Y1693
Based on 1 Customer Validation
Y1693 is an orally active RANKL inhibitor with a Kd of 5.03 μM for hRANKL. Y1693 inhibits the activation of the downstream c-fos/NFATc1 signaling pathway by blocking its interaction with RANK. Y1693 significantly inhibits RANKL-induced osteoclast differentiation, F-actin ring formation and bone resorptive activity, while downregulating the mRNA and protein expressions of TRAP, cathepsin K, c-fos and NFATc1. Y1693 shows no obvious cytotoxicity to bone marrow-derived macrophages and osteoclast precursor cells, and exhibits favorable ADME properties. Y1693 improves ovariectomy-induced osteoporosis in mice and reverses ligation-induced periodontal alveolar bone loss. Y1693 is applicable to research related to osteoporosis and periodontal diseases.
For research use only. We do not sell to patients.
- Purity : 99.91%
- CAS No.: 2812381-74-9
- Formula: C28H25N3O
- Molecular Weight:419.52
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
All Cathepsin Isoforms
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Biological Activity
Description
IC50 & Target
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Cathepsin E |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| BMDM | IC50 |
0.52 μM
Compound: 1; Y1693
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Anti-osteoporosis activity C57/BL6 mouse bone marrow macrophage cells assessed as inhibition of RANKL-induced osteoclastogenesis measured after 5 to 6 days in presence of M-CSF by DAPI staining analysis
Anti-osteoporosis activity C57/BL6 mouse bone marrow macrophage cells assessed as inhibition of RANKL-induced osteoclastogenesis measured after 5 to 6 days in presence of M-CSF by DAPI staining analysis
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[PMID: 35960655] |
In Vitro
Y1693 (0.1-10 μM; 5-6 day) potently inhibits RANKL-induced osteoclastogenesis in BMMs with an IC50 of 0.52 μM, achieving 89.3% inhibition at 1 μM and 45.9% inhibition at 0.1 μM[1].
Y1693 (1-10 μM; 3 day) is non-cytotoxic to BMMs at concentrations up to 10 μM[1].
Y1693 (0.1-5 μM; 5-6 day) inhibits RANKL-induced F-actin ring formation in BMM-derived osteoclasts in vitro in a dose-dependent manner[1].
Y1693 (0.5-5 μM; 3 day) dose-dependently downregulates the mRNA expression of TRAP, cathepsin K, c-fos, and NFATc1 in RANKL-stimulated BMMs[1].
Y1693 (1-10 μM; 3 day) dose-dependently inhibits the protein expression of c-fos and NFATc1 in RANKL-stimulated BMMs[1].
Y1693 (0.1-5 μM; 2 day) dose-dependently inhibits RANKL-induced bone resorption by mature osteoclasts on bovine femur bone slices, with nearly complete inhibition at 5 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:bone marrow-derived macrophages (BMMs)
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Concentration:1 μM, 2.5 μM, 5 μM, 10 μM
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Incubation Time:3 day
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Result:Showed no cytotoxicity to BMMs at concentrations up to 10 μM.
Maintained relative cell viability above 1.5-fold (similar to untreated controls) across all tested concentrations.
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Cell Line:bone marrow-derived macrophages (BMMs)
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Concentration:0.5 μM, 1 μM, 2.5 μM, 5 μM
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Incubation Time:3 day
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Result:Dose-dependently reduced the RANKL-induced upregulation of osteoclast marker genes.
Suppressed TRAP, cathepsin K, c-fos, and NFATc1 mRNA levels to near basal (unstimulated) levels at 5 μM.
Exhibited significant inhibition at concentrations as low as 0.5 μM.
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Cell Line:bone marrow-derived macrophages (BMMs)
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Concentration:1 μM, 2.5 μM, 5 μM, 10 μM
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Incubation Time:3 day
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Result:Reduced the protein expression of c-fos and NFATc1 in a dose-dependent manner.
Showed decreasing protein levels as concentration increased from 1 μM to 10 μM.
Parmacokinetics
In Vivo
Y1693 (20 mg/kg; i.p.; daily; 28 days) increases alveolar bone mass by 60.7%, bone volume by 51.9%, while ameliorating ligature-induced periodontal bone loss in mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 mice with Osteoporosis (8-week-old female; ovariectomy-induced osteoporosis)[1]
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Dosage:20 mg/kg; 60 mg/kg
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Administration:p.o.; once daily 5×/week; 28 days
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Result:Increased bone mineral density by 23.4% compared to ovariectomized control mice.
Ameliorated osteoporosis-related bone loss.
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Animal Model:BALB/C mice with Periodontal disease (8-week-old male; ligature-induced periodontal disease)[1]
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Dosage:20 mg/kg
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Administration:i.p.; daily; 28 days
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Result:Increased alveolar bone mass by 60.7% compared to ligature-induced periodontal disease control mice.
Increased bone volume by 51.9% compared to ligature-induced periodontal disease control mice.
Increased vertical bone remaining at M2-M3 by 67.0% compared to ligature-induced periodontal disease control mice.
Preserved alveolar bone structure.
Chemical Information
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CAS No. 2812381-74-9
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Appearance Solid
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Molecular Weight 419.52
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Formula C28H25N3O
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Color White to off-white
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SMILES
O=C(C1=CC2=C(NC3=C2C=CC=C3)C(CCC4=CC=CC=C4)=N1)NC5=C(C)C=CC=C5C
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
DMSO : 25 mg/mL (59.59 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocols
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RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Mammalian live/dead viability and cytotoxicity staining
Live/dead viability and cytotoxicity staining assays are based on the simultaneous detection of intracellular esterase activity in metabolically active (viable) cells and membrane integrity loss in non-viable cells. In commonly used dual-staining approaches, membrane-permeant fluorogenic substrates are converted by intracellular esterases into fluorescent products in live cells, while impermeant DNA-binding dyes selectively enter cells with compromised plasma membranes and label nucleic acids in dead or dying cells, enabling discrimination between viable and non-viable populations by fluorescence microscopy or flow cytometry.
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Protocol for Pharmacokinetic Study
Pharmacokinetic studies quantify how an organism handles a drug over time through absorption, distribution, metabolism, and excretion, and the core experimental readout is the concentration-time profile of parent drug and, when relevant, metabolites in biological matrices such as plasma, whole blood, urine, bile, or tissue. Pharmacokinetic analysis links dose, route, exposure, clearance, half-life, distribution, bioavailability, and systemic exposure to drug efficacy and toxicity hypotheses rather than measuring a signaling pathway directly. The literature links pharmacokinetics to drug-development phenotypes by showing that drug metabolism and pharmacokinetics influence compound progression, exposure-response interpretation, safety margins, dosing strategy, and failure risk during discovery and development. DMPK science contributes to compound optimization by integrating physicochemical properties, in vitro metabolism, transporter behavior, in vivo exposure, and pharmacodynamic contex
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Osteoclast differentiation from monocyte/macrophage precursors
Osteoclast differentiation is an in vitro induction assay in which monocyte/macrophage-lineage precursors are exposed to macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL), generating multinucleated osteoclasts that are commonly identified by tartrate-resistant acid phosphatase (TRAP) staining and functionally confirmed by resorption pits on dentin, bone, or mineralized substrates. M-CSF supports survival and expansion of osteoclast precursors, while RANKL binding to RANK drives osteoclast commitment, fusion, maturation, and resorptive function; osteoprotegerin inhibits this pathway by binding RANKL and preventing RANK activation. The main readouts are the number of TRAP-positive multinucleated cells, formation of F-actin rings, and resorbed surface area; TRAP-positive multinucleated cells indicate osteoclast differentiation, whereas pit formation on dentin, bone, or mineralized coating indicates functional bone-resorbing activity.
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Phalloidin F-actin cytoskeleton staining
Phalloidin F-actin staining detects polymerized filamentous actin in fixed and permeabilized specimens by using fluorescent phalloidin or phalloidin-derived phallotoxins that bind actin filaments and generate a fluorescence microscopy readout corresponding to F-actin organization, including stress fibers, cortical actin, filament bundles, and tissue-specific actin networks. Phalloidin stabilizes F-actin by reducing actin subunit dissociation from filament ends, and fluorescent phallotoxins were established as tools for visualizing actin-containing structures in eukaryotic cells.
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Cell Viability Determination by MTT Colorimetric Assay
The following protocol uses the MTT colorimetric assay as a classic literature-established method for assessing cell viability/metabolic activity in cultured mammalian cells. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] is reduced by metabolically active cells to a colored formazan product; the amount of formazan is quantified spectrophotometrically and provides an indirect measure of metabolically active viable cells. Importantly, MTT reduction reflects cellular oxidoreductase/metabolic activity rather than an absolute direct count of living cells, so changes in cellular metabolism can alter the signal independently of cell number.
Purity & Documentation
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Data Sheet (287 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.3837 mL | 11.9184 mL | 23.8368 mL | 59.5919 mL |
| 5 mM | 0.4767 mL | 2.3837 mL | 4.7674 mL | 11.9184 mL | |
| 10 mM | 0.2384 mL | 1.1918 mL | 2.3837 mL | 5.9592 mL | |
| 15 mM | 0.1589 mL | 0.7946 mL | 1.5891 mL | 3.9728 mL | |
| 20 mM | 0.1192 mL | 0.5959 mL | 1.1918 mL | 2.9796 mL | |
| 25 mM | 0.0953 mL | 0.4767 mL | 0.9535 mL | 2.3837 mL | |
| 30 mM | 0.0795 mL | 0.3973 mL | 0.7946 mL | 1.9864 mL | |
| 40 mM | 0.0596 mL | 0.2980 mL | 0.5959 mL | 1.4898 mL | |
| 50 mM | 0.0477 mL | 0.2384 mL | 0.4767 mL | 1.1918 mL |
Y1693 Related Classifications
HY-182757 Related Classifications
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