IDO1 inhibitors by themselves have shitty response rates in human cancer trials, but you’d expect that, given that IDO1 is only one of three enzymes catalyzing the same step in tryptophan/kynurenine metabolism!https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6068130/ …
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Why? Tryptophan depletion is itself an immune defense against some bacteria and viruses. In response to viral infection, the body produces IFN-gamma, which activates IDO and TDO, which make kynurenine. Unfortunately, kynurenine has all the nasty effects mentioned upthread.
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So if you have a *chronic* viral infection, you’re going to keep pumping out kynurenines as a side effect of trying to kill the virus, which cause immunosuppression, which makes you more susceptible to viral infection...it’s a vicious cycle!
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What kinds of drugs inhibit IDO and TDO? Well, azole antifungals (like ketoconazole) and the MAOI antifungal phenelzine (also known as Nardil, the Flame of the West) https://scholar.google.com/scholar?start=20&q=ido1+inhibitor&hl=en&as_sdt=0,5#d=gs_qabs&u=%23p%3DYbQyk8FoSIMJ …
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The antiviral acyclovir is also an IDO1 inhibitor:https://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-7-44 …
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Acyclovir inhibits TDO too:https://link.springer.com/article/10.1007%2Fs11011-008-9095-4 …
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And so does the antibiotic minocycline:https://www.sciencedirect.com/science/article/abs/pii/S1043466617303848 …
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