 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C24H28N2O3 |
| Molecular Weight | 411.607798576355 |
| Exact Mass | 411.329 |
| CAS # | 1413431-22-7 |
| Related CAS # | Ivacaftor;873054-44-5;Ivacaftor-d9;1413431-07-8;Ivacaftor-d4;Ivacaftor benzenesulfonate;1134822-09-5;Ivacaftor hydrate;1134822-07-3 |
| PubChem CID | 156589027 |
| Appearance | Typically exists as solid at room temperature |
| Density | 1.2±0.1 g/cm3 |
| Boiling Point | 550.5±50.0 °C at 760 mmHg |
| Flash Point | 286.7±30.1 °C |
| Vapour Pressure | 0.0±1.5 mmHg at 25°C |
| Index of Refraction | 1.606 |
| LogP | 6.34 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 29 |
| Complexity | 619 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O=C1C2=CC=CC=C2NC=C1C(=O)NC1C=C(O)C(C(C([2H])([2H])[2H])(C([2H])([2H])[2H])C([2H])([2H])[2H])=C([2H])C=1C(C([2H])([2H])[2H])(C([2H])([2H])[2H])C([2H])([2H])[2H] |
| InChi Key | JCCGBCJGTQQUSZ-NZXNCOHNSA-N |
| InChi Code | InChI=1S/C24H36N2O3/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/h11-12,14-15,18,25,27H,7-10,13H2,1-6H3,(H,26,29)/i1D3,2D3,3D3,4D3,5D3,6D3,11D |
| Chemical Name | N-[3-deuterio-2,4-bis[1,1,1,3,3,3-hexadeuterio-2-(trideuteriomethyl)propan-2-yl]-5-hydroxyphenyl]-4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinoline-3-carboxamide |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| ln Vitro | "During the drug development process, stable heavy isotopes of carbon, hydrogen, and other elements have been incorporated into drug molecules primarily as quantitative tracers. Because deuteration may alter a drug's pharmacokinetics and metabolism, it is concerning. Range [1]. Potential benefits of compounds with deuteration: (1) Increase the body's half-life. Deuterated substances may be able to lengthen the compound's half-life in the body, or its pharmacokinetic properties. This may enhance the compound's tolerance, efficacy, and safety. acceptance and improve administration convenience. Boost oral bioavailability, second. Deuterated compounds have the potential to mitigate the degree of undesirable metabolism, also known as first-pass metabolism, in the liver and intestinal wall, thereby increasing the amount of drugs that remain unmetabolized. Get to the intended action site. Its better tolerance and activity at low doses are determined by its high bioavailability. (3) Enhance the properties of metabolism. Deuterated substances may be able to enhance medications by lowering the production of hazardous or reactive metabolites. state of metabolism. (4) Boost the security of medications. Deuterated compounds are safe and have the potential to lessen or eliminate the negative side effects of drug compounds. (5) Preserve medicinal qualities. According to earlier research, deuterated compounds should maintain characteristics similar to those of hydrogen analogs. Potency and selectivity of biochemistry. Ivacaftor-d19 |
| References |
[1]. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-216. [2]. Functional defect of variants in the adenosine triphosphate-binding sites of ABCB4 and their rescue by the cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor (VX-770). Hepatology. 2017 Feb;65(2):560-570. [3]. Therapeutic benefit observed with the CFTR potentiator, ivacaftor, in a CF patient homozygous for the W1282X CFTR nonsense mutation. J Cyst Fibros. 2017 Jan;16(1):24-29. [4]. Discovery of N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (VX-770, ivacaftor), a potent and orally bioavailable CFTR potentiator. J Med Chem. 2014 Dec 11;57(23):9776-9. [5]. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18825-30. |
Solubility Data
| 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 |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4295 mL | 12.1474 mL | 24.2948 mL | |
| 5 mM | 0.4859 mL | 2.4295 mL | 4.8590 mL | |
| 10 mM | 0.2429 mL | 1.2147 mL | 2.4295 mL |