Tin protoporphyrin IX dichloride

Tin protoporphyrin IX dichloride is a synthetic heme analog that selectively inhibits heme oxygenase 2 (HO-2) with IC50 value of 7.5 µM [1]. 

HO-2, widely expressed with high concentrations in the brain, is one of two forms of HO (HO-1 and HO-2). HO is responsible for converting heme to biliverdin, and carbon monoxide (CO), which has been implicated as a biological messenger molecule analogous to nitric oxide (NO) with endothelial-derived relaxing activity [1]. 

Tin protoporphyrin IX dichloride is a selective inhibitor of HO with ~ 10-fold selectivity for HO over endothelial nitric oxide synthase (NOS) and soluble guanylyl cyclase (IC50s = 35 and 30 nM, respectively). Tin protoporphyrin IX dichloride (1 ~ 100 µM) reduced acetylcholine (Ach)-induced endothelial-derived relaxation of porcine distal pulmonary arteries in the presence of N^w-nitro-Larginine methyl ester (L-NAME), with an IC50 of 7.6 µM [1]. 

In Sprague-Dawley rat neonates, a single subcutaneous injection of Tin protoporphyrin IX dichloride (100 µmol/kg) at birth, 12, 24, 48, and 72 hr later, blocked the postnatal increase in heme oxygenase activity that occurs in various tissues. Tin protoporphyrin IX dichloride administration also entirely prevented the development of hyperbilirubinemia that normally occurs postnatally [2]. 

References:

[1]. 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, 1996, 93(2): 795-798.

[2]. Drummond G S, 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, 1981, 78(10): 6466-6470.