UPF-648 is an inhibitor of kynurenine 3-monooxygenase (IC50 = 40 nM).1 It increases kynurenine and kynurenic acid and decreases 3-hydroxykynurenine brain levels in newborn rats for up to 12 hours when administered at a dose of 30 mg/kg.2 UPF-648 (30 ?M) is protective against rhabdomere neurodegeneration in the eye in a Drosophila model of Huntington's disease.3 It also decreases hypersensitivity to mechanical and thermal stimuli in a rat model of neuropathic pain induced by chronic constriction injury to the sciatic nerve.4
1.Pellicciari, R., Amori, L., Costantino, G., et al.Modulation of the kynurine pathway of tryptophan metabolism in search for neuroprotective agents. Focus on kynurenine-3-hydroxylaseAdv. Exp. Med. Biol.527621-628(2003) 2.Ceresoli-Borroni, G., Guidetti, P., Amori, L., et al.Perinatal kynurenine 3-hydroxylase inhibition in rodents: Pathophysiological implicationsJ. Neurosci. Res.85(4)845-854(2007) 3.Campesan, S., Green, E.W., Breda, C., et al.The kynurenine pathway modulates neurodegeneration in a Drosophila model of Huntington's diseaseCurr. Biol.21(11)9611-9966(2011) 4.Rojewska, E., Ciapa?a, K., Piotrowska, A., et al.Pharmacological inhibition of indoleamine 2,3-dioxygenase-2 and kynurenine 3-monooxygenase, enzymes of the kynurenine pathway, significantly diminishes neuropathic pain in a rat modelFront. Pharmacol.9724(2018)