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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9695734 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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