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抑制碳酸酐酶 IX 和 XII 的活性作为开发新型抗癌药物的候选物选择标准。

Inhibitory activity against carbonic anhydrase IX and XII as a candidate selection criterion in the development of new anticancer agents.

机构信息

Institute of Chemistry, St. Petersburg State University, St. Petersburg, Russia.

Neurofarba Department, Section of Pharmaceutical Sciences, University of Florence, Florence, Italy.

出版信息

J Enzyme Inhib Med Chem. 2020 Dec;35(1):1555-1561. doi: 10.1080/14756366.2020.1801674.

Abstract

Analysis of the literature data reveals that while inhibition of cancer-related carbonic anhydrase IX and XII isoforms continues to be an important enrichment factor for designing anticancer agent development libraries, exclusive reliance on the inhibition of these two recombinant isozymes in nominating candidate compounds for evaluation of their effects on cancer cells may lead not only to identifying numerous compounds devoid of the desired cellular efficacy but also to overlooking many promising candidates which may not display the best potency in biochemical inhibition assay. However, SLC-0111, now in phase Ib/II clinical trials, was developed based on the excellent agreement between the , and more recently, in-patient data.

摘要

文献资料分析表明,虽然抑制与癌症相关的碳酸酐酶 IX 和 XII 同工型仍然是设计抗癌药物开发库的一个重要富集因素,但仅仅依赖于抑制这两种重组同工酶来提名候选化合物以评估它们对癌细胞的影响,不仅可能导致鉴定出许多缺乏所需细胞疗效的化合物,而且还可能忽略许多有前途的候选物,这些候选物在生化抑制测定中可能显示不出最佳的效力。然而,目前正在进行 Ib/II 期临床试验的 SLC-0111 是基于 、 和最近的住院患者数据之间的极好一致性而开发的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46b2/7470080/ab30dff824e2/IENZ_A_1801674_F0001_B.jpg

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