Heptamidine (SBi4211) is a potent Pentamidine-related inhibitor of the calcium-binding protein S100B (Kd=6.9 μM), selectively kills melanoma cells with S100B over those without S100B[1]. Heptamidine is a useful tool for the investigation of Myotonic dystrophy (DM)[2].
Heptamidine is a Pentamidine-S100B complex, two molecules of pentamidine bind per monomer of S100B, which performs to be an inhibitor for S100B[1].Heptamidine (20 μM) does not decrease CUG levels significantly when compares to Propamidine and Pentamidine, and exhibits cytotoxic at concentrations above 17.5 μM in HeLa cells expressing 960 CUG repeats[2].Heptamidine rescues mis-splicing of minigene reporters in a HeLa cell DM1 model with an EC50 value of 15 μM[2].
Heptamidine (intraperitoneal injection; 20 or 30 mg/kg; 7 days) causes a dose-dependent reduction of exon 7a inclusion in HSALR mice, returning to wild type levels (6±1%) when at 20 mg/kg dose, the myotonia is reduced from grade 3 to grade 1 (occasional myotonic discharge) or grade 0 at both 20 or 30 mg/kg[2]. Animal Model: Homozygous HSALR transgenic mice in line 20b (FVB inbred background) with a Myotonic dystrophy (DM) mouse model[2]
[1]. McKnight LE, et al. Structure-Based Discovery of a Novel Pentamidine-Related Inhibitor of the Calcium-Binding Protein S100B. ACS Med Chem Lett. 2012 Dec 13;3(12):975-979. Epub 2012 Sep 25. [2]. Coonrod LA, et al. Reducing levels of toxic RNA with small molecules.ACS Chem Biol. 2013 Nov 15;8(11):2528-37.