Maccari Rosanna, Ottanà Rosaria
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno D'Alcontres, 31-98166 Messina, Italy.
J Med Chem. 2025 Jan 23;68(2):860-885. doi: 10.1021/acs.jmedchem.4c01116. Epub 2025 Jan 5.
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.
醛酮还原酶1B10（AKR1B10）是一种人类酶，可催化NADPH依赖性地将几种不同的羰基化合物还原为相应的醇。在生理条件下，AKR1B10主要在胃肠道中表达，在那里它可以对源自饮食来源和外源性物质的活性羰基化合物进行解毒。AKR1B10在几种癌症和癌前病变中高度表达，事实证明它在致癌过程中起着关键作用，并作为肿瘤发展的预后指标。此外，AKR1B10的上调与对已知抗癌药物的获得性耐药性密切相关。这种酶的高水平也与非癌性疾病的发病机制相关，如皮肤病变和COVID-19并发症。因此，在过去二十年中，AKR1B10作为一种能够对抗癌症和化疗耐药性的新型药物靶点引起了人们的关注，本文从药物化学的角度对其进行了探讨。
