| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
| Targets |
KY-02327 targets the protein-protein interaction between Dishevelled (Dvl) and CXXC5. Dvl is a key intracellular signaling molecule in the Wnt/β-catenin pathway. CXXC5 is a negative regulator of this pathway that binds to Dvl and inhibits its function. By inhibiting the Dvl-CXXC5 interaction, KY-02327 disrupts this negative regulatory mechanism, thereby activating the Wnt/β-catenin pathway. This leads to the stabilization and nuclear accumulation of β-catenin, which drives the transcription of genes involved in osteoblast differentiation and bone formation.
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| ln Vitro |
Together with Runx2, KY-02327 (1–10 μM; 2 days; MC3T3E1 cells, a mouse preosteoblast cell line) elevates β-catenin protein levels and dose-dependently accumulates nuclear β-catenin [1]. The osteoblast development markers collagen 1a (Col1a) and osteocalcin (OCN) have their mRNA levels increased by KY-02327 (1-10 μM) [1].
In vitro, KY-02327 demonstrates potent activity in promoting osteoblast differentiation. In MC3T3E1 cells, a mouse pre-osteoblast cell line, treatment with KY-02327 (1-10 μM for 2 days) increases β-catenin protein levels and promotes nuclear β-catenin accumulation in a dose-dependent manner, working in conjunction with Runx2. It also increases the mRNA levels of osteoblast differentiation markers, including collagen 1a (Col1a) and osteocalcin (OCN). These results confirm its ability to activate the Wnt/β-catenin pathway and promote osteogenesis in vitro. |
| ln Vivo |
KY-02327 (20 mg/kg; oral; 5 days per week for 4 weeks) successfully recovered bone loss in an ovariectomized (OVX) mice model [1].
In vivo, KY-02327 has demonstrated efficacy in a mouse model of osteoporosis. In ovariectomized (OVX) mice, a model of postmenopausal osteoporosis, oral administration of KY-02327 (20 mg/kg, 5 days per week for 4 weeks) successfully rescued bone mineral density (BMD), bone volume, and trabecular bone structures. Calcein-labeled newly formed bone was diminished in the femurs of vehicle-treated OVX mice, while KY-02327 treatment restored bone formation. These findings support its potential as an anti-osteoporotic agent. |
| Enzyme Assay |
The inhibitory activity of KY-02327 against the Dvl-CXXC5 interaction is typically assessed using biochemical assays such as surface plasmon resonance (SPR) or AlphaScreen. These assays measure the disruption of the protein-protein interaction in the presence of varying concentrations of the compound. Its ability to activate the Wnt/β-catenin pathway is confirmed using cell-based reporter assays, such as the TOPFlash luciferase reporter, which measures β-catenin-mediated transcriptional activity.
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| Cell Assay |
The cellular activity of KY-02327 is evaluated in osteoblast precursor cell lines, such as MC3T3E1 mouse pre-osteoblasts. Cells are treated with varying concentrations of KY-02327, and the activation of the Wnt/β-catenin pathway is assessed by measuring β-catenin protein levels and nuclear localization by Western blot and immunofluorescence. The expression of osteoblast differentiation markers, including Runx2, Col1a, and OCN, is measured by qRT-PCR. These assays confirm the compound's ability to promote osteoblast differentiation.
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| Animal Protocol |
Animal/Disease Models: 8weeks old female BL6 mice (ovariectomy (OVX)-induced osteoporosis model mice) [1]
Doses: 20 mg/kg Route of Administration: Po; administered 5 days a week for 4 days Experimental Results: Newly formed bone labeled with calcein was diminished in the femurs of vehicle-treated OVX mice. In animal studies, KY-02327 is typically administered orally to rodents. In the OVX mouse model of osteoporosis, it was given at 20 mg/kg, 5 days per week for 4 weeks. Efficacy endpoints include the assessment of bone mineral density (BMD) by micro-CT, bone volume, and trabecular bone structures. Histomorphometric analysis of bone sections can also be performed to evaluate bone formation and resorption. |
| ADME/Pharmacokinetics |
KY-02327 has a molecular weight of 373.45 and a formula of C20H27N3O4. It is soluble in DMSO (100 mg/mL) and is typically stored as a powder at -20°C or in solution at -80°C. Its chemical name is ethyl 5-hydroxy-1-({[2-(piperidin-1-yl)ethyl]carbamoyl}methyl)-1H-indole-2-carboxylate. It has a LogP of 2.5 and a tPSA of 83.8. Detailed pharmacokinetic parameters are available from preclinical studies.
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| Toxicity/Toxicokinetics |
Toxicology data for KY-02327 is limited, as it is a research compound. Its safety profile has not been established in formal toxicology studies. However, its use in animal models at efficacious doses (20 mg/kg) suggests it is tolerated in those contexts. Its use is limited to research applications and it is not intended for human therapeutic use without further development.
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| References | |
| Additional Infomation |
KY-02327 (CAS: 2093407-25-9) is a valuable research tool for studying the Wnt/β-catenin signaling pathway and its role in bone biology. By inhibiting the Dvl-CXXC5 interaction, it provides a novel mechanism for activating Wnt signaling and promoting osteogenesis. Its efficacy in an OVX mouse model of osteoporosis highlights its potential as a therapeutic agent for bone loss disorders. It is a key compound for validating the Dvl-CXXC5 interaction as a therapeutic target for osteoporosis and other bone-related diseases.
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| Molecular Formula |
C20H27N3O4
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|---|---|
| Molecular Weight |
373.453
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| Exact Mass |
373.2
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| CAS # |
2093407-25-9
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| Related CAS # |
KY-02327 acetate
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| PubChem CID |
142737047
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| Appearance |
White to off-white solid powder
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| LogP |
2.5
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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 |
8
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| Heavy Atom Count |
27
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| Complexity |
510
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(CN1C(C(=O)OCC)=CC2C=C(C=CC1=2)O)NCCN1CCCCC1
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| InChi Key |
NJRAXCQBMGIWEE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H27N3O4/c1-2-27-20(26)18-13-15-12-16(24)6-7-17(15)23(18)14-19(25)21-8-11-22-9-4-3-5-10-22/h6-7,12-13,24H,2-5,8-11,14H2,1H3,(H,21,25)
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| Chemical Name |
ethyl 5-hydroxy-1-[2-oxo-2-(2-piperidin-1-ylethylamino)ethyl]indole-2-carboxylate
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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 (~267.77 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4.24 mg/mL (11.35 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 42.4 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 (6.69 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 25.0 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 (6.69 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 | 2.6777 mL | 13.3887 mL | 26.7773 mL | |
| 5 mM | 0.5355 mL | 2.6777 mL | 5.3555 mL | |
| 10 mM | 0.2678 mL | 1.3389 mL | 2.6777 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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