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天然产物骨架作为设计和合成20S人蛋白酶体抑制剂的灵感来源。

Natural product scaffolds as inspiration for the design and synthesis of 20S human proteasome inhibitors.

作者信息

Hubbell Grace E, Tepe Jetze J

机构信息

Department of Chemistry, Michigan State University, East Lansing, MI 48823.

出版信息

RSC Chem Biol. 2020 Dec 1;1(5):305-332. doi: 10.1039/d0cb00111b. Epub 2020 Sep 16.

DOI:10.1039/d0cb00111b
PMID:33791679
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8009326/
Abstract

The 20S proteasome is a valuable target for the treatment of a number of diseases including cancer, neurodegenerative disease, and parasitic infection. In an effort to discover novel inhibitors of the 20S proteasome, many reseaarchers have looked to natural products as potential leads for drug discovery. The following review discusses the efforts made in the field to isolate and identify natural products as inhibitors of the proteasome. In addition, we describe some of the modifications made to natural products in order to discover more potent and selective inhibitors for potential disease treatment.

摘要

20S蛋白酶体是治疗包括癌症、神经退行性疾病和寄生虫感染在内的多种疾病的重要靶点。为了发现20S蛋白酶体的新型抑制剂，许多研究人员将天然产物视为药物发现的潜在先导物。以下综述讨论了该领域为分离和鉴定作为蛋白酶体抑制剂的天然产物所做的努力。此外，我们还描述了对天然产物进行的一些修饰，以便发现更有效和更具选择性的抑制剂用于潜在的疾病治疗。

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Leuk Res. 2020 Jan;88:106271. doi: 10.1016/j.leukres.2019.106271. Epub 2019 Nov 12.
3
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Int J Mol Sci. 2023 Feb 9;24(4):3525. doi: 10.3390/ijms24043525.
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