wang, Man ; Nannapaneni, Dharma T. ; Ashfeld, Brandon L. ; Tan, Elijah ; Arias-Matus, Carlos Eduardo ; Littlepage, Laurie E. ; Wu, Junmin ; Miranda-Vergara, Maria Cristina ; Lee, Mijoon ; Li, Jun ; Blagg, Brian S. J. ; Tennakoon, Parinda ; Charlestin, Verodia ; Kaliney, William

AQPs contribute to breast cancer progression and metastasis. We previously found that genetic inhibition of Aqp7 reduces primary tumor burden and metastasis in breast cancer. In this study, we utilized two AQP inhibitors, Auphen and Z433927330, to evaluate the efficacy of therapeutic inhibition of AQPs in breast cancer treatment. The inhibitors were evaluated in breast cancer for both cytotoxicity and metabolic stability assays across both murine and human breast cancer cell lines. Both AQP inhibitors also affected the expression of other AQP transcripts and proteins, which demonstrates compensatory regulation between AQP family members. As a single agent, Auphen treatment in vivo extended overall survival but did not impact primary or metastatic tumor burden. However, Auphen treatment made cells more responsive to chemotherapy (doxorubicin) or endocrine treatment (tamoxifen, fulvestrant). In fact, treatment with Tamoxifen reduced overall AQP7 protein expression. RNA-seq of breast cancer cells treated with Auphen identified mitochondrial metabolism genes as impacted by Auphen and may contribute to reducing mammary tumor progression, lung metastasis, and increased therapeutic efficacy of endocrine therapy in breast cancer. Interestingly, we found that Auphen and tamoxifen cooperate to reduce breast cancer cell viability, which suggests that Auphen treatment makes the cells more susceptible to Tamoxifen. Together, this study highlights AQPs as therapeutic vulnerabilities of breast cancer metastasis that are promising and should be exploited. However, the pharmacologic results suggest additional chemical refinements and optimization of AQP inhibition are needed to make these AQP inhibitors appropriate to use for therapeutic benefit in overcoming endocrine therapy resistance.

Cancers

Evaluation of the Mammalian Aquaporin Inhibitors Auphen and Z433927330 in Treating Breast Cancer

Article

作者: Wang, Man ; Nannapaneni, Dharma T. ; Ashfeld, Brandon L. ; Tan, Elijah ; Arias-Matus, Carlos Eduardo ; Littlepage, Laurie E. ; Wu, Junmin ; Miranda-Vergara, Maria Cristina ; Lee, Mijoon ; Li, Jun ; Blagg, Brian S. J. ; Tennakoon, Parinda ; Charlestin, Verodia ; Kaliney, William

AQPs contribute to breast cancer progression and metastasis. We previously found that genetic inhibition of Aqp7 reduces primary tumor burden and metastasis in breast cancer. In this study, we utilized two AQP inhibitors, Auphen and Z433927330, to evaluate the efficacy of therapeutic inhibition of AQPs in breast cancer treatment. The inhibitors were evaluated in breast cancer for both cytotoxicity and metabolic stability assays across both murine and human breast cancer cell lines. Both AQP inhibitors also affected the expression of other AQP transcripts and proteins, which demonstrates compensatory regulation between AQP family members. As a single agent, Auphen treatment in vivo extended overall survival but did not impact primary or metastatic tumor burden. However, Auphen treatment made cells more responsive to chemotherapy (doxorubicin) or endocrine treatment (tamoxifen, fulvestrant). In fact, treatment with Tamoxifen reduced overall AQP7 protein expression. RNA-seq of breast cancer cells treated with Auphen identified mitochondrial metabolism genes as impacted by Auphen and may contribute to reducing mammary tumor progression, lung metastasis, and increased therapeutic efficacy of endocrine therapy in breast cancer. Interestingly, we found that Auphen and tamoxifen cooperate to reduce breast cancer cell viability, which suggests that Auphen treatment makes the cells more susceptible to Tamoxifen. Together, this study highlights AQPs as therapeutic vulnerabilities of breast cancer metastasis that are promising and should be exploited. However, the pharmacologic results suggest additional chemical refinements and optimization of AQP inhibition are needed to make these AQP inhibitors appropriate to use for therapeutic benefit in overcoming endocrine therapy resistance.

100 项与 Z433927330 相关的药物交易

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