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- Chem Commun (Camb) 2020-12;
Inhibition of immunosuppressive indoleamine 2,3-dioxygenase by targeting the heme and apo-form
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… The cDNA of human IDO1 (hIDO1), synthesized by GenScript, was cloned into pET28a vectors containing a thrombin-cleavable N-terminal 6 × His-tag … Briefly, 100 nM holo-IDO1 in 100 mM potassium phosphate buffer (pH 7.2) plus 1 mM CHAPS supplemented with 0.5% (v:v … | |
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.
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