SM16 is a novel and potent Type I TGF-β signaling inhibitor, also a ALK5/ALK4 kinase inhibitor with Kis of 10 and 1.5 nM, respectively.
Physicochemical Properties
| Molecular Formula | C25H26N4O3 |
| Molecular Weight | 430.498945713043 |
| Exact Mass | 430.2 |
| CAS # | 614749-78-9 |
| Related CAS # | 614749-78-9 |
| PubChem CID | 10387982 |
| Appearance | White to off-white solid powder |
| LogP | 3.1 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 32 |
| Complexity | 707 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O=C(C12CCC(C3=NC(C4=CC=C5C(=C4)OCO5)=C(C4C=CC=C(C)N=4)N3)(CC1)CC2)N |
| InChi Key | JUHTXZGCTPDXRU-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C25H26N4O3/c1-15-3-2-4-17(27-15)21-20(16-5-6-18-19(13-16)32-14-31-18)28-23(29-21)25-10-7-24(8-11-25,9-12-25)22(26)30/h2-6,13H,7-12,14H2,1H3,(H2,26,30)(H,28,29) |
| Chemical Name | 4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl]bicyclo[2.2.2]octane-1-carboxamide |
| 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 |
| 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 | At doses ranging from 100 to 620 nM, SM 16 suppresses both TGFβ- and activin-induced Smad2 phosphorylation as well as TGFβ-induced plasminogen activator dye luciferase activity (IC50=64 nM). Only SM 16 was tested against p38/SAPKa (IC50=0.8 μM) and Raf (IC50=1 μM) out of over 60 relevant and relevant factors. ALK1 and ALK6, members of the ALK family, are not inhibited by SM 16 [1]. |
| ln Vivo | A single intraperitoneal bolus dose of 20 mg/kg SM 16 decreases tumor phosphorylated Smad2/3 levels within tumor cells for a minimum of three hours following treatment of tumor-bearing cells. Subcutaneous microosmotic pump solution 5 mg/kg/d SM 16 (P<0.001) at 28 seconds substantially reduced established AB12 tumors [1]. |
| References |
[1]. A novel small-molecule inhibitor of transforming growth factor beta type I receptor kinase (SM16) inhibits murine mesothelioma tumor growth in vivo and prevents tumor recurrence after surgical resection. Cancer Res. 2007 Mar 1;67(5):2351-9. [2]. SM16, an orally active TGF-beta type I receptor inhibitor prevents myofibroblast induction and vascular fibrosis in the rat carotid injury model. Arterioscler Thromb Vasc Biol. 2008 Apr;28(4):665-71. [3]. Attenuated development of cardiac fibrosis in left ventricular pressure overload by SM16, an orally active inhibitor of ALK5. J Mol Cell Cardiol. 2014 Nov;76:148-57. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~65 mg/mL (~150.99 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.58 mg/mL (5.99 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 25.8 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: ≥ 2.58 mg/mL (5.99 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 25.8 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: ≥ 2.58 mg/mL (5.99 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 25.8 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 | 2.3229 mL | 11.6144 mL | 23.2288 mL | |
| 5 mM | 0.4646 mL | 2.3229 mL | 4.6458 mL | |
| 10 mM | 0.2323 mL | 1.1614 mL | 2.3229 mL |