A sepiapterin reductase inhibitor
Potent sepiapterin reductase (SPR) inhibitor (IC50 = 53 - 74 nM for human SPR). Inhibits BH4 synthesis pathway and attenuates proliferation in naive CD4+ T cells. Suppresses proliferation of human effector CD4+ T cells following stimulation. Reduces SPR activity in mouse primary cultures of sensory neurons (IC50 = 450 nM). Ameliorates colitis, suppressing the intestinal infiltration of T cells and other immune cells in vivo. Also reduces immune-cell infiltration into mouse lungs. Reduces neuropathic and inflammatory pain in mouse models.
Haruki et al (2016) Tetrahydrobiopterin biosynthesis as a potential target of the kynurenine pathway metabolite xanthurenic acid. J.Biol.Chem. 291 652 PMID:26565027 |Latremoliere et al (2015) Reduction of neuropathic and inflammatory pain through inhibition of the tetrahydrobiopterin pathway. Neuron 86 1393 PMID:26087165 |Cronin et al (2018) The metabolite BH4 controls T cell proliferation in autoimmunity and cancer. Nature 563 564 PMID:30405245
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