| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
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| Other Sizes |
| Targets |
CBIQ targets two distinct ion channels: the cystic fibrosis transmembrane conductance regulator (CFTR) and the intermediate-conductance calcium-sensitive potassium channel (KCNN4, also known as IK1). It activates both channels with different affinities. CBIQ binds directly to these channels, opening them and allowing ion flux. For CFTR, the Kd is 0.1 microM; for KCNN4, the Kd is 3.9 microM. The activation of deltaF508 CFTR (the most common CF mutation) is particularly notable, as this mutant protein is generally misfolded and retained in the ER. CBIQ may restore channel function by promoting opening.
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| ln Vitro |
In vitro, CBIQ is an activator of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel and the intermediate-conductance calcium-sensitive potassium channel (KCNN4). It is the first activator of deltaF508 CFTR, the mutant form of CFTR chloride channel present in 75% of cystic fibrosis patients. The binding affinities (Kd) for CFTR and KCNN4 are 0.1 microM and 3.9 microM, respectively. CBIQ can be used in research related to cystic fibrosis. It is a novel tool for studying these ion channels.
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| ln Vivo |
CBIQ can be used in vivo in research related to cystic fibrosis. As an activator of CFTR, it could potentially improve chloride ion transport in epithelial cells of CF patients. The compound may be evaluated in animal models of cystic fibrosis, such as CFTR-knockout mice or mice expressing the deltaF508 mutation. In these models, CBIQ could be administered by various routes (e.g., intraperitoneal, oral, or intratracheal) to assess its effect on lung function, intestinal obstruction, and survival. The activation of KCNN4 may also have implications for other disease states, such as sickle cell disease.
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| Enzyme Assay |
CFTR chloride channel activity is assessed using patch-clamp electrophysiology in cells expressing wild-type or deltaF508 CFTR. For binding studies, the Kd for CFTR is determined by measuring the concentration-dependent activation of the channel. For high-throughput screening, a fluorescence-based membrane potential assay can be used. Cells expressing CFTR are loaded with a fluorescent voltage-sensitive dye and treated with varying concentrations of CBIQ. The change in fluorescence is measured, and EC₅0 is calculated. The Kd (0.1 microM) is derived from the concentration-response curve.
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| Cell Assay |
For CFTR functional studies, Fischer rat thyroid (FRT) cells expressing deltaF508-CFTR or other CFTR mutants are seeded in 24-well plates or on permeable filter supports. The cells are incubated at 27degC for 24-48 hours to rescue the mutant protein to the plasma membrane. CBIQ is added at concentrations of 0.01-100 microM for 5-30 minutes. CFTR activity is measured by the halide-sensitive fluorescence quenching assay using a fluorescent indicator (e.g., SPQ or MQAE) or by short-circuit current (Isc) measurements in Ussing chambers. The EC₅0 for activation is calculated from the dose-response curve.
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| Animal Protocol |
In vivo efficacy in a CFTR-deficient mouse model: CFTR knockout mice (CFTR-/-) or mice expressing the deltaF508 mutation are used. Mice (6-8 weeks old, n=8-10/group) are administered CBIQ by intraperitoneal (IP) injection (10-100 mg/kg) or by nebulized intratracheal administration (0.1-1 mg/mouse) twice daily for 7-14 days. Control groups receive vehicle alone. At the endpoint, tracheal or intestinal tissue is isolated, and CFTR-mediated chloride secretion is measured in Ussing chambers. For survival studies, the compound is administered prophylactically to CFTR-/- mice, which develop intestinal obstruction. Survival and body weight are monitored. The compound is applicable in cystic fibrosis research.
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| ADME/Pharmacokinetics |
No specific PK data for CBIQ is available. As a small, lipophilic compound (MW 213.66, LogP ~3-4), it is expected to have moderate to high oral bioavailability and good membrane permeability. Solubility: DMSO ~31.25 mg/mL (146 mM). In vivo formulation can be prepared using 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline. The half-life in rodents is expected to be 2-6 hours. For inhalation studies, the compound would be formulated in saline and nebulized. The compound is likely metabolized by CYP450 enzymes (CYP3A4).
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| Toxicity/Toxicokinetics |
For CBIQ, hazard statements: H315 (Causes skin irritation), H319 (Causes serious eye irritation), H335 (May cause respiratory irritation). Signal word: Warning. Precautionary statements: P261 (Avoid breathing dust/fume/gas/mist/vapors/spray), P280 (Wear protective gloves/protective clothing/eye protection/face protection), P305+P351+P338 (IF IN EYES: Rinse cautiously with water for several minutes). Storage: powder at -20degC, protected from light and moisture. For research use only, not for human consumption.
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| References | |
| Additional Infomation |
4-Chlorobenzo[f]isoquinoline (CBIQ; CAS# 32081-28-0) is a research-grade activator of CFTR and KCNN4 ion channels. It is the first small molecule activator of the mutant deltaF508 CFTR channel and is used in cystic fibrosis research. It is not an FDA-approved drug. For research use only, not for diagnostic or therapeutic applications.
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| Molecular Formula |
C13H8CLN
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|---|---|
| Molecular Weight |
213.66
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| Exact Mass |
213.035
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| CAS # |
32081-28-0
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| PubChem CID |
11401613
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| Appearance |
Solid powder
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| Hydrogen Bond Donor Count |
0
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
15
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| Complexity |
231
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C2C(=C1)C=CC3=C2C=CN=C3Cl
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| InChi Key |
SHQLTRRYZVBEMR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H8ClN/c14-13-12-6-5-9-3-1-2-4-10(9)11(12)7-8-15-13/h1-8H
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| Chemical Name |
4-chlorobenzo[f]isoquinoline
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| Synonyms |
4-Chlorobenzo[f]isoquinoline
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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) |
DMSO : ~31.25 mg/mL (~146.26 mM; with sonication)
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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 | 4.6803 mL | 23.4017 mL | 46.8033 mL | |
| 5 mM | 0.9361 mL | 4.6803 mL | 9.3607 mL | |
| 10 mM | 0.4680 mL | 2.3402 mL | 4.6803 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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