| Bioactivity | SM 16 is a ALK5/ALK4 kinase inhibitor with Kis of 10 and 1.5 nM, respectively. | ||||||||||||
| Target | Ki: ALK5 (10 nM), ALK4 (1.5 nM) | ||||||||||||
| Invitro | 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]. | ||||||||||||
| In Vivo | 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]. | ||||||||||||
| Name | SM 16 | ||||||||||||
| CAS | 614749-78-9 | ||||||||||||
| Formula | C25H26N4O3 | ||||||||||||
| Molar Mass | 430.50 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| 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- [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. |