A novel series of human dihydroorotate dehydrogenase inhibitors discovered by in vitro screening: inhibition activity and crystallographic binding mode

A novel series of human dihydroorotate dehydrogenase inhibitors discovered by in vitro screening: inhibition activity and crystallographic binding mode

Human dihydroorotate dehydrogenase (DHODH), the enzyme that catalyzes the rate‐limiting step in de novo pyrimidine biosynthesis, is considered to be an attractive target for potential treatment of autoimmune disease and cancer. Here, we present a novel class of human DHODH inhibitors with high inhib...

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Bibliographic Details
Main Authors: Ting Zeng, Zeping Zuo, Youfu Luo, Yinglan Zhao, Yamei Yu, Qiang Chen
Format: Article
Language:English
Published: Wiley 2019-08-01
Series:FEBS Open Bio
Subjects:
crystal structure
dihydroorotate dehydrogenase
drug
inhibitor
pyrimidine biosynthesis
Online Access:https://doi.org/10.1002/2211-5463.12658
Description
Summary:Human dihydroorotate dehydrogenase (DHODH), the enzyme that catalyzes the rate‐limiting step in de novo pyrimidine biosynthesis, is considered to be an attractive target for potential treatment of autoimmune disease and cancer. Here, we present a novel class of human DHODH inhibitors with high inhibitory potency. The high‐resolution crystal structures of human DHODH complexed with various agents reveal the details of their interactions. Comparisons with the binding modes of teriflunomide and brequinar provide insights that may facilitate the development of new inhibitors targeting human DHODH.
ISSN:2211-5463

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