Overview of human 20 alpha-hydroxysteroid dehydrogenase (AKR1C1): Functions, regulation, and structural insights of inhibitors
Overview of human 20 alpha-hydroxysteroid dehydrogenase (AKR1C1): Functions, regulation, and structural insights of inhibitors
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DOI：
10.1016/j.cbi.2021.109746
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发表时间：
2022-01-05
影响因子：
5.1
通讯作者：
Sun, Haopeng
中科院分区：
文献类型：
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作者：
Chu, Xianglin;He, Siyu;Sun, Haopeng
人醛酮还原酶家族1c1(AKR1c1)是参与人体激素代谢的重要酶，主要负责孕酮在人体内的代谢。AKR1C1基因高表达，与多种疾病的发生发展有重要关系，特别是与激素代谢相关的某些癌症。目前已经发现了许多AKR1C1的抑制剂，包括一些人工合成的化合物和天然产物，它们对AKR1C1具有一定的靶向抑制活性。本文简要综述了AKR1C1的生理病理功能及其与疾病的关系，综述了AKR1C1抑制剂的研究进展，并通过分子对接结果和已有的共晶结构阐明了抑制剂与AKR1C1的相互作用。最后，我们从AKR1C1结构的角度讨论了选择性AKR1C1抑制剂的设计思想，从生物标志物、受体前调节和单核苷酸多态性等方面探讨了AKR1C1在人类疾病治疗中的应用前景，旨在为针对AKR1C1的药物研究提供新的思路。
Human aldo-keto reductase family 1C1 (AKR1C1) is an important enzyme involved in human hormone metabolism, which is mainly responsible for the metabolism of progesterone in the human body. AKR1C1 is highly expressed and has an important relationship with the occurrence and development of various diseases, especially some cancers related to hormone metabolism. Nowadays, many inhibitors against AKR1C1 have been discovered, including some synthetic compounds and natural products, which have certain inhibitory activity against AKR1C1 at the target level. Here we briefly reviewed the physiological and pathological functions of AKR1C1 and the relationship with the disease, and then summarized the development of AKR1C1 inhibitors, elucidated the interaction between inhibitors and AKR1C1 through molecular docking results and existing co-crystal structures. Finally, we discussed the design ideals of selective AKR1C1 inhibitors from the perspective of AKR1C1 structure, discussed the prospects of AKR1C1 in the treatment of human diseases in terms of biomarkers, pre-receptor regulation and single nucleotide polymorphisms, aiming to provide new ideas for drug research targeting AKR1C1.