| Size | Price | Stock | Qty |
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| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
CTP-656 targets the cystic fibrosis transmembrane conductance regulator (CFTR) protein, a chloride channel on the surface of epithelial cells. As a CFTR potentiator, it increases the probability of channel opening, thereby improving the flow of salt and water across cell membranes. It is particularly effective in patients with the G551D gating mutation, and has also shown activity in cells with the F508del mutation. In G551D/F508del HBE cells, it exhibits an EC50 of 255 nM for CFTR potentiation.
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| ln Vitro |
In vitro, CTP-656 acts as a potent CFTR modulator. It enhances CFTR function in primary human bronchial epithelial (HBE) cells carrying the G551D/F508del mutations, with an EC50 of 255 nM. As a deuterated form of Ivacaftor, it is expected to have a similar mechanism of action, potentiating the open probability of the CFTR channel, but with potentially improved metabolic stability.
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| ln Vivo |
In PK studies, CTP-656 (oral gavage; 10 mg/kg; single dose) demonstrated excellent pharmacokinetic profiles. The compound's plasma levels were measured over a 72-hour period, revealing parameters such as Cmax, AUC0-24 1970 ng/ml (15%), 24,260 hr*ng/ml (17%), 413 ng/ml (19%), and 13.9 hr at 2 hr in hr, C24hr, and t1/male Sprague-Dawley rats, respectively. In male Beagle dogs (3.0 mg/kg), the values Cmax, AUC0-24 hours, C24 hours, and t1/2 of CTP-656 (oral gavage; 3 mg/kg; single dose) were 3643 ng/ml (9%), 49,782 hr*ng/ml (31%) and 22.8 hours.
In vivo, CTP-656 has demonstrated excellent pharmacokinetic profiles in preclinical species. In pharmacokinetic studies, CTP-656 (oral gavage; 10 mg/kg; single dose) in male Sprague-Dawley rats showed Cmax of 1970 ng/ml, AUC0-24 of 24,260 hr*ng/ml, and a half-life of 13.9 hours. In male Beagle dogs (3 mg/kg), the Cmax was 3643 ng/ml, AUC0-24 was 49,782 hr*ng/ml, and half-life was 22.8 hours. |
| Enzyme Assay |
In cell-free receptor binding or enzymatic assays, CTP-656's activity is evaluated by measuring its ability to potentiate CFTR channel function in membrane preparations. The compound is incubated with CFTR protein, and chloride ion flux is measured using fluorescent indicators or electrophysiological techniques. The potentiation of channel activity is determined by comparing the response in the presence and absence of the compound, and the EC50 is calculated from the concentration-response curve.
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| Cell Assay |
In vitro cell-based experiments with CTP-656 typically involve the use of primary human bronchial epithelial (HBE) cells or cell lines expressing mutant CFTR (e.g., G551D or F508del). Cells are cultured and treated with varying concentrations of the compound. The function of the CFTR channel is then assessed by measuring the rate of chloride efflux using a fluorescent dye (e.g., SPQ) or by using an Ussing chamber to measure short-circuit current (Isc) across the epithelial monolayer.
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| Animal Protocol |
In vivo animal experiments with CTP-656 have been conducted primarily for pharmacokinetic studies. Male Sprague-Dawley rats and Beagle dogs are administered the compound via oral gavage at specific doses (e.g., 10 mg/kg for rats, 3 mg/kg for dogs). Blood samples are collected at various time points over a 72-hour period, and plasma concentrations of CTP-656 are measured using LC-MS/MS to determine pharmacokinetic parameters such as Cmax, AUC, and half-life.
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| ADME/Pharmacokinetics |
CTP-656 is designed as a deuterated analog of Ivacaftor to improve pharmacokinetic properties by reducing metabolic clearance. In preclinical PK studies, the compound demonstrated a long half-life of 13.9 hours in rats and 22.8 hours in dogs after oral administration. It is orally bioavailable and shows favorable exposure profiles. The compound's metabolism is expected to be slower than Ivacaftor due to the deuterium isotope effect, leading to a prolonged duration of action.
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| Toxicity/Toxicokinetics |
No specific toxicity data is publicly available for CTP-656 beyond its use in clinical trials. As a CFTR potentiator, its safety profile is expected to be similar to that of Ivacaftor, which is generally well-tolerated. Common adverse effects may include headache, upper respiratory tract infection, and gastrointestinal disturbances. The compound is for research use only and is not intended for human therapeutic use outside of approved clinical trials.
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| References | |
| Additional Infomation |
Deutivacaftor is being studied in the clinical trial NCT03227471 (the VX-445 study, which involved healthy subjects and patients with cystic fibrosis).
CTP-656 is a deuterated CFTR potentiator also known as Deutivacaftor, Ivacaftor-d9, or VX-561. Its molecular formula is C24H19D9N2O3 and its molecular weight is 401.55. The compound has been studied in clinical trials (e.g., NCT03227471) for cystic fibrosis. It is not yet approved by regulatory agencies and is available for research purposes only. It represents a next-generation CFTR modulator with potentially improved pharmacokinetic properties over Ivacaftor. |
| Molecular Formula |
C24H19D9N2O3
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|---|---|
| Molecular Weight |
401.5539
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| Exact Mass |
401.266
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| CAS # |
1413431-07-8
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| Related CAS # |
Ivacaftor;873054-44-5;Ivacaftor-d4;Ivacaftor-d19;1413431-22-7
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| PubChem CID |
71470491
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
550.5±50.0 °C at 760 mmHg
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| Flash Point |
286.7±30.1 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.606
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| LogP |
6.34
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
29
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| Complexity |
671
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[2H]C([2H])([2H])C(C1=C(C=C(C(=C1)C(C)(C)C)NC(=O)C2=CNC3=CC=CC=C3C2=O)O)(C([2H])([2H])[2H])C([2H])([2H])[2H]
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| InChi Key |
PURKAOJPTOLRMP-ASMGOKTBSA-N
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| InChi Code |
InChI=1S/C24H28N2O3/c1-23(2,3)16-11-17(24(4,5)6)20(27)12-19(16)26-22(29)15-13-25-18-10-8-7-9-14(18)21(15)28/h7-13,27H,1-6H3,(H,25,28)(H,26,29)/i4D3,5D3,6D3
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| Chemical Name |
N-[2-tert-butyl-4-[1,1,1,3,3,3-hexadeuterio-2-(trideuteriomethyl)propan-2-yl]-5-hydroxyphenyl]-4-oxo-1H-quinoline-3-carboxamide
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| Synonyms |
CTP-656; CTP-656; CTP-656
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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) |
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
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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 | 2.4903 mL | 12.4517 mL | 24.9035 mL | |
| 5 mM | 0.4981 mL | 2.4903 mL | 4.9807 mL | |
| 10 mM | 0.2490 mL | 1.2452 mL | 2.4903 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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