| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 1g | |||
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| Targets |
Smurf1 modulator-1 targets Smad ubiquitination regulatory factor 1 (Smurf1), an E3 ubiquitin ligase that recognizes and ubiquitinates Smad proteins and other substrates. Smurf1 plays critical roles in the degradation of components of the BMP and TGF-beta signaling pathways. By inhibiting Smurf1, this modulator stabilizes its substrates, thereby enhancing BMP signaling and promoting osteoblast differentiation while inhibiting TGF-beta-induced fibrosis.
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| ln Vitro |
Smurf1 modulator-1 is a selective inhibitor of Smurf1 with an IC50 of 180 nM in biochemical assays. It demonstrates no significant inhibition against other related E3 ligases such as Smurf2 or Nedd4 at comparable concentrations, indicating selectivity. The compound enhances BMP signaling in cellular models and promotes osteogenic differentiation. No specific cytotoxicity data are reported at the active concentration range.
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| ln Vivo |
No specific in vivo activity data for Smurf1 modulator-1 are reported in the search results. As a selective Smurf1 inhibitor, it has potential for evaluation in animal models of bone regeneration (e.g., calvarial defect models, fracture healing), fibrosis (e.g., bleomycin-induced pulmonary fibrosis), and cancer. The compound could be administered systemically (oral or intraperitoneal) to assess effects on bone formation or anti-fibrotic activity. No dosing information is available.
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| Enzyme Assay |
Binding of Smurf1 modulator-1 to Smurf1 is measured by standard in vitro ubiquitination or biochemical inhibition assays using purified recombinant Smurf1 enzyme. The compound is incubated with Smurf1, a substrate (e.g., Smad1 or a ubiquitination reporter), ubiquitin, and E1 and E2 enzymes. The reaction is allowed to proceed, and the extent of ubiquitination is detected by Western blot using anti-ubiquitin antibodies or by measuring fluorescence if a labeled substrate is used. The IC50 value of 180 nM is calculated from dose-response curves.
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| Cell Assay |
For cellular assays, cells expressing Smurf1 and its substrates (e.g., C2C12 myoblasts for BMP signaling, or A549 lung epithelial cells for TGF-beta signaling) are seeded in 6- or 96-well plates. Cells are treated with Smurf1 modulator-1 at graded concentrations (0.01-100 microM) for 6-24 hours. For BMP signaling, cells are then stimulated with BMP-2 or BMP-4 for 24-48 hours. Smad1/5/9 phosphorylation and total Smad1 levels are measured by Western blot. Osteoblast differentiation is assessed by alkaline phosphatase (ALP) activity, Alizarin Red S staining for mineralization, and expression of osteogenic markers (Runx2, Osterix, ALP) by qPCR. For TGF-beta signaling, Smad2/3 phosphorylation and fibrotic marker expression (collagen I, alpha-SMA) are assessed.
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| Animal Protocol |
No animal experiments for Smurf1 modulator-1 are described in the search results. For in vivo evaluation of bone regeneration, 6-8-week-old male C57BL/6 mice would be used in a calvarial defect model, where a 5-mm critical-sized defect is created in the parietal bone. Smurf1 modulator-1 would be administered locally (via a collagen scaffold or hydrogel) at doses of 0.1-10 microg/defect, or systemically (oral or IP, 10-50 mg/kg) daily for 2-4 weeks. Bone regeneration would be assessed by micro-CT, histology (H&E, Masson‘s trichrome, and ALP staining), and biomechanical testing. For fibrosis models, bleomycin-induced lung fibrosis in mice would be treated with the compound, and collagen deposition and inflammatory markers would be assessed.
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| ADME/Pharmacokinetics |
Smurf1 modulator-1 (C23H34N4O₅, MW = 446.54, purity ≥99.76%, CAS 1825371-51-4) is a white to off-white solid powder. For storage, the powder should be kept at -20degC for up to 3 years, sealed, and protected from light. For in vitro use, stock solutions in DMSO (125 mg/mL, 279.93 mM) can be stored at -80degC for up to 6 months or at -20degC for 1 month. For in vivo use, it can be formulated in 10% DMSO / 40% PEG300 / 5% Tween-80 / 45% saline. No detailed PK parameters are reported.
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| Toxicity/Toxicokinetics |
No specific toxicity data for Smurf1 modulator-1 are reported in the search results. The compound is noted to have low cytotoxicity in cellular assays, suggesting a favorable safety profile. As a research-grade inhibitor, it is not intended for human or veterinary use. Standard laboratory safety precautions for handling chemicals should be followed, including the use of gloves, lab coat, and safety goggles. No LD50 or formal toxicology studies are available.
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| References | |
| Additional Infomation |
Smurf1 modulator-1 (Compound 20) is a research-grade selective inhibitor of Smurf1, an E3 ubiquitin ligase that regulates BMP and TGF-beta signaling. Smurf1 plays key roles in bone formation (by degrading Smad1/5, the mediators of BMP signaling), fibrosis (by degrading Smad7, an inhibitor of TGF-beta signaling), and cancer (by degrading tumor suppressors). Inhibitors of Smurf1 are of interest for promoting bone regeneration, treating fibrosis, and as potential anticancer agents. The compound is for research use only and has not entered clinical trials or received regulatory approval. It was reported in a patent (WO2015175796).
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| Molecular Formula |
C23H34N4O5
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| Molecular Weight |
446.54
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| Exact Mass |
446.252
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| CAS # |
1825371-51-4
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| PubChem CID |
118511179
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| Appearance |
White to off-white solid powder
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| LogP |
2.8
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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 |
32
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| Complexity |
778
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O1[C@@H](C)[C@H](C2=C(C)C(C(NC3=C(C)N(C)N(C3=O)C3CCCCC3)=O)=NO2)OCC1(C)C
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| InChi Key |
LVDRKBFVIUBIBB-MGPUTAFESA-N
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| InChi Code |
InChI=1S/C23H34N4O5/c1-13-17(25-32-19(13)20-15(3)31-23(4,5)12-30-20)21(28)24-18-14(2)26(6)27(22(18)29)16-10-8-7-9-11-16/h15-16,20H,7-12H2,1-6H3,(H,24,28)/t15-,20+/m0/s1
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| Chemical Name |
N-(1-cyclohexyl-2,3-dimethyl-5-oxopyrazol-4-yl)-4-methyl-5-[(2R,3S)-3,5,5-trimethyl-1,4-dioxan-2-yl]-1,2-oxazole-3-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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2394 mL | 11.1972 mL | 22.3944 mL | |
| 5 mM | 0.4479 mL | 2.2394 mL | 4.4789 mL | |
| 10 mM | 0.2239 mL | 1.1197 mL | 2.2394 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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