For research use only. Not for therapeutic Use.
SM 16 is a ALK5/ALK4 kinase inhibitor with Kis of 10 and 1.5 nM, respectively.
SM 16 inhibits TGFβ-induced plasminogen activator inhibitor-luciferase activity (IC50=64 nM) and TGFβ- or activin-induced Smad2 phosphorylation at concentrations between 100 and 620 nM. SM 16 is tested against >60 related and unrelated kinases and shows moderate off-target activity only against Raf (IC50=1 μM) and p38/SAPKa (IC50=0.8 μM). SM 16 exhibits no inhibitory activity against ALK family members ALK1 and ALK6[1].
SM 16 penetrates tumor cells in vivo, suppressing tumor phosphorylated Smad2/3 levels for at least 3 h following treatment of tumor-bearing mice with a single i.p. bolus of 20 mg/kg SM 16. The growth of established AB12 tumors is significantly inhibited by 5 mg/kg/d SM 16 (P<0.001) delivered via s.c. miniosmotic pumps over 28 days[1].
| Catalog Number | I014681 |
| CAS Number | 614749-78-9 |
| Synonyms | 4-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl]bicyclo[2.2.2]octane-1-carboxamide |
| Molecular Formula | C25H26N4O3 |
| Purity | ≥95% |
| InChI | 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) |
| InChIKey | JUHTXZGCTPDXRU-UHFFFAOYSA-N |
| SMILES | CC1=NC(=CC=C1)C2=C(N=C(N2)C34CCC(CC3)(CC4)C(=O)N)C5=CC6=C(C=C5)OCO6 |
| Reference | [1]. Suzuki E, et al. 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]. Fu K, et al. 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]. Engebretsen KV, et al. 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. |
