| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
SM16 targets the transforming growth factor-β (TGF-β) type I receptor kinase, also known as ALK5 (activin receptor-like kinase 5). By inhibiting ALK5, SM16 blocks the phosphorylation of SMAD2/3, preventing their nuclear translocation and subsequent activation of TGF-β-responsive genes. This inhibits TGF-β signaling, which is involved in fibrosis, cancer progression, and immune regulation.
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| 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].
SM16 is a potent inhibitor of ALK5 with an IC50 of approximately 10 nM. It selectively inhibits ALK5 over other kinases. In cell-based assays, SM16 blocks TGF-β-induced SMAD2/3 phosphorylation and inhibits TGF-β-responsive gene expression. This demonstrates its potent and selective in vitro activity as a TGF-β signaling inhibitor. |
| 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].
SM16 has demonstrated in vivo activity in various disease models. In animal models of fibrosis, SM16 has been shown to reduce fibrosis and improve organ function. In cancer models, it has been shown to inhibit tumor growth and metastasis. These studies confirm its in vivo efficacy as a TGF-β signaling inhibitor. |
| Enzyme Assay |
The in vitro activity of SM16 is assessed using kinase inhibition assays with purified recombinant ALK5. The compound is incubated with the enzyme and a substrate, and the extent of inhibition is measured. The IC50 of approximately 10 nM is determined from these assays. Selectivity profiling against other kinases is performed to confirm specificity.
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| Cell Assay |
Cell-based assays are used to evaluate SM16's ability to inhibit TGF-β signaling. Cells are treated with TGF-β in the presence or absence of SM16. The phosphorylation of SMAD2/3 is measured by Western blot or ELISA. The expression of TGF-β-responsive genes, such as PAI-1 or collagen, can be measured by quantitative PCR.
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| Animal Protocol |
SM16 has been evaluated in animal models of fibrosis and cancer. In these studies, the compound is typically administered orally or intraperitoneally to disease models. Its effects on fibrosis, tumor growth, metastasis, and other disease endpoints are assessed. Biomarkers of TGF-β signaling, such as SMAD2/3 phosphorylation, can be measured in tissue samples.
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| ADME/Pharmacokinetics |
SM16 has a molecular weight of approximately 487.6 and a molecular formula of C28H34N6O2. Purity is typically ≥98%. The compound is soluble in DMSO. Storage is recommended at -20°C for long-term stability. SM16 is a potent and selective ALK5 inhibitor and is used as a research tool in fibrosis and cancer research.
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| Toxicity/Toxicokinetics |
SM16 is a research compound and its full toxicological profile is not detailed in the available literature. As a TGF-β signaling inhibitor, it could have effects on immune function, wound healing, and other processes regulated by TGF-β. Its safety profile would be evaluated in preclinical toxicology studies for its development as a therapeutic agent.
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| References |
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| Additional Infomation |
SM16 (CAS#: 614749-78-9) is a potent and selective inhibitor of the TGF-β type I receptor kinase (ALK5) with an IC50 of approximately 10 nM. It blocks TGF-β signaling by inhibiting ALK5-mediated SMAD2/3 phosphorylation. SM16 has demonstrated in vivo efficacy in models of fibrosis and cancer. It is a valuable research tool for studying TGF-β signaling in fibrosis, cancer, and other diseases.
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| Molecular Formula |
C25H26N4O3
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|---|---|
| Molecular Weight |
430.498945713043
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| Exact Mass |
430.2
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| CAS # |
614749-78-9
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| Related CAS # |
614749-78-9
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| PubChem CID |
10387982
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| Appearance |
White to off-white solid powder
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| LogP |
3.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
32
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| Complexity |
707
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C12CCC(C3=NC(C4=CC=C5C(=C4)OCO5)=C(C4C=CC=C(C)N=4)N3)(CC1)CC2)N
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| InChi Key |
JUHTXZGCTPDXRU-UHFFFAOYSA-N
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| 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)
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| 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
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~65 mg/mL (~150.99 mM)
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| 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. View More
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. |
| 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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