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碳酸酐酶 IX 抑制剂 4-[4-(4-苯并[1,3]二恶唑-5-基甲基-哌嗪-1-基)-亚苄基-肼羰基]-苯磺酰胺 (BSM-0004) 的抗乳腺癌作用:体内和体外研究。

Anti-breast cancer action of carbonic anhydrase IX inhibitor 4-[4-(4-Benzo[1,3]dioxol-5-ylmethyl-piperazin-1-yl)-benzylidene-hydrazinocarbonyl]-benzenesulfonamide (BSM-0004): and studies.

机构信息

College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.

Department of Biosystem, Molecular Cancer Biology Laboratory, Cellular Heterogeneity Research Center, Sookmyung Women's University, Seoul, Republic of Korea.

出版信息

J Enzyme Inhib Med Chem. 2021 Dec;36(1):954-963. doi: 10.1080/14756366.2021.1909580.

Abstract

Anti-breast cancer action of novel human carbonic anhydrase IX (hCA IX) inhibitor BSM-0004 has been investigated using and models of breast cancer. BSM-0004 was found to be a potent and selective hCA IX inhibitor with a Ki value of 96 nM. anticancer effect of BSM-0004 was analysed against MCF 7 and MDA-MA-231 cells, BSM-0004 exerted an effective cytotoxic effect under normoxic and hypoxic conditions, inducing apoptosis in MCF 7 cells. Additionally, this compound significantly regulates the expression of crucial biomarkers associated with apoptosis. The investigation was extended to confirm the efficacy of this hCA IX inhibitor against model of breast cancer. The results specified that the treatment of BSM-0004 displayed an effective anticancer effect, reducing tumour growth in a xenograft cancer model. Hence, our investigation delivers an effective anti-breast cancer agent that engenders the anticancer effect by inhibiting hCA IX.

摘要

新型人碳酸酐酶 IX(hCAIX)抑制剂 BSM-0004 的抗乳腺癌作用已在乳腺癌的 和 模型中进行了研究。发现 BSM-0004 是一种有效的、选择性的 hCAIX 抑制剂,Ki 值为 96nM。针对 MCF7 和 MDA-MA-231 细胞分析了 BSM-0004 的抗癌作用,BSM-0004 在常氧和低氧条件下均能发挥有效的细胞毒性作用,诱导 MCF7 细胞凋亡。此外,该化合物还显著调节与凋亡相关的关键生物标志物的表达。进一步的研究证实了该 hCAIX 抑制剂对乳腺癌 模型的疗效。结果表明,BSM-0004 的治疗在异种移植癌症模型中显示出有效的抗癌作用,可减少肿瘤生长。因此,我们的研究提供了一种有效的抗乳腺癌药物,通过抑制 hCAIX 发挥抗癌作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bcf/8118463/eae020f0884e/IENZ_A_1909580_F0001_C.jpg

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