%0 Journal Article %T AKR1C3与疾病的关系
The Relationship between AKR1C3 and Diseases %A 袁大中 %A 宋冰茹 %J Hans Journal of Medicinal Chemistry %P 70-85 %@ 2331-8295 %D 2025 %I Hans Publishing %R 10.12677/hjmce.2025.131008 %X 醛酮还原酶家族1成员C3 (AKR1C3)，也被称为5型17β羟基类固醇脱氢酶(17β-HSD5)或前列腺素F (PGF)合成酶，在雄激素生物合成中起关键作用。它催化弱雄激素、雌酮(弱雌激素)和PGD2分别转化为强雄激素(睾酮和5α-二氢睾酮)、17β-雌二醇(强雌激素)和11β-PGF2α。AKR1C3水平升高激活雄激素受体(AR) 8信号通路，促进肿瘤复发和对癌症治疗产生耐药性。AKR1C3的过表达作为一种致癌因子，促进癌细胞的增殖、侵袭和转移，并与癌症患者的不良预后和总生存期相关。抑制AKR1C3已被证明在抑制肿瘤进展和克服治疗耐药性方面具有强大的功效。因此，AKR1C3抑制剂的开发和设计引起了研究人员越来越多的兴趣，近年来取得了重大进展。本文简要介绍了AKR1C3的生理和病理功能，并对近年来选择性AKR1C3抑制剂的研究进展进行了综述。我们的目的是为未来的药物发现和潜在的治疗前景提供参考，新的、有效的、选择性的AKR1C3抑制剂。
Aldo-Keto Reductase Family 1 Member C3 (AKR1C3), also known as type 5 17β-hydroxysteroid dehydrogenase (17β-HSD5) or prostaglandin F (PGF) synthase, functions as a pivotal enzyme in androgen biosynthesis. It catalyzes the conversion of weak androgens, estrone (a weak estrogen), and PGD2 into potent androgens (testosterone and 5α-dihydrotestosterone), 17β-estradiol (a potent estrogen), and 11β-PGF2α, respectively. Elevated levels of AKR1C3 activate androgen receptor (AR) signaling pathway, contributing to tumor recurrence and imparting resistance to cancer therapies. The overexpression of AKR1C3 serves as an oncogenic factor, promoting carcinoma cell proliferation, invasion, and metastasis, and is correlated with unfavorable prognosis and overall survival in carcinoma patients. Inhibiting AKR1C3 has demonstrated potent efficacy in suppressing tumor progression and overcoming treatment resistance. As a result, the development and design of AKR1C3 inhibitors have garnered increasing interest among researchers, with significant progress witnessed in recent years. Here, we briefly review the physiological and pathological function of AKR1C3 and then summarize the recent development of selective AKR1C3 inhibitors. We aim to provide a reference for future drug discovery and potential therapeutic perspectives on novel, potent, selective AKR1C3 inhibitors. %K AKR1C3， %K 癌症， %K 抑制剂， %K 治疗耐药
AKR1C3 %K Cancer %K Inhibitors %K Therapeutic Resistance %U http://www.hanspub.org/journal/PaperInformation.aspx?PaperID=107759