Tin protoporphyrin IX dichloride

Tin protoporphyrin IX dichloride (SnPPIX) is a synthetic heme analog that selectively inhibits Heme oxygenase 1 (HO-1) (K_i = 11 nM) over HO-2 (IC₅₀ = 7.5 µM)^[1-2]. Tin protoporphyrin IX dichloride can weakly inhibit the activities of endothelial nitric oxide synthase and soluble guanylate cyclase with IC₅₀ values of 35 and 30 μM, respectively^[2]. Tin protoporphyrin IX dichloride is commonly used to study the role of HO-1 in cells and animals.

Tin protoporphyrin IX dichloride (0.5, 1, 5, 10 and 25 µM) treated 293T cells for 6 hours inhibited HO-1 activity in cells, but Tin protoporphyrin IX dichloride also upregulated HO-1 mRNA and protein levels^[3]. Tin protoporphyrin IX dichloride (10 µM) could inhibit HO-1 activity and induce HO-1 protein expression in mouse fibroblasts^[4]. In addition, 10 µM Tin protoporphyrin IX dichloride significantly increased HMOX1 mRNA levels in UOK 262 cells^[5].

Mice infected with aerosolized Mycobacterium tuberculosis and treated with Tin protoporphyrin IX dichloride (5 mg/kg) on the same day showed a significant reduction in lung bacterial burden at week 6. Similar effects were seen when Tin protoporphyrin IX dichloride was started in week 4 of infection^[6].

References:
[1] 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).
[2] 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).
[3] Mucha O, Podkalicka P, Czarnek M, et al. Pharmacological versus genetic inhibition of heme oxygenase-1: the comparison of metalloporphyrins, shRNA and CRISPR/Cas9 system[J]. 2018.
[4] Stepniewski J, Pacholczak T, Skrzypczyk A, et al. Heme oxygenase‐1 affects generation and spontaneous cardiac differentiation of induced pluripotent stem cells[J]. IUBMB life, 2018, 70(2): 129-142.
[5] Podkalicka P, Mucha O, Kruczek S, Biela A, Andrysiak K, Stępniewski J, Mikulski M, Gałęzowski M, Sitarz K, Brzózka K, Józkowicz A, Dulak J, Łoboda A. Synthetically Lethal Interactions of Heme Oxygenase-1 and Fumarate Hydratase Genes. Biomolecules. 2020 Jan 16;10(1):143.
[6] Costa D L, Namasivayam S, Amaral E P, et al. Pharmacological inhibition of host heme oxygenase-1 suppresses Mycobacterium tuberculosis infection in vivo by a mechanism dependent on T lymphocytes[J]. MBio, 2016, 7(5): 10.1128/mbio. 01675-16.

Tin protoporphyrin IX dichloride（SnPPIX）是一种合成血红素类似物，可选择性抑制血红素氧合酶1（HO-1）的活性（K_i = 11 nM），而不是HO-2（IC₅₀ = 7.5 μM）^[1-2]。Tin protoporphyrin IX dichloride可以微弱抑制内皮一氧化氮合酶和可溶性鸟苷酸环化酶的活性，IC₅₀值分别为35和30 μM^[2]。Tin protoporphyrin IX dichloride通常用于研究HO-1在细胞和动物中的作用。

Tin protoporphyrin IX dichloride（0.5,1,5,10和25 µM）处理293T细胞6小时即可抑制细胞中HO-1活性，但Tin protoporphyrin IX dichloride也可上调HO-1 mRNA和蛋白质水平^[3]。Tin protoporphyrin IX dichloride（10 µM）可以在小鼠成纤维细胞中抑制HO-1活性，诱导HO-1蛋白表达^[4]。此外，在UOK 262细胞中，10 µM Tin protoporphyrin IX dichloride可明显增加HMOX1 mRNA水平^[5]。

使用气溶胶结核分枝杆菌感染小鼠，并在同一天使用Tin protoporphyrin IX dichloride治疗（5 mg/kg），第六周时，Tin protoporphyrin IX dichloride处理明显减少小鼠肺部细菌负荷。在感染第四周开始使用Tin protoporphyrin IX dichloride治疗也出现了类似的效果^[6]。