Beck Katharina R, Kaserer Teresa, Schuster Daniela, Odermatt Alex
Swiss Center for Applied Human Toxicology and Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
Institute of Pharmacy/Pharmaceutical Chemistry and Center for Molecular Biosciences Innsbruck (CMBI), Computer Aided Molecular Design Group, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
J Steroid Biochem Mol Biol. 2017 Jul;171:157-177. doi: 10.1016/j.jsbmb.2017.03.008. Epub 2017 Mar 9.
Several members of the short-chain dehydrogenase/reductase (SDR) enzyme family play fundamental roles in adrenal and gonadal steroidogenesis as well as in the metabolism of steroids, oxysterols, bile acids, and retinoids in peripheral tissues, thereby controlling the local activation of their cognate receptors. Some of these SDRs are considered as promising therapeutic targets, for example to treat estrogen-/androgen-dependent and corticosteroid-related diseases, whereas others are considered as anti-targets as their inhibition may lead to disturbances of endocrine functions, thereby contributing to the development and progression of diseases. Nevertheless, the physiological functions of about half of all SDR members are still unknown. In this respect, in silico tools are highly valuable in drug discovery for lead molecule identification, in toxicology screenings to facilitate the identification of hazardous chemicals, and in fundamental research for substrate identification and enzyme characterization. Regarding SDRs, computational methods have been employed for a variety of applications including drug discovery, enzyme characterization and substrate identification, as well as identification of potential endocrine disrupting chemicals (EDC). This review provides an overview of the efforts undertaken in the field of virtual screening supported identification of bioactive molecules in SDR research. In addition, it presents an outlook and addresses the opportunities and limitations of computational modeling and in vitro validation methods.
短链脱氢酶/还原酶（SDR）酶家族的几个成员在肾上腺和性腺类固醇生成以及外周组织中类固醇、氧固醇、胆汁酸和类视黄醇的代谢中发挥着重要作用，从而控制其同源受体的局部激活。其中一些SDR被认为是有前景的治疗靶点，例如用于治疗雌激素/雄激素依赖性和皮质类固醇相关疾病，而其他一些则被视为抗靶点，因为抑制它们可能导致内分泌功能紊乱，从而促进疾病的发生和发展。然而，所有SDR成员中约有一半的生理功能仍然未知。在这方面，计算机工具在药物发现中用于识别先导分子、在毒理学筛选中促进危险化学品的识别以及在基础研究中用于底物识别和酶表征方面具有很高的价值。关于SDR，计算方法已被用于多种应用，包括药物发现、酶表征和底物识别，以及潜在内分泌干扰化学物质（EDC）的识别。本综述概述了在虚拟筛选支持下的SDR研究中生物活性分子识别领域所做的努力。此外，它还展望了计算建模和体外验证方法的机遇和局限性。
