| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Tiludronate disodium primarily targets osteoclasts. Its molecular targets include the vacuolar-type ATPase (V-ATPase), which is responsible for acidification of the osteoclast resorption lacuna, and protein-tyrosine-phosphatase (PTP), which is involved in maintaining the osteoclast cytoskeletal ring structure.
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|---|---|
| ln Vitro |
Tiludronate inhibits proton transport five times more effectively in vesicles obtained from kidneys (IC50=1.1 mM) than in vesicles derived from osteoclasts (IC50=466 nM). Additionally, tiludronate significantly reduced the activity of pure yeast V-ATPase and impeded proton transport in yeast microsomal preparations (IC50=3.5 microM). Tiludronate quickly and reversibly inhibits the osteoclast V-ATPase-mediated proton transfer, a process that is pH-dependent[3].
In assays using osteoclast-derived vesicles, tiludronate demonstrates potent inhibition of V-ATPase-mediated proton transport (IC50 = 466 nM). This inhibition is rapid, reversible, and pH-dependent. It is less potent against V-ATPase derived from the kidney (IC50 = 1.1 mM). Additionally, it inhibits bacterial collagenase activity. |
| ln Vivo |
Tiludronate inhibits bone resorption in a dose-dependent manner. Mature osteoclasts may be affected by tiludronate by decreased proton secretion into the resorption space and increased dissociation from the bone matrix. In additional osteoporosis models, teludronate is also being tested. Tiludronate (5-200 mg/kg; po) stops the skeletal mass in the castrated male rat model from decreasing. This can be done chemically by checking the calcium and phosphate levels or physically by measuring the weight and density of the bones[3].
In vivo, tiludronate inhibits bone resorption in a dose-dependent manner by reducing proton secretion by mature osteoclasts and promoting their detachment from the bone surface. In a castrated male rat model of osteoporosis, oral administration (5-200 mg/kg) effectively prevents the decrease in bone mass and density. |
| Enzyme Assay |
o assess V-ATPase inhibition, membrane vesicles are isolated from osteoclasts. Vesicles are incubated in a buffer containing Mg-ATP and various concentrations of tiludronate (e.g., 0.1 nM to 100 μM) at 37°C. Proton transport is measured using a fluorescent probe such as Acridine Orange by monitoring fluorescence quenching. The IC50 is calculated by comparing the initial rate of quenching in the presence and absence of the drug.
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| Cell Assay |
Activity is typically assessed using mature osteoclasts isolated from neonatal rabbit long bones and cultured on ivory slices. Cells are treated with increasing concentrations of tiludronate (e.g., 10⁻⁸ M to 10⁻⁴ M) for 48-72 hours. Inhibition of bone resorption is evaluated by measuring the area of resorption pits (e.g., Toluidine Blue staining) or by measuring the release of C-terminal telopeptides of type I collagen (CTX) into the culture medium.
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| Animal Protocol |
Common models include ovariectomized (OVX) rats (postmenopausal osteoporosis) or orchidectomized (ORX) rats (male osteoporosis). Tiludronate is administered daily via oral gavage (e.g., 1, 5, 20 mg/kg) for 4-8 weeks. Efficacy is assessed by measuring bone mineral density (BMD) via DEXA scans, bone strength via biomechanical testing, and urinary deoxypyridinoline (a bone resorption marker).
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| ADME/Pharmacokinetics |
Tiludronic acid has low oral bioavailability (~6% under fasting conditions) and is highly affected by food (bioavailability reduced by 90% when taken with meals). It exhibits high plasma protein binding (~90%). The drug undergoes little to no metabolism. Its primary route of elimination is renal excretion as unchanged drug. The plasma elimination half-life is long (~150 hours) due to slow release from bone.
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| Toxicity/Toxicokinetics |
In clinical studies, the most common adverse effects are gastrointestinal, such as nausea, diarrhea, and dyspepsia. It is associated with a risk of atypical femoral fractures and osteonecrosis of the jaw (ONJ), particularly with long-term use, although the risk is lower compared to nitrogen-containing bisphosphonates. No significant hepato- or nephrotoxicity is observed at standard clinical doses, but it is not recommended for patients with severe renal impairment (CrCl < 30 mL/min).
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| References |
| Molecular Formula |
2[C7H7O6P2SCL-2].4[NA+].H2O
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|---|---|
| Molecular Weight |
371.57
|
| Exact Mass |
741.795
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| CAS # |
155453-10-4
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| Related CAS # |
Tiludronate;89987-06-4; 114084-78-5 (free acid); 149845-07-8 (sodium); 138926-19-9 (sodium hydrate)
|
| PubChem CID |
72941702
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| Appearance |
Typically exists as solid at room temperature
|
| LogP |
5.83
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
15
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| Rotatable Bond Count |
8
|
| Heavy Atom Count |
39
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| Complexity |
320
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O.[Na+].[Na+].[Na+].[Na+].ClC1C=CC(SC(P([O-])(O)=O)P([O-])(O)=O)=CC=1.ClC1C=CC(SC(P([O-])(O)=O)P([O-])(O)=O)=CC=1
|
| InChi Key |
KDVKAYPVWJFARG-UHFFFAOYSA-J
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| InChi Code |
InChI=1S/2C7H9ClO6P2S.4Na.H2O/c2*8-5-1-3-6(4-2-5)17-7(15(9,10)11)16(12,13)14;;;;;/h2*1-4,7H,(H2,9,10,11)(H2,12,13,14);;;;;1H2/q;;4*+1;/p-4
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| Chemical Name |
tetrasodium;[(4-chlorophenyl)sulfanyl-[hydroxy(oxido)phosphoryl]methyl]-hydroxyphosphinate;hydrate
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| Synonyms |
Tiludronate disodium hemihydrate; 155453-10-4; 39SMX0W5WK; tetrasodium;[(4-chlorophenyl)sulfanyl-[hydroxy(oxido)phosphoryl]methyl]-hydroxyphosphinate;hydrate; Tiludronic acid disodium salt hemihydrate [MI];
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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 | 2.6913 mL | 13.4564 mL | 26.9128 mL | |
| 5 mM | 0.5383 mL | 2.6913 mL | 5.3826 mL | |
| 10 mM | 0.2691 mL | 1.3456 mL | 2.6913 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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