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Recently, researcher Wang Yonghui's team from the Department of Medicinal Chemistry, School of Pharmacy, Fudan University, in cooperation with Professor Huang Jin's team from the School of Pharmacy, East China University of Science and Technology, published a paper entitled "Discovery of Orally Available Retinoic Acid Receptor-Related Orphan in the Journal of Medicinal Chemistry, an authoritative journal in the field of medicinal chemistry.
Receptor γ-t/Dihydroorotate Dehydrogenase Dual Inhibitors for the Treatment of Refractory Inflammatory Bowel Disease" research paper, and selected as the cover article of the journal
.
This paper proposes a new strategy for the treatment of inflammatory bowel disease (IBD) with RORγt/DHODH dual-target inhibitors, and discovers a class of RORγt/DHODH dual-target inhibitors with a tetrahydrobenzothiazole nucleus, which can be used in vivo.
Overview of RORγt/DHODH dual-target inhibitor research
Inflammatory bowel disease (IBD) is a chronic disease of the digestive tract with complex etiology and easy recurrence mediated by immune abnormalities
.
In recent years, the incidence and prevalence of IBD have risen rapidly in developing countries.
The high recurrence and serious complications after treatment have brought great challenges to the clinical treatment of IBD
This study firstly verified the efficacy of the combination of RORγt inhibitor and DHODH inhibitor in the treatment of inflammatory bowel disease, and found that the combination has a synergistic therapeutic effect
.
Subsequently, a series of novel ROR γ t/DHODH dual-target inhibitors were designed and synthesized, and it was found that they could not only reduce the differentiation of Th17 cells, but also reduce the expansion and activation of T cells, so that the two targets act synergistically and play an anti-inflammatory role.
Chen Ji'an, a 2019 doctoral student of the Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Ma Hui and Liu Zehui, graduate students of the School of Pharmacy, East China University of Science and Technology are the co-first authors of this article; Researcher Wang Yonghui, Associate Professor Xie Qiong, and Professor Huang Jin of East China University of Science and Technology are the researcher of the School of Pharmacy, Fudan University.
co-corresponding author
.
The research was funded by the National Natural Science Foundation of China, the Shanghai Natural Science Foundation, and the Personalized Support Project for Original Research of the School of Pharmacy
Original link: https://doi.
org/10.
1021/acs.
jmedchem.
1c01746
Introduction of Wang Yonghui's research group
The research group of researcher Wang Yonghui from the Department of Medicinal Chemistry, School of Pharmacy, Fudan University currently has 1 specially-appointed researcher, 2 associate professors, 4 doctoral students and 4 master students
.
The main research direction is the discovery and research of autoimmune and tumor immune small molecule drugs
