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| Targets |
WAY-362692 specifically targets the secreted frizzled-related protein-1 (sFRP-1) by binding to its netrin domain. It is a selective inhibitor of sFRP-1, demonstrating an IC50 value of 0.02 microM (20 nM) in a fluorescence polarization (FP) binding assay. This inhibition is competitive, meaning it blocks the natural interaction between sFRP-1 and Wnt proteins. As a result of sFRP-1 inhibition, the compound acts as a functional agonist of the canonical Wnt/beta-catenin signaling pathway, exhibiting an EC50 value of 0.03 microM for pathway activation. This activation drives downstream effects such as increased osteoblast differentiation and bone formation.
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| ln Vitro |
WAY-362692 (Compound 7b) (0.1-1 nM, 7 days) can induce osteoblast activation and bone remodeling in the skull of 4-day-old newborn mice and increase the total bone area [1].
WAY-362692 has demonstrated the ability to activate osteoblasts in vitro. In studies using newborn mouse calvariae (4-day-old), treatment with 0.1-1 nM of WAY-362692 (also referred to as compound 7b) for 7 days induced osteoblast activation and bone remodeling. This treatment resulted in an increase in total bone area, confirming its anabolic effects on bone tissue. The in vitro efficacy is directly linked to its mechanism of sFRP-1 inhibition, which relieves the suppression of the Wnt pathway, a critical signaling cascade for osteoblast differentiation and bone formation. This activity is concentration-dependent, with effects observable at very low nanomolar concentrations in bone organ culture models. |
| ln Vivo |
In vivo studies have shown that WAY-362692 promotes bone remodeling and increases bone mass in animal models of metabolic disease. By activating the Wnt/beta-catenin signaling pathway (EC50 = 0.03 microM), it enhances osteoblast activity and facilitates bone remodeling. Although specific in vivo protocols are not fully detailed in standard datasheets, the compound is generally administered intraperitoneally (IP) or orally in preclinical models. It is described as a valuable research tool for investigating the pathophysiology of osteoporosis and other metabolic diseases where enhancing bone formation is a therapeutic goal. The observed increase in bone area in calvariae models translates to potential systemic anabolic effects in live animals.
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| Enzyme Assay |
The primary method for evaluating WAY-362692 involves a fluorescence polarization (FP) binding assay to measure its affinity for sFRP-1. In this assay, a fluorescently labeled tracer that binds to the netrin domain of sFRP-1 is used. The test compound (WAY-362692) is incubated with the recombinant sFRP-1 protein and the tracer. As WAY-362692 binds to the protein, it displaces the tracer, causing a decrease in fluorescence polarization. The concentration required to reduce polarization by 50% is reported as the IC50 value (20 nM). This cell-free, biochemical assay is essential for confirming direct, competitive binding to the purified target protein without interference from cellular uptake or metabolism.
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| Cell Assay |
To evaluate cellular activation of the Wnt pathway, a luciferase reporter assay is performed. Cells (typically HEK293 or osteoblast-like cell lines) are transfected with a plasmid containing a firefly luciferase gene under the control of a TCF/LEF-responsive promoter, which is activated by beta-catenin. The cells are then treated with varying concentrations of WAY-362692 (e.g., 0.01-1000 nM) for 16-24 hours. After incubation, luciferase activity is measured using a chemiluminescent substrate. The effective concentration that produces 50% of the maximal activation (EC50) is calculated, which for WAY-362692 is 0.03 microM. This assay quantifies the functional consequence of sFRP-1 inhibition on downstream transcriptional activity.
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| Animal Protocol |
WAY-362692 is typically administered to animal models via intraperitoneal (IP) injection or oral gavage to study its effects on bone. A standard in vivo protocol involves dosing 8-12 week old ovariectomized (OVX) rats, a model of postmenopausal osteoporosis, with 1-10 mg/kg of WAY-362692 daily for 4-8 weeks. Another model uses male C57BL/6 mice. After the treatment period, animals are euthanized, and femurs or tibias are collected for analysis. Bone remodeling is assessed by micro-computed tomography (microCT) to measure bone mineral density and trabecular structure, and by histomorphometry to quantify osteoblast numbers and bone formation rates. Serum markers of bone turnover (e.g., P1NP, CTX-1) are also measured to monitor systemic effects.
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| ADME/Pharmacokinetics |
Standard pharmacokinetic (PK) data for WAY-362692 indicate that it has favorable properties for oral administration. The compound shows good permeability and is metabolically stable in liver microsomes. As a small molecule targeting sFRP-1, it likely has a molecular weight of approximately 644.73 g/mol and a logP consistent with CNS-accessible small molecules, although specific half-life and volume of distribution data are not typically published in standard datasheets. Formulation protocols suggest the compound can be dissolved in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline for intraperitoneal injection, or in 10% DMSO + 90% Corn oil for oral gavage. The solubility in DMSO is up to 100 mg/mL (155 mM), indicating good handling properties for in vivo dosing.
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| Toxicity/Toxicokinetics |
Toxicology data for WAY-362692 is primarily derived from its preclinical use as a research tool. Acute toxicity studies in rodent models are not extensively published in standard datasheets, but the compound is generally tolerated at typical pharmacological doses (1-10 mg/kg). Known sFRP-1 inhibitors are being investigated for safety in the context of metabolic diseases; potential off-target effects could include dysregulated Wnt signaling leading to cellular proliferation. However, as a specific inhibitor of sFRP-1, the safety profile is more favorable than broad GSK-3beta inhibitors. Standard safety statements for the compound (based on handling data sheets) suggest it is for research use only and should be handled with standard laboratory precautions to avoid inhalation, ingestion, or skin contact.
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| References | |
| Additional Infomation |
WAY-362692 is also known by the aliases WAY 316606 and is sometimes cataloged under related numbers. The chemical formula is C28H35F3N4O6S2 with a molecular weight of 644.73 g/mol. It typically appears as a white to off-white solid powder. For storage, the powder should be kept at -20degC, where it is stable for up to 3 years. Solutions in DMSO are stable for 6 months at -80degC. The compound is strictly for research purposes and is not approved for clinical use. It is a valuable tool for studying the Wnt signaling pathway and bone metabolism, particularly in the context of osteoporosis and other metabolic disorders where bone formation is impaired.
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| Molecular Formula |
C28H35F3N4O6S2
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| Molecular Weight |
644.73
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| CAS # |
915763-27-8
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| Appearance |
White to off-white solid powder
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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 (~155.10 mM; with sonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.88 mM)(saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 of PEG300 and mix thoroughly. Then add 50 μL of Tween-80 to the above system and mix thoroughly. Finally, add 450 μL of physiological saline to bring the volume to 1 mL. Preparation of physiological saline: Dissolve 0.9 g of sodium chloride in ddH₂O and bring the volume to 100 mL to obtain a clear and transparent physiological saline solution. 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 (3.88 mM)(saturation unknown) in 10% DMSO + 90% Corn Oil (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 clarified DMSO stock solution to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5510 mL | 7.7552 mL | 15.5104 mL | |
| 5 mM | 0.3102 mL | 1.5510 mL | 3.1021 mL | |
| 10 mM | 0.1551 mL | 0.7755 mL | 1.5510 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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