| Size | Price | Stock | Qty |
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| 10mg |
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| Targets |
p-STAT3
OSM-SMI-10B specifically targets the proinflammatory cytokine Oncostatin M (OSM) by binding directly to the protein. Computational docking studies have predicted its binding at Site III of OSM, a groove that is part of the OSM/OSMR (OSM receptor) interface. By binding OSM, it functions as a protein-protein interaction (PPI) inhibitor, physically blocking the cytokine from engaging its cognate receptor complex (OSMR and gp130). Consequently, this prevents the downstream activation of the JAK/STAT3 signaling pathway. OSM is an interleukin-6 family cytokine implicated in inflammation, tumor progression, and metastasis. This compound is the first reported small-molecule inhibitor targeting OSM directly. |
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| ln Vitro |
In cell-free assays, OSM-SMI-10B binds directly to Oncostatin M (OSM) with a dissociation constant (Kd) of 12.9-13.6 microM, demonstrating low-micromolar affinity. The more potent analog, SMI-10B13, exhibits a Kd of 6.6 microM. In cellular models, OSM-SMI-10B significantly reduces OSM-induced STAT3 phosphorylation (pSTAT3) in breast cancer cells (T47D and MCF-7) when co-incubated with OSM. The advanced analog SMI-10B13 shows strong inhibition, with IC50 values of 136 nM and 164 nM, respectively, while also inhibiting OSM-induced migration and invasion of cancer cells. It exhibits no significant cytotoxicity against non-cancerous mammary epithelial cells (MCF-10A).
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| ln Vivo |
The in vivo efficacy of the more potent analog SMI-10B13 has been demonstrated in mouse models of human breast cancer. In orthotopic xenografts using T47D cells, treatment with SMI-10B13 (10 mg/kg, i.p. injection on a Q.D. x 21 schedule) significantly reduced tumor volume (p < 0.001) over 21 days, showing superior tumor growth inhibition compared to vehicle control. Kaplan-Meier survival analysis revealed that SMI-10B13-treated mice had significantly prolonged survival compared to controls (p = 0.04). The primary compound OSM-SMI-10B serves as a research tool, but this related compound demonstrates the potential of the OSM inhibitor class to be developed into an effective anti-cancer therapeutic.
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| Enzyme Assay |
Binding studies employ multiple biophysical techniques to characterize the SMI/OSM interaction. A fluorescence quenching assay is used to measure the binding affinity (Kd) of the compound. Surface Plasmon Resonance (SPR) can be performed by immobilizing recombinant OSM protein on a sensor chip and flowing various concentrations of OSM-SMI-10B to determine the kinetic binding parameters (ka, kd, Kd). Additionally, NMR spectroscopy can be used; a ¹H-¹⁵N HSQC titration of ¹⁵N-labeled OSM with increasing concentrations of the compound causes chemical shift perturbations (CSPs), allowing identification of the binding site (predicted to be Site III) and determination of the Kd from the CSP curves.
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| Cell Assay |
For pSTAT3 inhibition assays, T47D or MCF-7 human breast cancer cells are cultured in RPMI-1640 medium. Cells are seeded (e.g., 5×10⁵ cells/well) in serum-free media overnight. They are pre-treated with varying concentrations of OSM-SMI-10B (0-100 microM) for 1 hour, followed by stimulation with recombinant human Oncostatin M (OSM, e.g., 20 ng/mL) for 15 minutes. The cells are then lysed, and the level of phosphorylated STAT3 (Tyr705) and total STAT3 are quantified by a sandwich ELISA kit, or detected by Western blotting with specific antibodies. For migration assays, T47D cells are treated with SMI-10B13 in the presence or absence of OSM in a Boyden chamber for 24 hours. Cells that migrated through the membrane are stained and quantified. In vitro cytotoxicity is assessed using a 3-day MTT assay.
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| Animal Protocol |
An orthotopic human breast cancer xenograft model is established using female NOD/SCID mice (6-8 weeks, n=10/group). Mice are injected orthotopically with 1×10⁶ T47D or MCF-7 cells suspended in 50% Matrigel. When tumors reach an average size of ~100 mm3 (approx. 21 days), the more potent analog SMI-10B13 is administered via intraperitoneal (i.p.) injection. A typical dosing regimen is 10 mg/kg administered once daily (Q.D. x 21). Control groups receive either vehicle only (e.g., 10% DMSO, 10% Cremophor EL, 80% saline) or a non-targeting control. Tumor volumes are measured twice weekly with calipers. Body weight is monitored for signs of toxicity. At the study endpoint, tumors are excised, weighed, and processed for immunohistochemistry (Ki-67, pSTAT3, cleaved caspase-3) and Western blotting to confirm target engagement.
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| ADME/Pharmacokinetics |
OSM-SMI-10B has a molecular weight of 378.33 g/mol. The solid is stored at -20degC (up to 3 years) or 4degC (up to 2 years). For in vitro use, a stock solution can be prepared in DMSO to a concentration of 250 mg/mL (660.80 mM). For in vivo administration of its analog, a formulation protocol is as follows: dissolve in 10% DMSO, then add 40% PEG300, then 5% Tween-80, and finally 45% saline to reach a final concentration of ≥ 6.25 mg/mL (16.52 mM). The diluted solution should be administered immediately. OSM-SMI-10B is a first-in-class small-molecule inhibitor (SMI) directly targeting oncostatin M (OSM). It is a tetrasubstituted furan derivative. The compound is for research use only.
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| Toxicity/Toxicokinetics |
This research-grade compound is not for human use. No specific toxicity data for OSM-SMI-10B is available, but in vivo studies with the more potent analog SMI-10B13 in mice at 10 mg/kg for 21 days did not report significant body weight loss or signs of gross toxicity. The primary risks are related to the DMSO vehicle. OSM-SMI-10B is a pSTAT3 inhibitor. It is used in JAK/STAT signaling research for cancer and inflammation/immunology. As a chemical probe, it should be handled using standard laboratory safety practices, including the use of personal protective equipment. This compound is not an FDA-approved drug.
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| References | |
| Additional Infomation |
OSM-SMI-10B is a first-in-class small-molecule inhibitor targeting Oncostatin M (OSM), a proinflammatory cytokine implicated in inflammatory diseases and multiple cancers, especially breast cancer. The compound inhibits the OSM/OSMR protein-protein interaction (PPI), which leads to a reduction in OSM-induced STAT3 phosphorylation. The more potent analog SMI-10B13 has been shown to reduce tumor growth and improve survival in mouse models of human breast cancer. OSM is an IL-6 family cytokine that promotes breast tumor cell detachment, invasion, metastasis, and the expression of tumorigenic proteins. This research demonstrates the potential of direct-acting OSM inhibitors as a therapeutic strategy. The compound is a part of the JAK/STAT signaling pathway. The CAS number for OSM-SMI-10B is 2502294-55-3.
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| Molecular Formula |
C21H14O7
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| Molecular Weight |
378.33
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| Exact Mass |
378.074
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| Related CAS # |
2502294-55-3
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| PubChem CID |
155202044
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
28
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| Complexity |
608
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1OC2=C(O1)C=C(C=C2)C3=C(OC(=C3)/C=C/C(=O)O)C4=CC5=C(C=C4)OCO5
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| InChi Key |
KCTZPNCRBRJVBH-ZZXKWVIFSA-N
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| InChi Code |
InChI=1S/C21H14O7/c22-20(23)6-3-14-9-15(12-1-4-16-18(7-12)26-10-24-16)21(28-14)13-2-5-17-19(8-13)27-11-25-17/h1-9H,10-11H2,(H,22,23)/b6-3+
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| Chemical Name |
(E)-3-[4,5-bis(1,3-benzodioxol-5-yl)furan-2-yl]prop-2-enoic acid
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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 :~250 mg/mL (~660.80 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (16.52 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 62.5 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: ≥ 6.25 mg/mL (16.52 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 62.5 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6432 mL | 13.2160 mL | 26.4320 mL | |
| 5 mM | 0.5286 mL | 2.6432 mL | 5.2864 mL | |
| 10 mM | 0.2643 mL | 1.3216 mL | 2.6432 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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