Molecular Modeling Group, SIB Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland.
Department of Oncology, University Hospital of Lausanne (CHUV), Ludwig Cancer Research─Lausanne Branch, 1011 Lausanne, Switzerland.
J Med Chem. 2021 Dec 23;64(24):17690-17705. doi: 10.1021/acs.jmedchem.1c01665. Epub 2021 Dec 15.
Since the discovery of the implication of indoleamine 2,3-dioxygenase 1 (IDO1) in tumoral immune resistance in 2003, the search for inhibitors has been intensely pursued both in academia and in pharmaceutical companies, supported by the publication of the first crystal structure of IDO1 in 2006. More recently, it has become clear that IDO1 is an important player in various biological pathways and diseases ranging from neurodegenerative diseases to infection and autoimmunity. Its inhibition may lead to clinical benefit in different therapeutic settings. At present, over 50 experimental structures of IDO1 in complex with different ligands are available in the Protein Data Bank. Our analysis of this wealth of structural data sheds new light on several open issues regarding IDO1's structure and function.
自 2003 年发现吲哚胺 2,3-双加氧酶 1（IDO1）在肿瘤免疫抵抗中的作用以来，学术界和制药公司都在积极寻找 IDO1 的抑制剂，这得益于 2006 年首次公布的 IDO1 的晶体结构。最近，人们越来越清楚地认识到 IDO1 是从神经退行性疾病到感染和自身免疫等各种生物途径和疾病中的重要参与者。其抑制可能会在不同的治疗环境中带来临床获益。目前，蛋白质数据库中已有超过 50 种 IDO1 与不同配体结合的实验结构。我们对这些丰富的结构数据的分析为 IDO1 的结构和功能的几个悬而未决的问题提供了新的线索。
