寻找人类醛酮还原酶1B10 （AKR1B10）抑制剂作为抗癌和化疗耐药的新药物：最新进展和前景

IF 6.8 1区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Medicinal Chemistry Pub Date : 2025-01-05 DOI:10.1021/acs.jmedchem.4c01116

Rosanna Maccari, Rosaria Ottanà

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引用次数: 0

摘要

醛酮还原酶 1B10 (AKR1B10) 是一种人类酶，它能催化 NADPH 将几种不同的羰基化合物还原成相应的醇。在生理条件下，AKR1B10 主要在胃肠道中表达，它能对来自食物和异种生物的活性羰基化合物进行解毒。AKR1B10 在多种癌症和癌前病变中高度表达，被证明与癌变有重要关系，并可作为肿瘤发展的预后指标。此外，AKR1B10 的上调与已知抗癌药物的获得性抗药性密切相关。这种酶的高水平也与非癌症疾病的发病机制有关，如皮肤病变和 COVID-19 并发症。因此，在过去的二十年中，AKR1B10 作为一种新型靶点引起了人们的兴趣，这种靶点可以同时对抗癌症和化疗耐药性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

In Search for Inhibitors of Human Aldo-Keto Reductase 1B10 (AKR1B10) as Novel Agents to Fight Cancer and Chemoresistance: Current State-of-the-Art and Prospects

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In Search for Inhibitors of Human Aldo-Keto Reductase 1B10 (AKR1B10) as Novel Agents to Fight Cancer and Chemoresistance: Current State-of-the-Art and Prospects

Aldo-keto reductase 1B10 (AKR1B10) is a human enzyme that catalyzes the NADPH-dependent reduction of several different carbonyl compounds to the corresponding alcohols. Under physiological conditions, AKR1B10 is expressed mainly in the gastrointestinal tract, where it can detoxify reactive carbonyl compounds derived from dietary sources and xenobiotics. AKR1B10 is highly expressed in several cancers and precancerous conditions, proving to be crucially implicated in carcinogenesis and to function as a prognostic indicator of tumor development. Moreover, AKR1B10 up-regulation is strictly related to acquired resistance to known anticancer drugs. High levels of this enzyme are also correlated to the pathogenesis of noncancerous diseases, such as skin pathologies and COVID-19 complications. Therefore, in the last two decades, AKR1B10 has attracted interest as a novel target for agents able to fight both cancer and chemoresistance, and here, it is explored from a medicinal chemistry perspective.

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来源期刊

Journal of Medicinal Chemistry 医学-医药化学

CiteScore

4.00

自引率

11.00%

发文量

804

审稿时长

1.9 months

期刊介绍： The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents. The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.