N-[2-(5-Hydroxy-2-methyl-1H-indol-3-yl)ethyl]-2-methoxyacetamide

SPR inhibitor 3 (SPRi3) is a potent sepiapterin reductase (SPR) inhibitor. SPR inhibitor 3 (SPRi3) displays high binding affinity to human SPR in a cell-free assay (IC50=74 nM) and efficiently reduces biopterin levels in a cell-based assay (IC50=5.2 μM). SPR inhibitor 3 (SPRi3) reduces neuropathic and inflammatory pain through a reduction of BH4 levels[1][2][3].

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[1] Latremoliere A, et al. Reduction of Neuropathic and Inflammatory Pain through Inhibition of the Tetrahydrobiopterin Pathway. Neuron. 2015 Jun 17;86(6):1393-406. DOI:10.1016/j.neuron.2015.05.033
[2] Cronin SJF, et al. The metabolite BH4 controls T cell proliferation in autoimmunity and cancer. Nature. 2018 Nov;563(7732):564-568. DOI:10.1038/s41586-018-0701-2
[3] Haruki H, et al. Tetrahydrobiopterin Biosynthesis as a Potential Target of the Kynurenine Pathway Metabolite Xanthurenic Acid. J Biol Chem. 2016 Jan 8;291(2):652-7. DOI:10.1074/jbc.C115.680488