| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
Calcium-sensing receptor (CaSR), a Class C G protein-coupled receptor. Calhex 231 hydrochloride (the active isomer) is a negative allosteric modulator (NAM) that binds to the transmembrane domain of CaSR, decreasing its sensitivity to extracellular calcium. The (1R,2R)-isomer has low affinity for the allosteric site.
|
|---|---|
| ln Vitro |
As the inactive isomer, (1R,2R)-Calhex 231 hydrochloride shows negligible activity in CaSR functional assays. Its ability to block Ca2+-induced signaling is minimal. This property is essential for experimental design, as it allows researchers to differentiate target-specific effects of the active isomer from non-specific off-target effects.
|
| ln Vivo |
In vivo, the (1R,2R)-isomer is expected to have no therapeutic activity. While the active Calhex 231 hydrochloride has been shown to attenuate diabetic cardiomyopathy and protect against traumatic hemorrhagic shock by improving mitochondrial function and reducing oxidative stress, the inactive isomer serves as a negative control in these animal models.
|
| Enzyme Assay |
This assay measures CaSR-mediated inositol phosphate (IP) accumulation. HEK293 cells stably expressing CaSR are seeded in 96-well plates and pre-incubated with LiCl to block IP degradation. Cells are treated with various concentrations of the test compound (active isomer or inactive (1R,2R)-isomer) for 30 minutes, then stimulated with CaCl2. Cells are lysed, and IP1 levels are measured via HTRF (Cisbio IP-One kit).
|
| Cell Assay |
HEK293 cells expressing recombinant human CaSR are seeded in 96-well plates overnight. The next day, cells are loaded with Fluo-4 AM calcium dye for 60 minutes. After washing, various concentrations of the test compound (1 nM to 100 microM) are added, followed by stimulation with a submaximal concentration of CaCl2. Fluorescence (ex/em: 488/525 nm) is measured using a fluorescence plate reader.
|
| Animal Protocol |
In rodent models of diabetic cardiomyopathy (DCM) or traumatic hemorrhagic shock, the active compound Calhex 231 hydrochloride is administered (e.g., via intraperitoneal injection at 1 mg/kg) while the (1R,2R)-enantiomer is administered as a control. Parameters such as cardiac function (echocardiography), mitochondrial membrane potential, reactive oxygen species (ROS) levels, and survival rate are assessed.
|
| ADME/Pharmacokinetics |
Pharmacokinetics are expected to be similar between the active and inactive isomers due to identical physicochemical properties. Calhex 231 hydrochloride (active) likely has moderate oral bioavailability and tissue distribution. The compound is primarily metabolized in the liver. Given its use as a research tool, detailed PK parameters are not as extensively published as for clinical candidates.
|
| Toxicity/Toxicokinetics |
As the inactive isomer is not biologically active at the target, it is non-toxic at the concentrations used for control experiments (typically uM range). The active isomer Calhex 231 hydrochloride has been shown to be safe in rodent studies at therapeutic doses (up to 3 mg/kg). No significant hepatotoxicity or nephrotoxicity has been reported.
|
| References |
[1]. Yuan H, et al. Calhex231 Alleviates High Glucose-Induced Myocardial Fibrosis via Inhibiting Itch-Ubiquitin Proteasome Pathway in Vitro. Biol Pharm Bull. 2019 Aug 1;42(8):1337-1344.
[2]. Petrel C1, et al. Modeling and mutagenesis of the binding site of Calhex 231, a novel negative allosteric modulator of the extracellular Ca(2+)-sensing receptor. J Biol Chem. 2003 Dec 5;278(49):49487-94. |
| Additional Infomation |
(1R,2R)-Calhex 231 hydrochloride is a high-purity (>99%) research grade chemical used strictly as an experimental control. It is not intended for human therapeutic use and has not been approved for clinical application. The development of CaSR modulators is an active area of research for cardiovascular diseases, metabolic disorders, and diabetic complications.
|
| Molecular Formula |
C25H28CL2N2O
|
|---|---|
| Molecular Weight |
443.41
|
| Related CAS # |
Calhex 231 hydrochloride;2387505-78-2
|
| Appearance |
White to off-white solid powder
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| 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
|
|---|---|
| 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 | 2.2552 mL | 11.2762 mL | 22.5525 mL | |
| 5 mM | 0.4510 mL | 2.2552 mL | 4.5105 mL | |
| 10 mM | 0.2255 mL | 1.1276 mL | 2.2552 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
