Cayman SPRi 3

SPRi 3 is an inhibitor of sepiapterin reductase (SPR), an enzyme that catalyzes the formation of tetrahydrobiopterin (BH4), with IC₅₀ values of 62 and 14 nM for the recombinant human and rat enzymes, respectively.¹ It is selective for SPR over GTP cyclohydroxylase 1 (GCH1) in primary mouse dorsal root ganglia sensory neurons at 10 µM.² SPRi 3 (50 µM) inhibits proliferation of anti-CD3 and anti-CD28 antibody-stimulated isolated human peripheral blood mononuclear cells (PBMCs) or CD4⁺ T cells.³ Intraperitoneal administration of SPRi 3 (300 mg/kg) decreases brain BH4 levels and reduces mechanical allodynia in mouse models of peripheral neuropathy induced by spared nerve injury (SNI) or chronic constriction injury (CCI).² It also decreases macrophage infiltration and thermal hyperalgesia in the inflamed joints of a mouse model of rheumatoid arthritis induced by complete Freunds adjuvant (CFA) at the same dose.

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