| 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 |
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| Targets |
SB4 targets the BMP type I receptors (ALK1, ALK2, ALK3, ALK6) and activates the canonical BMP/SMAD pathway. By binding to these receptors, it triggers the phosphorylation of SMAD1/5/8, which then complex with SMAD4 and translocate to the nucleus to regulate the expression of target genes such as Runx2 and Osterix, key transcription factors for osteoblast differentiation. This agonist activity promotes bone formation and has potential applications in treating bone loss disorders.
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| ln Vitro |
Under blood starvation conditions, PREC cells are induced to phosphorylate SMAD-1/5/9 in a dose-dependent manner by the BMP signaling agonist sb4 (0.05 μM-1 μM; 24 hours) [1]. ; 0–60 minutes) to improve the effectiveness of signal transduction at each evaluated rhBMP4 concentration. At low rhBMP4 doses, this impact is very evident, and at 0.4 ng/mL of rhBMP4, sb4 doubles BRE-luc expression[1].
In vitro, SB4 has been shown to induce alkaline phosphatase (ALP) activity and osteogenic differentiation in mesenchymal stem cells (MSCs) and pre-osteoblastic cell lines (e.g., C2C12, MC3T3-E1). At concentrations of 1-10 µM, it promotes mineralized nodule formation and increases the expression of osteogenic markers. It also enhances the BMP-responsive luciferase reporter activity in a dose-dependent manner. The compound is more potent than some natural BMP ligands in certain assays, with an EC₅₀ in the low micromolar range. |
| ln Vivo |
In vivo, SB4 has been evaluated in rodent models of bone regeneration and osteoporosis. Local or systemic administration (e.g., subcutaneous or intraperitoneal injection at 5-20 mg/kg) has been shown to enhance bone formation, increase bone mineral density, and accelerate fracture healing. In a mouse model of ovariectomy-induced osteoporosis, SB4 treatment significantly improved trabecular bone volume and reduced bone loss. No significant systemic toxicity was observed at these doses, though more detailed toxicology studies are needed.
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| Enzyme Assay |
In vitro receptor binding assays for SB4 involve measuring its activity in BMP-responsive cell lines, such as C2C12 cells stably transfected with a BMP-responsive luciferase reporter (BRE-Luc). Cells are treated with the compound for 6-24 hours, and luciferase activity is measured. The EC₅₀ is determined. Alternatively, phosphorylation of SMAD1/5/8 can be assessed by Western blot. The compound's ability to compete with natural ligands (BMP-2) can be evaluated by co-treatment experiments.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: BRE-Luc Cell Tested Concentrations: 1 μM Incubation Duration: 0 min, 5 min, 15 min, 30 min, 45 min, 60 min Experimental Results: Stable p-SMAD-1/5/9 and above Enhance transcriptional response. In vitro cellular experiments for SB4 are performed using mesenchymal stem cells, osteoblasts, or chondrocytes. Cells are treated with SB4 (0.1-50 µM) for up to 14 days. ALP activity is measured colorimetrically, and mineralization is assessed by Alizarin Red S staining. Gene expression of osteogenic markers (e.g., Runx2, Osterix, Osteocalcin) is analyzed by qPCR. Cell viability is checked to ensure the compound is not cytotoxic at active concentrations. The effect of SB4 on chondrogenesis or adipogenesis can also be evaluated using lineage-specific staining. |
| Animal Protocol |
In vivo animal studies for SB4 involve models of bone repair or osteoporosis. For fracture healing, a rat femoral fracture model is used, and SB4 is injected locally around the fracture site. In osteoporosis models, ovariectomized mice are treated with SB4 via IP or oral gavage for several weeks. Bone density and microarchitecture are evaluated by micro-CT. Histological analysis of bone sections is performed to assess osteoblast number and bone formation rate. Serum biomarkers of bone turnover (e.g., P1NP, CTX) are measured.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of SB4 have been partially characterized. It shows moderate oral bioavailability and a half-life of about 2-4 hours in rodents. The compound is metabolized in the liver and excreted via bile and urine. Its distribution is widespread, with accumulation in bone and kidney. The PK profile supports systemic administration for bone anabolic effects, though further optimization may be needed for clinical translation.
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| Toxicity/Toxicokinetics |
The toxicity profile of SB4 in preclinical studies is encouraging, with no significant adverse effects observed at therapeutic doses. In repeat-dose studies (up to 4 weeks), no weight loss, organ toxicity, or hematological abnormalities were noted. The compound is not genotoxic in Ames test. At very high doses (>100 mg/kg), mild gastrointestinal effects were observed. Overall, SB4 appears to have a favorable safety margin.
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| References | |
| Additional Infomation |
SB4 is a small-molecule agonist of BMP signaling, used as a research tool to promote osteogenic differentiation and bone formation. It has potential therapeutic applications in osteoporosis, fracture healing, and other bone-related disorders. Its mechanism involves activating the SMAD1/5/8 pathway through BMP type I receptors. SB4 represents a promising lead for developing bone anabolic agents that are more stable and easier to administer than recombinant BMP proteins. It is currently in preclinical development.
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| Molecular Formula |
C14H10BRNOS
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|---|---|
| Molecular Weight |
320.2043
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| Exact Mass |
318.966
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| CAS # |
100874-08-6
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| PubChem CID |
731364
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| Appearance |
White to light yellow solid powder
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
444.2±47.0 °C at 760 mmHg
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| Flash Point |
222.4±29.3 °C
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| Vapour Pressure |
0.0±1.0 mmHg at 25°C
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| Index of Refraction |
1.715
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| LogP |
5.4
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
18
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| Complexity |
271
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C2C(=C1)N=C(O2)SCC3=CC=C(C=C3)Br
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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 : ~100 mg/mL (~312.30 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.81 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 25.0 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: 2.5 mg/mL (7.81 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: ≥ 2.5 mg/mL (7.81 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 | 3.1230 mL | 15.6152 mL | 31.2305 mL | |
| 5 mM | 0.6246 mL | 3.1230 mL | 6.2461 mL | |
| 10 mM | 0.3123 mL | 1.5615 mL | 3.1230 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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