Lumacaftor
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MedKoo CAT#: 510211

CAS#: 936727-05-8

Description: Lumacaftor, also known as VX-809, is a potent CFTR corrector, many be useful for treatment of patients with cystic fibrosis who have a phe508del CFTR mutation. Cystic fibrosis (CF) is a genetic disorder that causes multiorgan morbidity and premature death, most commonly from pulmonary dysfunction.


Chemical Structure

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Lumacaftor
CAS# 936727-05-8

Theoretical Analysis

MedKoo Cat#: 510211
Name: Lumacaftor
CAS#: 936727-05-8
Chemical Formula: C24H18F2N2O5
Exact Mass: 452.11838
Molecular Weight: 452.41
Elemental Analysis: C, 63.72; H, 4.01; F, 8.40; N, 6.19; O, 17.68

Price and Availability

Size Price Availability Quantity
200.0mg USD 150.0 Same day
500.0mg USD 250.0 Same day
1.0g USD 450.0 Same day
2.0g USD 850.0 Same day
5.0g USD 1650.0 Same day
10.0g USD 2950.0 2 Weeks
20.0g USD 3950.0 2 Weeks
50.0g USD 6950.0 2 Weeks
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Synonym: VX-809; VX809; VX 809; VRT-826809; VRT 826809; VRT826809; Lumacaftor; Orkambi;

IUPAC/Chemical Name: 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid

InChi Key: UFSKUSARDNFIRC-UHFFFAOYSA-N

InChi Code: InChI=1S/C24H18F2N2O5/c1-13-5-8-19(27-20(13)14-3-2-4-15(11-14)21(29)30)28-22(31)23(9-10-23)16-6-7-17-18(12-16)33-24(25,26)32-17/h2-8,11-12H,9-10H2,1H3,(H,29,30)(H,27,28,31)

SMILES Code: O=C(O)C1=CC=CC(C2=NC(NC(C3(C4=CC=C(OC(F)(F)O5)C5=C4)CC3)=O)=CC=C2C)=C1

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

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: >2 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: Lumacaftor (VX-809; VRT 826809) is a CFTR modulator that corrects the folding and trafficking of CFTR protein.
In vitro activity: Fig. 7 shows that wt-ABCA4 colocalizes nicely with cadherin demonstrating that it is indeed located at the plasma membrane. Its membrane localization is not affected by treatment with VX-809. Fig. 8 & 9 shows that VX-809 restores the membrane localization of both mutants. The surface biotinylation and confocal microscopy experiments agree that rank order of the effect of VX-809 is G1961E >A1038V >ABCA4. Given that ABCA4 functions at the plasma membrane these data add more evidence that VX-809 maybe therapeutic for Stargardt disease. Reference: Cell Physiol Biochem. 2019; 53(2): 400–412. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027368/
In vivo activity: VX-809 has the surprising ability to restore renal cells in ADPKD to a noncyst-forming phenotype, including negating the ability of cAMP to sustain and stimulate cyst growth. A key result is that VX-809 reduced Hsp27, Hsp70, and Hsp90, which are known to be up-regulated in cancer cells to protect the proteins in abnormally dividing cells. Although the CFTR is a major driver of cyst growth, it is apparently not a major player in the normal kidney, because patients with CF do not have kidney disease. VX-809, in removing the cyst's ability to grow in the presence of high levels of cAMP and inhibiting Ca2+ release by the ER, turns off or reduces two major signal transduction pathways that fuel cyst growth (see Fig. 13). Given that administration of VX-809 has already been shown to be safe, it could offer a new approach for treating patients with ADPKD. Reference: J Biol Chem. 2018 Jul 20; 293(29): 11513–11526. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065164/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 56.67 125.26
DMSO:PBS (pH 7.2) (1:3) 0.25 0.55
DMF 30.0 66.31
Ethanol 19.5 43.1

Preparing Stock Solutions

The following data is based on the product molecular weight 452.41 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. Liu Q, Sabirzhanova I, Bergbower EAS, Yanda M, Guggino WG, Cebotaru L. The CFTR Corrector, VX-809 (Lumacaftor), Rescues ABCA4 Trafficking Mutants: a Potential Treatment for Stargardt Disease. Cell Physiol Biochem. 2019;53(2):400-412. doi: 10.33594/000000146. PMID: 31403270; PMCID: PMC7027368. 2. Krainer G, Treff A, Hartmann A, Stone TA, Schenkel M, Keller S, Deber CM, Schlierf M. A minimal helical-hairpin motif provides molecular-level insights into misfolding and pharmacological rescue of CFTR. Commun Biol. 2018 Sep 28;1:154. doi: 10.1038/s42003-018-0153-0. PMID: 30302398; PMCID: PMC6162264. 3. Yanda MK, Liu Q, Cebotaru L. A potential strategy for reducing cysts in autosomal dominant polycystic kidney disease with a CFTR corrector. J Biol Chem. 2018 Jul 20;293(29):11513-11526. doi: 10.1074/jbc.RA118.001846. Epub 2018 Jun 6. PMID: 29875161; PMCID: PMC6065164. 4. Liu H, Luo K, Luo D. Guanosine monophosphate reductase 1 is a potential therapeutic target for Alzheimer's disease. Sci Rep. 2018 Feb 9;8(1):2759. doi: 10.1038/s41598-018-21256-6. PMID: 29426890; PMCID: PMC5807363.
In vitro protocol: 1. Liu Q, Sabirzhanova I, Bergbower EAS, Yanda M, Guggino WG, Cebotaru L. The CFTR Corrector, VX-809 (Lumacaftor), Rescues ABCA4 Trafficking Mutants: a Potential Treatment for Stargardt Disease. Cell Physiol Biochem. 2019;53(2):400-412. doi: 10.33594/000000146. PMID: 31403270; PMCID: PMC7027368. 2. Krainer G, Treff A, Hartmann A, Stone TA, Schenkel M, Keller S, Deber CM, Schlierf M. A minimal helical-hairpin motif provides molecular-level insights into misfolding and pharmacological rescue of CFTR. Commun Biol. 2018 Sep 28;1:154. doi: 10.1038/s42003-018-0153-0. PMID: 30302398; PMCID: PMC6162264.
In vivo protocol: 1. Yanda MK, Liu Q, Cebotaru L. A potential strategy for reducing cysts in autosomal dominant polycystic kidney disease with a CFTR corrector. J Biol Chem. 2018 Jul 20;293(29):11513-11526. doi: 10.1074/jbc.RA118.001846. Epub 2018 Jun 6. PMID: 29875161; PMCID: PMC6065164. 2. Liu H, Luo K, Luo D. Guanosine monophosphate reductase 1 is a potential therapeutic target for Alzheimer's disease. Sci Rep. 2018 Feb 9;8(1):2759. doi: 10.1038/s41598-018-21256-6. PMID: 29426890; PMCID: PMC5807363.

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1: 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.

2: 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.

3: 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.

4: 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.

5: 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.

6: 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.

7: 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.

8: 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.

9: 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.

10: 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.

11: 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.

Lumacaftor

200.0mg / USD 150.0


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