Tin protoporphyrin IX dichloride (Synonyms: NSC 267099, SnPPIX)

Heme oxygenase (HO) converts protoheme to biliverdin, which in turn is enzymatically metabolized to bilirubin. While HO-2 is constitutively expressed, HO-1 can be induced by its heme substrate as well as by heavy metals, oxidizing agents, and other environmental stresses.[1],[2],[3] Tin protoporphyrin IX (SnPPIX) is a synthetic heme analog that selectively inhibits HO-1 (Ki = 11 nM) over HO-2 (IC50 = 7.5 µM).[4],[5] It also weakly inhibits endothelial nitric oxide synthase and soluble guanylyl cyclase (IC50s = 35 and 30 nM, respectively).[5] SnPPIX prevents hyperbilirubinemia in neonates by blocking HO-1 activity that increases postnatally.[4] It is rapidly cleared from plasma and persists in certain tissues, including kidney, liver, and spleen.[6] SnPPIX is commonly used as a tool to study the role of HO-1 activity in cells and in animals.[7[,[8]

Reference:
[1]. Kim, A.N., Jeon, W.K., Lee, J.J., et al. Up-regulation of heme oxygenase-1 expression through CaMKII-ERK1/2-Nrf2 signaling mediates the anti-inflammatory effect of bisdemethoxycurcumin in LPS-stimulated macrophages. Free Radical Biology & Medicine 49(3), 323-331 (2010).
[2]. Cable, E.E., Gildemeister, O.S., Pepe, J.A., et al. Mechanism of induction of heme oxygenase by metalloporphyrins in primary chick embryo liver cells: Evidence against a stress-mediated response. Molecular and Cellular Biochemistry 169, 13-20 (1997).
[3]. Surh, Y.J., Kundu, J.K., Li, M.H., et al. Role of Nrf2-mediated heme oxygenase-1 upregulation in adaptive survival response to nitrosative stress. Archives of Pharmacal Research 32(8), 1163-1176 (2009).
[4]. Drummond, G.S., and Kappas, A. Prevention of neonatal hyperbilirubinemia by tin protoporphyrin IX, a potent competitive inhibitor of heme oxidation. Proceedings of the National Academy of Sciences of the United States of America 78(10), 6466-6470 (1981).
[5]. Zakhary, R., Gaine, S.P., Dinerman, J.L., et al. Heme oxygenase 2: Endothelial and neuronal localization and role in endothelium-dependent relaxation. Proceedings of the National Academy of Sciences of the United States of America 93(2), 795-798 (1996).
[6]. Anderson, K.E., Simionatto, C.S., Drummond, G.S., et al. Tissue distribution and disposition of tin-protoporphyrin, a potent competitive inhibitor of heme oxygenase. Journal of Pharmacology and Experimental Therapeutics 228(2), 327-333 (1984).
[7]. Byun, S.J., Son, Y., and Pae, H.O. Cytoprotective effect of β-lapachone by inducing heme oxygenase-1 expression and AMP-activated protein kinase activation in human endothelial cells. Eur.Rev.Med.Pharmacol.Sci. 18(7), 949-958 (2014).
[8]. Zhang, M., Wang, S., Mao, L., et al. Omega-3 fatty acids protect the brain against ischemic injury by activating Nrf2 and upregulating heme oxygenase 1. Journal of Neuroscience 34(5), 1903-1915 (2014).