As a rate-limiting enzyme in the major pathway of l-tryptophan catabolism, indoleamine 2, 3-dioxygenase 1 (IDO1) has been regarded as a potential target for the treatment of a variety of diseases. To identify the key molecular features and extend the structural variety of IDO1 inhibitors, a ferrous binding group (FBG)-based 3D-QSAR pharmacophore model was constructed, validated and used for virtual screening herein. The Specs database was initially filtered based on drug-like rules, and was subsequently screened by the pharmacophore model. Molecular docking simulations and similarity analysis were then followed to prioritize twenty compounds for biological tests. Among them, compound VS-13 exhibited moderate inhibitory activity against IDO1, and could be subjected to further structure-activity relationship studies and structural optimization.

作为1-色氨酸分解代谢的主要途径中的限速酶，吲哚胺2，3-二加氧酶1（IDO1）被认为是治疗多种疾病的潜在靶标。为了鉴定关键的分子特征并扩展IDO1抑制剂的结构种类，构建，验证了基于铁结合基（FBG）的3D-QSAR药效团模型，并将其用于此处的虚拟筛选。首先根据类似药物的规则过滤Specs数据库，然后通过药效基团模型进行筛选。然后进行分子对接模拟和相似性分析，以区分20种化合物的生物检测优先级。其中，复合VS-13 表现出对IDO1的中等抑制活性，可以进行进一步的构效关系研究和结构优化。