CP21

CP21 is an iron chelator that binds to iron in a 3:1 (ligand:iron) ratio.¹ It is active against P. falciparum when used at concentrations of 10 and 100 µM.² CP21 inhibits production of prostaglandin I₂ induced by epinephrine, arachidonic acid , or A23187 in isolated rat aortic rings with IC₅₀ values of 1.3, 1.3, and 1.4 mM, respectively.³ It inhibits glutamate-induced oxytosis, as well as decreases iodoacetic acid-induced cytotoxicity in an in vitro model of ischemia, in HT22 mouse hippocampal cells (EC₅₀s = 13 and 9.5 µM, respectively).⁴ CP21 (200 mg/kg) increases the excretion of iron, but not copper, zinc, calcium, or magnesium, in rabbits.⁵

1.Dobbin, P.S., Hider, R.C., Hall, A.D., et al.Synthesis, physicochemical properties, and biological evaluation of N-substituted 2-alkyl-3-hydroxy-4(1H)-pyridinones: Orally active iron chelators with clinical potentialJ. Med. Chem.36(17)2448-2458(1993) 2.Heppner, D.G., Hallaway, P.E., Kontoghiorghes, G.J., et al.Antimalarial properties of orally active iron chelatorsBlood72(1)358-361(1988) 3.Jeremy, J.Y., Kontoghiorghes, G.J., Hoffbrand, A.V., et al.The iron chelators desferrioxamine and 1-alkyl-2-methyl-3-hydroxypyrid-4-ones inhibit vascular prostacyclin synthesis in vitroBiochem. J.254(1)239-244(1988) 4.Maher, P., and Kontoghiorghes, G.J.Characterization of the neuroprotective potential of derivatives of the iron chelating drug deferiproneNeurochem. Res.40(3)609-620(2015) 5.Kontoghiorghes, G.J., and Hoffbrand, A.V.Orally active α-ketohydroxy pyridine iron chelators intended for clinical use: In vivo studies in rabbitsBr. J. Haematol.62(4)607-613(1986)