Ivacaftor
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MedKoo CAT#: 507210

CAS#: 873054-44-5

Description: Ivacaftor, also known as VX-770, is a drug used to treat cystic fibrosis in people with certain mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, who account for 4–5% cases of cystic fibrosis, and is included in a combination drug, lumacaftor/ivacaftor, which is used to treat people with cystic fibrosis who have the F508del mutation in CFTR. Ivacaftor is a "potentiator" of CFTR, meaning it increases the probability that the defective channel will be open and allow chloride ions pass through the channel pore.


Chemical Structure

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Ivacaftor
CAS# 873054-44-5

Theoretical Analysis

MedKoo Cat#: 507210
Name: Ivacaftor
CAS#: 873054-44-5
Chemical Formula: C24H28N2O3
Exact Mass: 392.20999
Molecular Weight: 392.49072
Elemental Analysis: C, 73.44; H, 7.19; N, 7.14; O, 12.23

Price and Availability

Size Price Availability Quantity
500.0mg USD 150.0 Same day
1.0g USD 250.0 Same day
2.0g USD 450.0 Same day
5.0g USD 1010.0 Same day
10.0g USD 1810.0 Same day
20.0g USD 3250.0 Same day
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Synonym: VX770; VX 770; VX-770; Ivacaftor; brand name: KALYDECO; Orkambi.

IUPAC/Chemical Name: N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide

InChi Key: PURKAOJPTOLRMP-UHFFFAOYSA-N

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)

SMILES Code: O=C(C1=CNC2=C(C=CC=C2)C1=O)NC3=CC(O)=C(C(C)(C)C)C=C3C(C)(C)C

Appearance: Solid powder

Purity: >98%

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >5 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: Ivacaftor (VX-770) is a potent CFTR potentiator, targeting G551D-CFTR and F508del-CFTR with EC50s of 100 nM and 25 nM, respectively.
In vitro activity: The aim of this in vitro study was to evaluate the effect of ivacaftor on mutant CFTR protein forms with defects in protein processing and/or channel function. The effect of ivacaftor on CFTR function was tested in electrophysiological studies using a panel of Fischer rat thyroid (FRT) cells expressing 54 missense CFTR mutations that cause defects in the amount or function of CFTR at the cell surface. Acute (5-min) addition of ivacaftor following CFTR activation by forskolin significantly (P = 0.05; paired t-test) increased chloride transport over baseline for a number of the mutant CFTR forms tested (Table 2; Fig. 2B). The net increase over baseline chloride transport by ivacaftor (ivacaftor response minus baseline) ranged from 1.8 to 155.0% of normal CFTR, reaching maximum sustained levels of 2.1 to 200.7% of normal CFTR (Table 2; Fig. 2B). The fold increase over baseline chloride transport (ivacaftor response divided by baseline) ranged from 1.6 to 52.0 (Table 2). The EC50 of ivacaftor for all mutant CFTR forms tested was similar to G551D-CFTR (range; 101 to 735 nM) (Table 2; Fig. 3). The remaining mutant CFTR forms had no significant response to ivacaftor under the experimental conditions used in this study (Table 2; Fig. 2B). In conclusion, ivacaftor potentiated multiple mutant CFTR forms produced by missense CFTR mutations expressed in a panel of FRT cells. These in vitro studies along with in vivo measures of residual CFTR function, such as exocrine pancreatic function or sweat chloride concentrations, could be used to help stratify patients with CF who have different CFTR genotypes for studies investigating the potential clinical benefit of ivacaftor. Reference: J Cyst Fibros. 2014 Jan;13(1):29-36. https://pubmed.ncbi.nlm.nih.gov/23891399/
In vivo activity: TBD

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 50.0 127.39

Preparing Stock Solutions

The following data is based on the product molecular weight 392.49072 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Van Goor F, Yu H, Burton B, Hoffman BJ. Effect of ivacaftor on CFTR forms with missense mutations associated with defects in protein processing or function. J Cyst Fibros. 2014 Jan;13(1):29-36. doi: 10.1016/j.jcf.2013.06.008. Epub 2013 Jul 23. PMID: 23891399. 2. Yu H, Burton B, Huang CJ, Worley J, Cao D, Johnson JP Jr, Urrutia A, Joubran J, Seepersaud S, Sussky K, Hoffman BJ, Van Goor F. Ivacaftor potentiation of multiple CFTR channels with gating mutations. J Cyst Fibros. 2012 May;11(3):237-45. doi: 10.1016/j.jcf.2011.12.005. Epub 2012 Jan 30. PMID: 22293084.
In vitro protocol: 1. Van Goor F, Yu H, Burton B, Hoffman BJ. Effect of ivacaftor on CFTR forms with missense mutations associated with defects in protein processing or function. J Cyst Fibros. 2014 Jan;13(1):29-36. doi: 10.1016/j.jcf.2013.06.008. Epub 2013 Jul 23. PMID: 23891399. 2. Yu H, Burton B, Huang CJ, Worley J, Cao D, Johnson JP Jr, Urrutia A, Joubran J, Seepersaud S, Sussky K, Hoffman BJ, Van Goor F. Ivacaftor potentiation of multiple CFTR channels with gating mutations. J Cyst Fibros. 2012 May;11(3):237-45. doi: 10.1016/j.jcf.2011.12.005. Epub 2012 Jan 30. PMID: 22293084.
In vivo protocol: TBD

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1: Hoy SM. Elexacaftor/Ivacaftor/Tezacaftor: First Approval. Drugs. 2019 Dec;79(18):2001-2007. doi: 10.1007/s40265-019-01233-7. Review. PubMed PMID: 31784874.

2: Tezacaftor/ivacaftor for cystic fibrosis. Aust Prescr. 2019 Oct;42(5):174-175. doi: 10.18773/austprescr.2019.060. Epub 2019 Sep 13. Review. PubMed PMID: 31631935; PubMed Central PMCID: PMC6787300.

3: Lumacaftor/ivacaftor for cystic fibrosis. Aust Prescr. 2019 Oct;42(5):170-171. doi: 10.18773/austprescr.2019.058. Epub 2019 Sep 13. Review. PubMed PMID: 31631933; PubMed Central PMCID: PMC6787305.

4: Lommatzsch ST, Taylor-Cousar JL. The combination of tezacaftor and ivacaftor in the treatment of patients with cystic fibrosis: clinical evidence and future prospects in cystic fibrosis therapy. Ther Adv Respir Dis. 2019 Jan-Dec;13:1753466619844424. doi: 10.1177/1753466619844424. Review. PubMed PMID: 31027466; PubMed Central PMCID: PMC6487765.

5: Clinical Review Report: Lumacaftor/Ivacaftor (Orkambi): (Vertex Pharmaceuticals (Canada) Incorporated): Indication: For the treatment of cystic fibrosis in patients aged six years and older who are homozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator gene [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2018 Oct. Available from http://www.ncbi.nlm.nih.gov/books/NBK540356/ PubMed PMID: 31013018.

6: Pharmacoeconomic Review Report: Lumacaftor/Ivacaftor (Orkambi): (Vertex Pharmaceuticals (Canada) Incorporated): Indication: For the treatment of cystic fibrosis in patients 6 years of age and older who are homozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator gene [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2018 Oct. Available from http://www.ncbi.nlm.nih.gov/books/NBK540212/ PubMed PMID: 30998303.

7: CADTH Canadian Drug Expert Committee Recommendation: Lumacaftor/Ivacaftor (Orkambi — Vertex Pharmaceuticals (Canada) Incorporated): Indication: Cystic fibrosis, F508del-cystic fibrosis transmembrane conductance regulator gene mutation in patients aged six years and older [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2018 Oct. No abstract available. Available from http://www.ncbi.nlm.nih.gov/books/NBK540016/ PubMed PMID: 30973690.

8: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from http://www.ncbi.nlm.nih.gov/books/NBK534421/ PubMed PMID: 30507114.

9: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from http://www.ncbi.nlm.nih.gov/books/NBK534420/ PubMed PMID: 30489718.

10: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from http://www.ncbi.nlm.nih.gov/books/NBK513062/ PubMed PMID: 30000992.

11: Bulloch MN, Hanna C, Giovane R. Lumacaftor/ivacaftor, a novel agent for the treatment of cystic fibrosis patients who are homozygous for the F580del CFTR mutation. Expert Rev Clin Pharmacol. 2017 Oct;10(10):1055-1072. doi: 10.1080/17512433.2017.1378094. Epub 2017 Sep 22. Review. PubMed PMID: 28891346.

12: Talamo Guevara M, McColley SA. The safety of lumacaftor and ivacaftor for the treatment of cystic fibrosis. Expert Opin Drug Saf. 2017 Nov;16(11):1305-1311. doi: 10.1080/14740338.2017.1372419. Epub 2017 Sep 21. Review. PubMed PMID: 28846049; PubMed Central PMCID: PMC6209511.

13: Schneider EK, Reyes-Ortega F, Li J, Velkov T. Can Cystic Fibrosis Patients Finally Catch a Breath With Lumacaftor/Ivacaftor? Clin Pharmacol Ther. 2017 Jan;101(1):130-141. doi: 10.1002/cpt.548. Epub 2016 Nov 23. Review. PubMed PMID: 27804127; PubMed Central PMCID: PMC5191968.

14: Deeks ED. Lumacaftor/Ivacaftor: A Review in Cystic Fibrosis. Drugs. 2016 Aug;76(12):1191-201. doi: 10.1007/s40265-016-0611-2. Review. PubMed PMID: 27394157.

15: Dryden C, Wilkinson J, Young D, Brooker RJ; Scottish Paediatric Cystic Fibrosis Managed Clinical Network (SPCFMCN). The impact of 12 months treatment with ivacaftor on Scottish paediatric patients with cystic fibrosis with the G551D mutation: a review. Arch Dis Child. 2018 Jan;103(1):68-70. doi: 10.1136/archdischild-2015-310420. Epub 2016 Jun 10. Review. PubMed PMID: 27288428.

16: Zhang W, Zhang X, Zhang YH, Strokes DC, Naren AP. Lumacaftor/ivacaftor combination for cystic fibrosis patients homozygous for Phe508del-CFTR. Drugs Today (Barc). 2016 Apr;52(4):229-37. doi: 10.1358/dot.2016.52.4.2467205. Review. PubMed PMID: 27252987; PubMed Central PMCID: PMC5495103.

17: McColley SA. A safety evaluation of ivacaftor for the treatment of cystic fibrosis. Expert Opin Drug Saf. 2016 May;15(5):709-15. doi: 10.1517/14740338.2016.1165666. Epub 2016 Apr 7. Review. PubMed PMID: 26968005.

18: Ivacaftor (Kalydeco) 150 mg Tablet: For Treatment of Cystic Fibrosis with G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, or G970R Mutation [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2015 Jul. Available from http://www.ncbi.nlm.nih.gov/books/NBK349151/ PubMed PMID: 26962591.

19: Kuk K, Taylor-Cousar JL. Lumacaftor and ivacaftor in the management of patients with cystic fibrosis: current evidence and future prospects. Ther Adv Respir Dis. 2015 Dec;9(6):313-26. doi: 10.1177/1753465815601934. Epub 2015 Sep 28. Review. PubMed PMID: 26416827.

20: Kapoor H, Koolwal A, Singh A. Ivacaftor: a novel mutation modulating drug. J Clin Diagn Res. 2014 Nov;8(11):SE01-5. doi: 10.7860/JCDR/2014/6486.5158. Epub 2014 Nov 20. Review. PubMed PMID: 25584290; PubMed Central PMCID: PMC4290359.

Ivacaftor

500.0mg / USD 150.0


Additional Information

KALYDECO (ivacaftor, VX-770) is Vertex's lead medicine in development for the treatment of people with cystic fibrosis. Known as a CFTR potentiator, this oral medicine in development aims to help CFTR protein function more normally once it reaches the cell surface, which is believed to help hydrate and clear mucus from the airways. Vertex retains worldwide rights to develop and commercialize KALYDECO (kuh-LYE-deh-koh). The brand name KALYDECO has been approved by the EMA and provisionally approved by the FDA, but KALYDECO has not been granted marketing authorization or approval from any regulatory authority.
 
About Cystic Fibrosis : CF is a life-threatening genetic disease affecting approximately 30,000 people in the United States and 70,000 people worldwide. Today, the median predicted age of survival for a person with CF is approximately 38 years. According to the 2010 Cystic Fibrosis Foundation Patient Registry Annual Data Report, approximately 4 percent of the total CF patient population in the United States have at least one copy of the G551D mutation. The most common form of CF is caused by the F508del mutation, which is present in nearly 90 percent of people with the disease.