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. It is selective for SPR over GTP cyclohydroxylase 1 (GCH1) in primary mouse dorsal root ganglia sensory neurons at 10 µM. 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. 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). 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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