| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
|
| Targets |
Calcium channel
|
|---|---|
| ln Vitro |
Norverapamil hydrochloride, also known as (±)-norverapamil, is just as efficient as vitamin D in decreasing isoniazid and rifampicin tolerance and killing intracellular Mycobacterium tuberculosis when used alone. Similar is Lapami. Similar serum levels to verapamil can be attained by norverapamil, which can likewise prevent tolerance generated by macrophages [1]. As CYP3A substrates and mechanism-based inhibitors, verapamil and its primary metabolite norverapamil were found to have nonlinear pharmacokinetics in the clinic [3].
|
| ln Vivo |
The primary metabolite of verapamil is norverapamil hydrochloride (9 mg/kg; oral), which has the following values: terminal half-life, AUC, and Cmax: 9.4 hours, 260 ng▯h/ml, and 41.6 ng/mL, respectively. [4].
|
| Cell Assay |
Drug tolerance likely represents an important barrier to tuberculosis treatment shortening. We previously implicated the Mycobacterium tuberculosis efflux pump Rv1258c as mediating macrophage-induced tolerance to rifampicin and intracellular growth. In this study, we infected the human macrophage-like cell line THP-1 with drug-sensitive and drug-resistant M. tuberculosis strains and found that tolerance developed to most antituberculosis drugs, including the newer agents moxifloxacin, PA-824, linezolid, and bedaquiline. Multiple efflux pump inhibitors in clinical use for other indications reversed tolerance to isoniazid and rifampicin and slowed intracellular growth. Moreover, verapamil reduced tolerance to bedaquiline and moxifloxacin. Verapamil's R isomer and its metabolite norverapamil have substantially less calcium channel blocking activity yet were similarly active as verapamil at inhibiting macrophage-induced drug tolerance. Our finding that verapamil inhibits intracellular M. tuberculosis growth and tolerance suggests its potential for treatment shortening. Norverapamil, R-verapamil, and potentially other derivatives present attractive alternatives that may have improved tolerability[1].
|
| Animal Protocol |
Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat [3]
Doses: 9 mg/kg (pharmacokinetic/PK/PK study) Route of Administration: Oral Experimental Results: t1/2=9.4 hrs (hrs (hours)); AUC=260 ng·h/ml; Cmax =41.6ng/ml. |
| References |
|
| Molecular Formula |
C26H37CLN2O4
|
|---|---|
| Molecular Weight |
477.04
|
| Exact Mass |
476.244185
|
| Elemental Analysis |
C, 65.46; H, 7.82; Cl, 7.43; N, 5.87; O, 13.42
|
| CAS # |
67812-42-4
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| Related CAS # |
Norverapamil;67018-85-3
|
| PubChem CID |
155002
|
| Appearance |
Typically exists as white to off-white solids at room temperature
|
| Melting Point |
155-160℃ dec.
|
| LogP |
2.024
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
33
|
| Complexity |
577
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
N#CC(C(C)C)(CCCNCCC1=CC=C(OC)C(OC)=C1)C2=CC=C(OC)C(OC)=C2.[H]Cl
|
| InChi Key |
OEAFTRIDBHSJDC-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C26H36N2O4.ClH/c1-19(2)26(18-27,21-9-11-23(30-4)25(17-21)32-6)13-7-14-28-15-12-20-8-10-22(29-3)24(16-20)31-5;/h8-11,16-17,19,28H,7,12-15H2,1-6H3;1H
|
| Chemical Name |
2-(3,4-Dimethoxyphenyl)-5-[2-(3,4-dimethoxyphenyl)ethylamino]-2-propan-2-ylpentanenitrile hydrochloride
|
| Synonyms |
Norverapamil HCl; Norverapamil hydrochloride; Norverapamil hydrochloride; Norverapamil, Hydrochloride; Nor Verapamil Hydrochloride; Norverapamil (hydrochloride); Norverapamil HCl; 2-(3,4-dimethoxyphenyl)-5-[2-(3,4-dimethoxyphenyl)ethylamino]-2-propan-2-ylpentanenitrile hydrochloride; 2-(3,4-dimethoxyphenyl)-5-[2-(3,4-dimethoxyphenyl)ethylamino]-2-propan-2-ylpentanenitrile;hydrochloride;
|
| 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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
H2O : ≥ 50 mg/mL (~104.81 mM)
DMSO : ≥ 31 mg/mL (~64.98 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.24 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.24 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0963 mL | 10.4813 mL | 20.9626 mL | |
| 5 mM | 0.4193 mL | 2.0963 mL | 4.1925 mL | |
| 10 mM | 0.2096 mL | 1.0481 mL | 2.0963 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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