8,8'-[carbonylbis[imino-3,1-phenylenecarbonylimino(4-methyl-3,1-phenylene)carbonylimino]]bisnaphthalene-1,3,5-trisulphonic acid

Suramin is a reversible and competitive protein-tyrosine phosphatases (PTPases) inhibitor[1]. Suramin is a potent inhibitor of sirtuins: SirT1 (IC50=297 nM), SirT2 (IC50=1.15 μM), and SirT5 (IC50=22 μM)[2]. Suramin is a competitive inhibitor of reverse transcriptase (DNA topoisomerase II: IC50=5 μM)[3][4]. Suramin is a potent SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibitor[5].Suramin efficiently inhibits IP5K and is an antiparasitic, anti-neoplastic and anti-angiogenic agent[6][7][8].

ChEBI: Suramin is a member of the class of phenylureas that is urea in which each of the amino groups has been substituted by a 3-({2-methyl-5-[(4,6,8-trisulfo-1-naphthyl)carbamoyl]phenyl}carbamoyl)phenyl group. An activator of both the rabbit skeletal muscle RyR1 and sheep cardiac RyR2 isoform ryanodine receptor channels, it has been used for the treatment of human African trypanosomiasis for over 100 years. It has a role as a ryanodine receptor agonist, a GABA-gated chloride channel antagonist, a GABA antagonist, an apoptosis inhibitor, an antineoplastic agent, an angiogenesis inhibitor, a purinergic receptor P2 antagonist, an EC 2.7.11.13 (protein kinase C) inhibitor, an antinematodal drug and a trypanocidal drug. It is a member of phenylureas, a secondary carboxamide and a naphthalenesulfonic acid. It is functionally related to a naphthalene-1,3,5-trisulfonic acid. It is a conjugate acid of a suramin(6-).

Moderately toxic by intravenousroute. Human systemic effects by intravenous route: eyeeffects. An experimental teratogen. Other experimentalreproductive effects. When heated to decomposition itemits very toxic fumes of SOx and NOx.

SIRT1: 297 nM (IC₅₀); SIRT2: 1.15 μM (IC₅₀); SIRT5: 22 μM (IC₅₀)

[1] Zhang YL, et al. Suramin is an active site-directed, reversible, and tight-binding inhibitor of protein-tyrosine phosphatases. J Biol Chem. 1998 May 15;273(20):12281-7. DOI:10.1074/jbc.273.20.12281
[2] Trapp J, et al. Structure-activity studies on suramin analogues as inhibitors of NAD+-dependent histone deacetylases (sirtuins). ChemMedChem. 2007 Oct;2(10):1419-31. DOI:10.1002/cmdc.200700003
[3] Schuetz A, et al. Structural basis of inhibition of the human NAD+-dependent deacetylase SIRT5 by suramin. Structure. 2007 Mar;15(3):377-89. DOI:10.1016/j.str.2007.02.002
[4] De Clercq E, et al. Suramin: a potent inhibitor of the reverse transcriptase of RNA tumor viruses. Cancer Lett. 1979 Nov;8(1):9-22. DOI:10.1016/0304-3835(79)90017-x
[5] Wanchao Yin, et al. Structural basis for inhibition of the SARS-CoV-2 RNA polymerase by suramin. Nat Struct Mol Biol. 2021 Mar;28(3):319-325. DOI:10.1038/s41594-021-00570-0
[6] Jindal HK, et al. Suramin affects DNA synthesis in HeLa cells by inhibition of DNA polymerases. Cancer Res. 1990 Dec 15;50(24):7754-7. PMID:2174730
[7] Novaes RD, et al. Purinergic Antagonist Suramin Aggravates Myocarditis and Increases Mortality by EnhancingParasitism, Inflammation, and Reactive Tissue Damage in Trypanosoma cruzi-Infected Mice. Oxid Med Cell Longev. 2018 Sep 30;2018:7385639. DOI:10.1155/2018/7385639
[8] Izikki M, et al. The beneficial effect of suramin on monocrotaline-induced pulmonary hypertension in rats. PLoS One. 2013 Oct 15;8(10):e77073. DOI:10.1371/journal.pone.0077073
[9] Xiaozhe Zhang, et al. Suramin and NF449 Are IP5K Inhibitors That Disrupt IP6-mediated Regulation of Cullin RING Ligase and Sensitize Cancer Cells to MLN4924/pevonedistat. J Biol Chem. 2020 Jun 3;jbc.RA120.014375. DOI:10.1074/jbc.RA120.014375