| Size | Price | Stock | Qty |
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| 10mg |
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| Other Sizes |
| Targets |
CaV1.3 1.7 μM (IC50)
The primary target of CaV1.3 antagonist-1 is the CaV1.3 subunit of L-type voltage-gated calcium channels (LTCCs, also known as Cav1.3). It is a selective small-molecule inhibitor targeting the CaV1.3 subtype, with an IC50 of 1.7 uM. CaV1.3 channels are predominantly expressed in neurons (including dopaminergic neurons of the substantia nigra and striatum) and in cardiac pacemaker cells, where they contribute to Ca2+ influx and regulate neuronal excitability, neurotransmitter release, cardiac automaticity, and gene expression. |
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| ln Vitro |
In HEK293 cells, CaV1.3 and CaV1.2 channel currents are inhibited by CaV1.3 antagonist-1 (Compound 8; 5 μM) by 31.2% and 4.4%, respectively. This is consistent with the FLIPR assay results [1].
In vitro, CaV1.3 antagonist-1 potently and selectively inhibits CaV1.3 L-type calcium channels. At a concentration of 5 uM, the compound inhibits CaV1.3 channel currents by 31.2% in HEK293 cells, while only inhibiting CaV1.2 channel currents by 4.4% under identical conditions, representing greater than 600-fold selectivity for CaV1.3 over CaV1.2. This high selectivity makes CaV1.3 antagonist-1 one of the most selective small-molecule CaV1.3 inhibitors available, as most clinically used L-type calcium channel blockers (e.g., nifedipine, verapamil, diltiazem) are not selective for CaV1.3 over CaV1.2. |
| ln Vivo |
Specific in vivo activity data for CaV1.3 antagonist-1 is not provided in the available references. As a selective CaV1.3 antagonist, the compound would be expected to have effects in animal models of Parkinson‘s disease (CaV1.3 channels are expressed in dopaminergic neurons and may contribute to neurodegeneration), epilepsy (CaV1.3 channels regulate neuronal excitability), depression (CaV1.3 channels modulate mood-related circuits), and atrial arrhythmias (CaV1.3 channels are expressed in cardiac pacemaker cells). However, specific in vivo efficacy data has not been reported.
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| Enzyme Assay |
The activity of CaV1.3 antagonist-1 is measured by whole-cell patch-clamp electrophysiology, not by a typical cell-free binding assay. HEK293 cells are transiently or stably transfected with cDNAs encoding the human CaV1.3 alpha1 subunit along with the auxiliary beta and alpha2delta subunits to reconstitute functional L-type calcium channels. Cells are voltage-clamped at a holding potential of -80 mV to -100 mV, and test depolarizations (e.g., to +10 mV or 0 mV) are applied to activate CaV channels. Varying concentrations of CaV1.3 antagonist-1 (e.g., 0.1-100 uM) are applied via bath perfusion. The reduction in peak calcium current amplitude relative to the vehicle control is measured to calculate the IC50 (1.7 uM) and to determine selectivity (by comparing inhibition of CaV1.3 vs. CaV1.2 currents).
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| Cell Assay |
For cellular assays, HEK293 cells or SH-SY5Y neuroblastoma cells (which endogenously express CaV1.3 channels) are used. Cells are loaded with a Ca2+-sensitive fluorescent dye (e.g., Fluo-4 AM or Fura-2 AM) and placed on a fluorescence plate reader or an inverted microscope. Cells are treated with varying concentrations of CaV1.3 antagonist-1 (0.1-100 uM) for 10-30 minutes, and then KCl (50 mM) is added to depolarize the cells and activate voltage-gated calcium channels, causing Ca2+ influx. The reduction in the fluorescence signal (indicating reduced Ca2+ influx) is measured to assess functional CaV1.3 blockade. For more precise measurements, patch-clamp is preferred over bulk Ca2+ imaging.
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| Animal Protocol |
For an in vivo efficacy study, a mouse model of Parkinson's disease (e.g., MPTP-induced dopaminergic neuron degeneration or 6-OHDA-lesioned rats) or epilepsy (e.g., pentylenetetrazol (PTZ)-induced seizure model) would be used. CaV1.3 antagonist-1 would be administered intraperitoneally (e.g., 1-20 mg/kg) or orally, and behavioral endpoints (locomotor activity, seizure latency, depression-like behavior in forced swim test) would be assessed. Neuroprotection would be evaluated by counting tyrosine hydroxylase (TH)-positive dopaminergic neurons in the substantia nigra pars compacta. However, specific protocols have not been published for this compound.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for CaV1.3 antagonist-1 is not provided in the available references. As a small molecule with an IC50 of 1.7 uM for CaV1.3 (a relatively modest potency compared to the low nanomolar potency of many CNS drugs), sufficient brain penetration and CNS exposure would be required for in vivo efficacy. The compound is a cyclopentyl analog, which may have moderate lipophilicity and could be formulated in standard vehicles (e.g., 10% DMSO, 40% PEG300, 5% Tween 80, 45% saline) for intraperitoneal or oral administration. Further ADME studies are needed to characterize its in vivo behavior.
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| Toxicity/Toxicokinetics |
No detailed toxicological data is provided for CaV1.3 antagonist-1. L-type calcium channels are widely expressed throughout the body, and CaV1.3 channels in particular are important for cardiac pacemaker activity (sinus node automaticity) and neuroendocrine function (insulin secretion, hearing). Selective CaV1.3 blockade could theoretically cause bradycardia, arrhythmias, and metabolic disturbances. The high selectivity for CaV1.3 over CaV1.2 (>600-fold) may minimize the hypotension and reflex tachycardia often seen with non-selective L-type blockers, but comprehensive toxicology studies are needed. The compound is a research tool, not a clinical candidate, and is not intended for human use.
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| References | |
| Additional Infomation |
CaV1.3 antagonist-1 is a unique pharmacological tool because it is one of the few small molecules that selectively inhibits CaV1.3 L-type calcium channels over the closely related CaV1.2 channels. Most clinically approved L-type calcium channel blockers (nifedipine, amlodipine, verapamil, diltiazem) have only modest (2-10 fold) selectivity for CaV1.2 over CaV1.3 and are used to treat hypertension and angina by acting primarily on cardiovascular CaV1.2. CaV1.3 channels are highly expressed in the central nervous system (dopaminergic neurons, hippocampal neurons, striatal neurons) and in cardiac pacemaker cells, making them potential drug targets for Parkinson's disease (neuroprotection by reducing Ca2+ overload in dopaminergic neurons), epilepsy (reducing neuronal hyperexcitability), and sinus node dysfunction. This compound provides a research tool to dissect the specific roles of CaV1.3 vs. CaV1.2 channels in physiology and disease. At 5 uM, it inhibits CaV1.3 currents by 31.2% while inhibiting CaV1.2 by only 4.4%, demonstrating >600-fold selectivity.
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| Molecular Formula |
C17H19CLN2O3
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|---|---|
| Molecular Weight |
334.80
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| Exact Mass |
334.108
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| CAS # |
1391385-57-1
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| PubChem CID |
57520395
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| Appearance |
White to light yellow solid powder
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| LogP |
3.1
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
23
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| Complexity |
490
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CCC(C1)N2C(=O)CC(=O)N(C2=O)CCC3=CC(=CC=C3)Cl
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| InChi Key |
AJKSBVCOTKODMF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H19ClN2O3/c18-13-5-3-4-12(10-13)8-9-19-15(21)11-16(22)20(17(19)23)14-6-1-2-7-14/h3-5,10,14H,1-2,6-9,11H2
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| Chemical Name |
1-[2-(3-chlorophenyl)ethyl]-3-cyclopentyl-1,3-diazinane-2,4,6-trione
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 (298.69 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 | 2.9869 mL | 14.9343 mL | 29.8686 mL | |
| 5 mM | 0.5974 mL | 2.9869 mL | 5.9737 mL | |
| 10 mM | 0.2987 mL | 1.4934 mL | 2.9869 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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