| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Targets |
Encaleret selectively targets the calcium-sensing receptor (CaSR) and acts as an antagonist. It exerts its effect by inhibiting the excessive activity of functional gain-of-function CaSR variants. As a negative allosteric modulator, it binds to a site distinct from the orthosteric calcium-binding site, reducing the receptor's sensitivity to calcium. This leads to the restoration of blood calcium levels, promotion of PTH secretion, improvement of magnesium and phosphorus metabolism, and an increase in urinary calcium excretion. Encaleret has an IC₅₀ of 12 nM.
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| ln Vitro |
In vitro, encaleret has been shown to be a potent antagonist of the calcium-sensing receptor (CaSR), with an IC₅₀ of 12 nM. It inhibits the excessive activity of functional gain-of-function CaSR variants. By antagonizing CaSR, encaleret can restore blood calcium levels and promote the secretion of parathyroid hormone (PTH). These in vitro activities form the basis for its potential therapeutic applications in conditions like osteoporosis and autosomal dominant hypocalcemia.
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| ln Vivo |
In vivo, encaleret has demonstrated efficacy in restoring blood calcium levels and promoting PTH secretion. Its oral bioavailability makes it a convenient agent for administration in preclinical and clinical studies. Encaleret has shown promise in treating autosomal dominant hypocalcemia (ADH1) by modulating the CaSR, and Phase 3 clinical trials have been reported.
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| Enzyme Assay |
Non-cellular assays for encaleret involve assessing its binding affinity and functional activity at the calcium-sensing receptor (CaSR). Radioligand binding displacement studies can be performed using membrane preparations from cells expressing the human CaSR, incubated with a radiolabeled CaSR ligand and varying concentrations of encaleret. Functional assays can measure the compound's ability to inhibit CaSR-mediated intracellular calcium mobilization in response to extracellular calcium, using cell lines expressing the receptor and a calcium-sensitive fluorescent dye.
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| Cell Assay |
In vitro cellular assays for encaleret involve treating cells expressing the calcium-sensing receptor (CaSR) with the compound and measuring its effects on receptor-mediated signaling. Cells are loaded with a calcium-sensitive fluorescent dye and stimulated with varying concentrations of extracellular calcium in the presence of encaleret. The decrease in intracellular calcium mobilization, which indicates CaSR antagonism, is measured. The IC₅₀ for antagonism is determined from the dose-response curves.
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| Animal Protocol |
In vivo animal experiments for encaleret have been conducted in models of osteoporosis and autosomal dominant hypocalcemia (ADH1). Animals are treated with encaleret via oral administration, and blood calcium, PTH, and urinary calcium levels are measured to assess the compound's pharmacodynamic effects. In ADH1 models, the compound's ability to restore normocalcemia and improve mineral metabolism is evaluated.
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| ADME/Pharmacokinetics |
Encaleret has a molecular weight of 514.03 and a molecular formula of C₂₉H₃₃ClFNO₄. It is a solid powder that is soluble in DMSO but not in water. For short-term storage (days to weeks), it should be kept dry, dark, and at 0-4°C; for long-term storage (months to years), it should be stored at -20°C. It is available as a free base as well as in various salt forms.
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| Toxicity/Toxicokinetics |
Encaleret is a research compound for laboratory use only and is not yet approved for human therapeutic use. In preclinical studies, it has been generally well-tolerated at therapeutic doses. As a CaSR antagonist, it may cause side effects related to alterations in calcium and PTH levels. Standard laboratory safety precautions should be followed when handling the compound. It may cause skin, eye, and respiratory irritation.
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| References | |
| Additional Infomation |
Encaleret (JIT-305; MK-5442; CAS 787583-71-5) is an orally active, small-molecule negative allosteric modulator (calcilytic) of the calcium-sensing receptor (CaSR). It has an IC₅₀ of 12 nM and is being developed for the treatment of osteoporosis and autosomal dominant hypocalcemia (ADH1). Encaleret restores blood calcium levels, promotes PTH secretion, and improves mineral metabolism. It is available from various commercial suppliers for research applications.
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| Molecular Formula |
C29H33CLFNO4
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|---|---|
| Molecular Weight |
514.028031110764
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| Exact Mass |
513.208
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| CAS # |
787583-71-5
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| Related CAS # |
787583-71-5;1214922-52-7 (sulfate);
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| PubChem CID |
46917559
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| Appearance |
White to off-white solid powder
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| LogP |
6.593
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
36
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| Complexity |
694
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC1=CC(=CC=C1C(=O)O)C2=CC=CC=C2[C@@H](C)OC[C@@H](CNC(C)(C)CC3=CC(=C(C=C3)Cl)F)O
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| InChi Key |
UNFHDRVFEQPUEL-DENIHFKCSA-N
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| InChi Code |
InChI=1S/C29H33ClFNO4/c1-18-13-21(10-11-23(18)28(34)35)25-8-6-5-7-24(25)19(2)36-17-22(33)16-32-29(3,4)15-20-9-12-26(30)27(31)14-20/h5-14,19,22,32-33H,15-17H2,1-4H3,(H,34,35)/t19-,22-/m1/s1
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| Chemical Name |
4-[2-[(1R)-1-[(2R)-3-[[1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]ethyl]phenyl]-2-methylbenzoic acid
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| Synonyms |
JIT 305; JIT305; JIT-305
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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 | 1.9454 mL | 9.7271 mL | 19.4541 mL | |
| 5 mM | 0.3891 mL | 1.9454 mL | 3.8908 mL | |
| 10 mM | 0.1945 mL | 0.9727 mL | 1.9454 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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