| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 1g | |||
| Other Sizes |
| Targets |
Upacicalcet targets the calcium-sensing receptor (CaSR), a G protein-coupled receptor that plays a critical role in calcium homeostasis by sensing extracellular calcium levels. CaSR is expressed on parathyroid cells and regulates PTH secretion in response to changes in serum calcium. Upacicalcet acts as a positive allosteric modulator (PAM) and agonist of CaSR, binding to the amino acid binding site of the receptor. By activating CaSR, Upacicalcet inhibits PTH secretion from parathyroid cells, thereby reducing serum iPTH and Ca²⁺ levels. Its EC50 as a CaSR agonist is 10.8 nM.
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| ln Vitro |
In vitro, Upacicalcet is a non-peptide calcimimetic that acts as a CaSR agonist with an EC50 of 10.8 nM. The compound activates CaSR and inhibits PTH secretion from parathyroid cells. Its potency and efficacy have been characterized in cell-based assays using cells expressing CaSR. The compound's ability to reduce PTH secretion and serum Ca²⁺ levels has been demonstrated in vitro.
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| ln Vivo |
In vivo, Upacicalcet reduces serum intact parathyroid hormone (iPTH) and serum Ca²⁺ levels, reducing hypocalcemia and gastrointestinal complications. It is used for the treatment of secondary hyperparathyroidism (SHPT) in patients undergoing hemodialysis. By directly acting on parathyroid cell membrane calcium-sensing receptors, Upacicalcet inhibits excessive PTH secretion, thereby reducing blood PTH levels. Clinical studies have demonstrated the efficacy of Upacicalcet in managing SHPT.
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| Enzyme Assay |
In vitro enzyme/receptor binding (non-cell) assays for Upacicalcet involve measuring its binding affinity to the calcium-sensing receptor (CaSR). Radioligand binding assays using membrane preparations from cells expressing CaSR are performed with a radiolabeled CaSR ligand and varying concentrations of Upacicalcet. Binding affinity (IC50 or Ki) is determined by competitive displacement. CaSR activity is assessed by measuring intracellular calcium mobilization or downstream signaling in cell-based assays.
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| Cell Assay |
In vitro cell-based experiments for Upacicalcet are conducted using cells expressing the calcium-sensing receptor (CaSR). Cells are treated with Upacicalcet at varying concentrations, and intracellular calcium levels are measured using fluorescent calcium indicators. PTH secretion is measured in parathyroid cell cultures. The compound's potency (EC50 = 10.8 nM) is determined from dose-response curves.
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| Animal Protocol |
In vivo animal experiments for Upacicalcet are performed in animal models of secondary hyperparathyroidism. The compound is administered intravenously, and serum iPTH and Ca²⁺ levels are measured. Efficacy in reducing PTH secretion and managing SHPT is assessed. Clinical studies in hemodialysis patients have also been conducted.
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| ADME/Pharmacokinetics |
Upacicalcet is administered intravenously, with pharmacokinetic properties suitable for hemodialysis patients. Detailed pharmacokinetic parameters, including half-life, clearance, and volume of distribution, are available from clinical studies. The compound's PK profile supports its use as an intravenous calcimimetic in the hemodialysis setting.
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| Toxicity/Toxicokinetics |
Preclinical and clinical toxicology studies have been conducted to evaluate the safety profile of Upacicalcet. The compound is generally well-tolerated at therapeutic doses. It reduces hypocalcemia and gastrointestinal complications compared with other calcimimetic agents. The safety profile of Upacicalcet supports its use in the treatment of secondary hyperparathyroidism.
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| References | |
| Additional Infomation |
Upacicalcet is a calcium-sensitive receptor (CaSR) agonist with the potential to treat secondary hyperparathyroidism (SHPT). After administration, Upacicalcet targets and binds to CaSR expressed on the parathyroid cell membrane, thereby inhibiting osteoclast activity and reducing excessive secretion of parathyroid hormone (PTH). This prevents PTH-mediated excessive efflux of phosphorus and calcium from the bone into the bloodstream and restores serum calcium and phosphorus levels to normal. Upacicalcet may reduce fracture risk, decrease the deposition of phosphorus and calcium salts in non-bone tissues, alleviate bone and joint pain, and delay the progression of other diseases associated with elevated PTH levels. CaSR controls calcium homeostasis and regulates PTH release.
Upacicalcet is also known as AJT-240. It is a calcimimetic agent approved or under development for the treatment of secondary hyperparathyroidism (SHPT) in hemodialysis patients. Its mechanism of action as a CaSR agonist with EC50 of 10.8 nM makes it a potent and selective agent for reducing PTH secretion. The compound is not for oral use and is administered intravenously. |
| Molecular Formula |
C11H14CLN3O6S
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|---|---|
| Molecular Weight |
351.763360500336
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| Exact Mass |
351.029
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| CAS # |
1333218-50-0
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| Related CAS # |
Upacicalcet sodium;2052969-18-1;(Rac)-Upacicalcet;2649575-19-7
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| PubChem CID |
53374467
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.6±0.1 g/cm3
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| Index of Refraction |
1.647
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| LogP |
0.74
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
22
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| Complexity |
522
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| Defined Atom Stereocenter Count |
1
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| SMILES |
ClC1=CC(=CC(=C1C)NC(NC[C@@H](C(=O)O)N)=O)S(=O)(=O)O
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| InChi Key |
LHEYGVSDVBEYQF-QMMMGPOBSA-N
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| InChi Code |
InChI=1S/C11H14ClN3O6S/c1-5-7(12)2-6(22(19,20)21)3-9(5)15-11(18)14-4-8(13)10(16)17/h2-3,8H,4,13H2,1H3,(H,16,17)(H2,14,15,18)(H,19,20,21)/t8-/m0/s1
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| Chemical Name |
(2S)-2-amino-3-[(3-chloro-2-methyl-5-sulfophenyl)carbamoylamino]propanoic acid
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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 | 2.8428 mL | 14.2142 mL | 28.4285 mL | |
| 5 mM | 0.5686 mL | 2.8428 mL | 5.6857 mL | |
| 10 mM | 0.2843 mL | 1.4214 mL | 2.8428 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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