Heptamidine dimethanesulfonate (SBi4211 dimethanesulfonate) is a highly potent Pentamidine-related inhibitor of the calcium-binding protein S100B (Kd=6.9 μM), specificly kills melanoma cells with S100B over those without S100B. Heptamidine is a useful tool for the investigation of Myotonic dystrophy (DM).
Physicochemical Properties
| Molecular Formula | C23H36N4O8S2 |
| Molecular Weight | 560.683943748474 |
| Exact Mass | 560.197 |
| CAS # | 161374-55-6 |
| Related CAS # | Heptamidine;94345-47-8 |
| PubChem CID | 146047121 |
| Appearance | Off-white to light yellow solid powder |
| Hydrogen Bond Donor Count | 6 |
| Hydrogen Bond Acceptor Count | 10 |
| Rotatable Bond Count | 12 |
| Heavy Atom Count | 37 |
| Complexity | 494 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | VJPVVWMWVOBCIC-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C21H28N4O2.2CH4O3S/c22-20(23)16-6-10-18(11-7-16)26-14-4-2-1-3-5-15-27-19-12-8-17(9-13-19)21(24)25;2*1-5(2,3)4/h6-13H,1-5,14-15H2,(H3,22,23)(H3,24,25);2*1H3,(H,2,3,4) |
| Chemical Name | 4-[7-(4-carbamimidoylphenoxy)heptoxy]benzenecarboximidamide;methanesulfonic acid |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | Heptamidine is an S100B-pentamidine complex. In every S100B monomer, two pentamidine molecules are combined. It is an S100B inhibitor [1]. HeLa cells expressing 960 CUG repeats show cytotoxicity at concentrations greater than 17.5 μM for heptamidine (20 μM), which does not significantly lower CUG levels in comparison to propamidine and pentamidine [2]. With an EC50 value of 15 μM, heptemidine can correct the mis-splicing of tiny gene reporter genes in the HeLa cell DM1 model [2]. |
| ln Vivo | In HSALR mice, heptamidine (ip; 20 or 30 mg/kg; 7 days) reduced exon 7a inclusions in a dose-dependent manner, with wild-type levels being reached at the 20 mg/kg dose (6±1%). Similarly, at doses of 20 or 30 mg/kg, myotonia decreased from grade 3 to grade 1 (sporadic myotonic discharges) or grade 0 [2]. |
| Animal Protocol |
Animal/Disease Models: Line 20b homozygous HSALR transgenic mice (FVB inbred background) with myotonic dystrophy (DM) mouse model [2] Doses: 20 or 30 mg/kg Route of Administration: intraperitoneal (ip) injection; Injection. 7 days; one time/day Experimental Results: Reversal of splicing defects and rescue of myotonia in mouse model of DM. |
| References |
[1]. 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]. Reducing levels of toxic RNA with small molecules.ACS Chem Biol. 2013 Nov 15;8(11):2528-37. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~62.5 mg/mL (~111.47 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.71 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.71 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (3.71 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7835 mL | 8.9177 mL | 17.8355 mL | |
| 5 mM | 0.3567 mL | 1.7835 mL | 3.5671 mL | |
| 10 mM | 0.1784 mL | 0.8918 mL | 1.7835 mL |