Indian Institute of Technology Guwahati, Chemistry, Guwahati, Assam, India.
Chem Commun (Camb). 2021 Jan 14;57(3):395-398. doi: 10.1039/d0cc06942f.
Inhibition of immunomodulating enzyme indoleamine 2,3-dioxygenase 1 (IDO1) is considered one of the potential approaches in the fight against cancer and other diseases. Comprehensive biophysical and cellular studies have shown that quinine derivatives effectively inhibit the activity of IDO1. Mechanistic studies revealed that the potent quinine derivatives compete with heme for binding to apo-IDO1 and perturb its reversible binding propensity to apo-IDO1 via the formation of a heme-inhibitor complex. This IDO1 inhibitory pathway could provide new avenues to immunotherapy-based drug discovery strategies.
抑制免疫调节酶吲哚胺 2,3-双加氧酶 1（IDO1）被认为是对抗癌症和其他疾病的潜在方法之一。全面的生物物理和细胞研究表明，奎宁衍生物能有效抑制 IDO1 的活性。机制研究表明，强效的奎宁衍生物通过形成血红素-抑制剂复合物与脱辅基 IDO1 竞争结合血红素，并干扰其与脱辅基 IDO1 的可逆结合倾向。这种 IDO1 抑制途径可为基于免疫疗法的药物发现策略提供新途径。
