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| Targets |
Calcium-sensing receptor (CaSR). Calindol hydrochloride is a potent and selective allosteric modulator of the CaSR. It functions as a positive allosteric modulator (PAM), meaning it binds to a site distinct from the orthosteric (calcium) binding site and enhances the receptor's activity. It has been shown to activate a CaSR mutant that lacks the extracellular ligand-binding domain, confirming its allosteric mode of action.
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| ln Vitro |
In cells expressing rat or human CaSR, respectively, calindol stimulates phosphatidylinositol (PI) with an EC50 of 1.0 μM or 0.31 μM in the presence of 2 mM Ca2+ [2]. Calindol (1-10 µM) inhibits whole-cell voltage-gated Ca2+ channel (VGCC) currents in rabbit mesenteric arteries and precontract tone induced by KCl and methoxamine in line myography studies [3].
Calindol hydrochloride is a potent CaSR PAM with an EC50 of 132 nM. It stimulates phosphatidylinositol (PI) hydrolysis in cells expressing the rat or human CaSR, with EC50 values of 1.0 μM and 0.31 μM, respectively, in the presence of 2 mM Ca2+. It also inhibits Pi-induced vascular calcification (VC), delaying its progression in vascular smooth muscle cells. |
| ln Vivo |
In vivo, Calindol hydrochloride is used to study the effects of CaSR modulation. By acting as a PAM, it can potentiate the effects of extracellular calcium, leading to downstream effects such as the inhibition of Pi-induced vascular calcification. This makes it a useful compound for researching disorders like vascular calcification, which is a common complication in chronic kidney disease and other cardiovascular conditions.
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| Enzyme Assay |
In vitro receptor binding studies for allosteric modulators like Calindol hydrochloride typically involve radioligand binding assays using membranes from cells expressing the CaSR. These assays can determine if the compound binds to an allosteric site by examining its effect on the binding of a known orthosteric ligand. Functional assays, such as measuring Ca2+-evoked intracellular calcium mobilization or PI hydrolysis in CaSR-expressing cells, are used to confirm its PAM activity and determine its EC50.
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| Cell Assay |
The in vitro cellular activity of Calindol hydrochloride is evaluated using cell lines that endogenously or heterologously express the CaSR. Cells are treated with the compound in the presence of varying concentrations of extracellular Ca2+. The potentiation of CaSR-mediated signaling, such as an increase in intracellular calcium or PI hydrolysis, is then measured. This allows for the determination of its EC50 for PAM activity, which has been reported as 132 nM.
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| Animal Protocol |
In vivo studies with Calindol hydrochloride would typically be performed in animal models of vascular calcification or other CaSR-related diseases. The compound would be administered, and its effects on disease progression, such as the inhibition of vascular calcification, would be assessed. Its impact on systemic calcium homeostasis and other downstream effects of CaSR activation would also be monitored to understand its pharmacodynamic profile.
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| ADME/Pharmacokinetics |
As a small molecule (molecular weight: 336.86, formula: C21H21ClN2), Calindol hydrochloride is soluble in DMSO. Its pharmacokinetic properties, such as absorption, distribution, metabolism, and excretion (ADME), would be characteristic of a typical small-molecule allosteric modulator. While specific PK data is limited, its use in research suggests it has sufficient bioavailability for in vivo studies.
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| Toxicity/Toxicokinetics |
No specific toxicity data is available for Calindol hydrochloride. As a CaSR PAM, its safety profile would be of interest. Potential toxicities could be related to over-activation of the CaSR, which could lead to hypocalcemia or other disturbances in mineral ion homeostasis. Standard preclinical safety studies would be required to evaluate its potential for adverse effects before any clinical application.
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| References |
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| Additional Infomation |
Calindol hydrochloride (CAS#: 729610-18-8) is a potent and selective positive allosteric modulator (PAM) of the calcium-sensing receptor (CaSR). It is a research tool used to study CaSR biology, particularly in the context of cardiovascular disease. Its EC50 for CaSR modulation is 132 nM. It is not approved for clinical use and is intended for research purposes only.
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| Molecular Formula |
C21H21CLN2
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| Molecular Weight |
336.86
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| Exact Mass |
336.139
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| CAS # |
729610-18-8
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| Related CAS # |
374933-30-9
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| PubChem CID |
23544608
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| Appearance |
White to light yellow solid powder
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| LogP |
6.364
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
1
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
24
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| Complexity |
382
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C[C@H](C1=CC=CC2=CC=CC=C21)NCC3=CC4=CC=CC=C4N3.Cl
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| InChi Key |
KFILKQPBQZIRST-XFULWGLBSA-N
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| InChi Code |
InChI=1S/C21H20N2.ClH/c1-15(19-11-6-9-16-7-2-4-10-20(16)19)22-14-18-13-17-8-3-5-12-21(17)23-18;/h2-13,15,22-23H,14H2,1H3;1H/t15-;/m1./s1
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| Chemical Name |
(1R)-N-(1H-indol-2-ylmethyl)-1-naphthalen-1-ylethanamine;hydrochloride
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| Synonyms |
Calindol Hydrochloride; 729610-18-8; Calindol (hydrochloride); (1R)-N-(1H-indol-2-ylmethyl)-1-naphthalen-1-ylethanamine;hydrochloride; [(1H-indol-2-yl)methyl][(1R)-1-(naphthalen-1-yl)ethyl]amine hydrochloride
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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 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)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (296.9 mM)
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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 | 2.9686 mL | 14.8430 mL | 29.6859 mL | |
| 5 mM | 0.5937 mL | 2.9686 mL | 5.9372 mL | |
| 10 mM | 0.2969 mL | 1.4843 mL | 2.9686 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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