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Discovery of Novel 1,2,3-triazole Derivatives as IDO1 Inhibitors

Indoleamine 2,3-dioxygenase 1 (IDO1) has received much attention as an immunomodulatory enzyme in the field of cancer immunotherapy. While several IDO1 inhibitors have entered clinical trials, there are currently no IDO1 inhibitor drugs on the market. To explore potential IDO1 inhibitors, we designe...

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Detalles Bibliográficos
Autores principales: Hou, Xixi, Gong, Xiaoqing, Mao, Longfei, Zhao, Jie, Yang, Jianxue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695734/
https://www.ncbi.nlm.nih.gov/pubmed/36355488
http://dx.doi.org/10.3390/ph15111316
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author Hou, Xixi
Gong, Xiaoqing
Mao, Longfei
Zhao, Jie
Yang, Jianxue
author_facet Hou, Xixi
Gong, Xiaoqing
Mao, Longfei
Zhao, Jie
Yang, Jianxue
author_sort Hou, Xixi
collection PubMed
description Indoleamine 2,3-dioxygenase 1 (IDO1) has received much attention as an immunomodulatory enzyme in the field of cancer immunotherapy. While several IDO1 inhibitors have entered clinical trials, there are currently no IDO1 inhibitor drugs on the market. To explore potential IDO1 inhibitors, we designed a series of compounds with urea and 1,2,3-triazole structures. Organic synthesis and IDO1 enzymatic activity experiments verified the molecular-level activities of the designed compounds, and the IC(50) value of compound 3a was 0.75 μM. Molecular docking and quantum mechanical studies further explained the binding mode and reaction potential of compound 3a with IDO1. Our research has resulted in a series of novel IDO1 inhibitors, which is beneficial to the development of drugs targeting IDO1 in numerous cancer diseases.
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spelling pubmed-96957342022-11-26 Discovery of Novel 1,2,3-triazole Derivatives as IDO1 Inhibitors Hou, Xixi Gong, Xiaoqing Mao, Longfei Zhao, Jie Yang, Jianxue Pharmaceuticals (Basel) Article Indoleamine 2,3-dioxygenase 1 (IDO1) has received much attention as an immunomodulatory enzyme in the field of cancer immunotherapy. While several IDO1 inhibitors have entered clinical trials, there are currently no IDO1 inhibitor drugs on the market. To explore potential IDO1 inhibitors, we designed a series of compounds with urea and 1,2,3-triazole structures. Organic synthesis and IDO1 enzymatic activity experiments verified the molecular-level activities of the designed compounds, and the IC(50) value of compound 3a was 0.75 μM. Molecular docking and quantum mechanical studies further explained the binding mode and reaction potential of compound 3a with IDO1. Our research has resulted in a series of novel IDO1 inhibitors, which is beneficial to the development of drugs targeting IDO1 in numerous cancer diseases. MDPI 2022-10-25 /pmc/articles/PMC9695734/ /pubmed/36355488 http://dx.doi.org/10.3390/ph15111316 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hou, Xixi
Gong, Xiaoqing
Mao, Longfei
Zhao, Jie
Yang, Jianxue
Discovery of Novel 1,2,3-triazole Derivatives as IDO1 Inhibitors
title Discovery of Novel 1,2,3-triazole Derivatives as IDO1 Inhibitors
title_full Discovery of Novel 1,2,3-triazole Derivatives as IDO1 Inhibitors
title_fullStr Discovery of Novel 1,2,3-triazole Derivatives as IDO1 Inhibitors
title_full_unstemmed Discovery of Novel 1,2,3-triazole Derivatives as IDO1 Inhibitors
title_short Discovery of Novel 1,2,3-triazole Derivatives as IDO1 Inhibitors
title_sort discovery of novel 1,2,3-triazole derivatives as ido1 inhibitors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695734/
https://www.ncbi.nlm.nih.gov/pubmed/36355488
http://dx.doi.org/10.3390/ph15111316
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