Inhibition of immunosuppressive indoleamine 2, 3-dioxygenase by targeting the heme and apo-form. Issue 3 (16th December 2020)

• Record Type: Journal Article
• Authors: Pradhan, Nirmalya; Akhtar, Nasim; Nath, Barnali; Peña-García, Jorge; Gupta, Anjali; Pérez-Sánchez, Horacio; Kumar, Sachin; Manna, Debasis
• Is Part Of: Chemical communications. Volume 57:Issue 3(2021)
• Page Start: 395
• Page End: 398
• Publication Date: 2020-12-16
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1039/d0cc06942f
• Languages: English
• ISSNs: 1359-7345

Abstract

Abstract : Antimalarial to immunomodulator: the potent quinine derivatives not only bind to apo-IDO1 but also undergo complexation with the free heme and perturb its rebinding, which could provide an inimitable advantage over other reported IDO1 inhibitors. Abstract : 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.