IDO Inhibitor

IDO Inhibitor

IDO, also referred to indoleamine 2,3-dioxygenase, is an enzyme that plays a role in suppressing the immune system through catalyzing the oxidative cleavage of Tryptophan because T cells undergoing antigen-dependent activation require tryptophan for cell proliferation and survival. IDO inhibitors may help to promote an enhanced immune response against the tumor by blocking the IDO enzyme which reduces the depletion of tryptophan.

Within the human body there is a very intricate and sensitive balance that must be maintained for a person to remain healthy. When this balance is disrupted by an illness or disorder, chaos can result; this is especially true for cancer. Cancer cells possess some rather unique qualities compared to those associated with more benign diseases. It is these special characteristics that make cancer very destructive. Some of these distinctive characteristics include immortalization, insensitivity to growth inhibitory signals, invasion metastasis, apoptosis resistance, and immune escape . Immune escape refers to the ability of tumors to go undetected by the body, despite exhibiting immunogenic tumor antigens. Acquired tolerance of some antigens may be a welcomed effect in certain situations, however acquired tolerance to tumors is detrimental and potentially deadly to the host. One strategy employed by cancer cells has actually been adopted from a mechanism that normally exists to prevent a maternal immune response to fetal antigens present during gestation. A key component in this mechanism is the enzyme indoleamine 2,3-dioxygenase (IDO). IDO is a heme-containing extrahepatic enzyme that catalyzes the initial and rate limiting step of tryptophan catabolism along the kynurenine pathway, ultimately leading to the biosynthesis of nictoinamide adenine dinucleotide (NAD+).

Recent studies have been aimed at discovering why IDO becomes deregulated in cancer cells. Several experiments point to the gene BIN1 as potentially playing a key role in immunosuppression. BIN1 is a , 1-methyl-D-tryptophan, Newlinks’ restricted phenylimidazole NLG919. Nonetheless, the novelty and tremendous potential therapeutic benefit from IDO inhibitions argues for continuing the pursuit of potent and biocompatible IDO inhibitors.

Reference:Maria Winters, Design and Synthesis of Hydroxylamine Derivatives as Indoleamine-2,3-Dioxygenase Inhibitors

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