Tezacaftor (VX-661)
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MedKoo CAT#: 510264

CAS#: 1152311-62-0

Description: Tezacaftor, also known asVX-661, is CFTR modulator. VX-661 is potentially useful for treatment of cystic fibrosis disease. Cystic fibrosis (CF) is a genetic disease caused by defects in the CF transmembrane regulator (CFTR) gene, which encodes an epithelial chloride channel. The most common mutation, Δ508CFTR, produces a protein that is misfolded and does not reach the cell membrane. VX-661 can correct trafficking of Δ508CFTR and partially restore chloride channel activity.


Chemical Structure

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Tezacaftor (VX-661)
CAS# 1152311-62-0

Theoretical Analysis

MedKoo Cat#: 510264
Name: Tezacaftor (VX-661)
CAS#: 1152311-62-0
Chemical Formula: C26H27F3N2O6
Exact Mass: 520.18212
Molecular Weight: 520.5
Elemental Analysis: C, 60.00; H, 5.23; F, 10.95; N, 5.38; O, 18.44

Price and Availability

Size Price Availability Quantity
10.0mg USD 150.0 Ready to ship
25.0mg USD 250.0 Ready to ship
50.0mg USD 450.0 Ready to ship
100.0mg USD 650.0 Ready to ship
200.0mg USD 950.0 Ready to ship
500.0mg USD 1750.0 Ready to ship
1.0g USD 2850.0 2 Weeks
2.0g USD 3650.0 2 Weeks
5.0g USD 5650.0 2 Weeks
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Synonym: VX-661; VX661; VX 661; Tezacaftor. Trikafta.

IUPAC/Chemical Name: (R)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide

InChi Key: MJUVRTYWUMPBTR-MRXNPFEDSA-N

InChi Code: InChI=1S/C26H27F3N2O6/c1-24(2,13-33)22-8-14-7-18(17(27)10-19(14)31(22)11-16(34)12-32)30-23(35)25(5-6-25)15-3-4-20-21(9-15)37-26(28,29)36-20/h3-4,7-10,16,32-34H,5-6,11-13H2,1-2H3,(H,30,35)/t16-/m1/s1

SMILES Code: O=C(C1(C2=CC=C(OC(F)(F)O3)C3=C2)CC1)NC4=CC5=C(N(C[C@@H](O)CO)C(C(C)(C)CO)=C5)C=C4F

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: Tezacaftor (VX-661) is a second F508del CFTR corrector.
In vitro activity: Primary CF airway cells were expanded using PneumaCultTM-Ex Plus (StemCell Technologies) medium with no feeder cells or added Rho kinase (ROCK) inhibitor. Differentially passaged CF-HBE cells at the air-liquid interface (ALI) were characterized phenotypically and functionally in response to the CFTR corrector drug VX-661 (Tezacaftor). CF-HBE primary cells, expanded up to six passages (~25 population doublings), differentiated into 3D epithelial cultures as evidenced by trans-epithelial electrical resistance (TEER) of >400 Ohms∙cm2 and presence of pseudostratified columnar ciliated epithelium with goblet cells. However, up to passage five cells from most donors showed increased CFTR-mediated short-circuit currents when treated with the corrector drug, VX-661. Ciliary beat frequency (CBF) also increased with the corrector VX-661. The study of rare CF mutations could benefit from cell expansion and could lead to the design of personalized medicine/treatments. J Cyst Fibros. 2020 Sep;19(5):752-761. https://pubmed.ncbi.nlm.nih.gov/32565193/
In vivo activity: TBD

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 102.0 195.67

Preparing Stock Solutions

The following data is based on the product molecular weight 520.5 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. Rayner RE, Wellmerling J, Osman W, Honesty S, Alfaro M, Peeples ME, Cormet-Boyaka E. In vitro 3D culture lung model from expanded primary cystic fibrosis human airway cells. J Cyst Fibros. 2020 Sep;19(5):752-761. doi: 10.1016/j.jcf.2020.05.007. Epub 2020 Jun 18. PMID: 32565193; PMCID: PMC7796805.
In vitro protocol: 1. Rayner RE, Wellmerling J, Osman W, Honesty S, Alfaro M, Peeples ME, Cormet-Boyaka E. In vitro 3D culture lung model from expanded primary cystic fibrosis human airway cells. J Cyst Fibros. 2020 Sep;19(5):752-761. doi: 10.1016/j.jcf.2020.05.007. Epub 2020 Jun 18. PMID: 32565193; PMCID: PMC7796805.
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: Middleton PG, Mall MA, Dřevínek P, Lands LC, McKone EF, Polineni D, Ramsey BW, Taylor-Cousar JL, Tullis E, Vermeulen F, Marigowda G, McKee CM, Moskowitz SM, Nair N, Savage J, Simard C, Tian S, Waltz D, Xuan F, Rowe SM, Jain R; VX17-445-102 Study Group. Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. N Engl J Med. 2019 Nov 7;381(19):1809-1819. doi: 10.1056/NEJMoa1908639. Epub 2019 Oct 31. PubMed PMID: 31697873.

3: Erratum: Profile Of Tezacaftor/Ivacaftor Combination And Its Potential In The Treatment Of Cystic Fibrosis [Erratum]. Ther Clin Risk Manag. 2019 Oct 11;15:1207. doi: 10.2147/TCRM.S232419. eCollection 2019. PubMed PMID: 31696867; PubMed Central PMCID: PMC6795023.

4: Shiferaw D, Faruqi S. Profile of tezacaftor/ivacaftor combination and its potential in the treatment of cystic fibrosis. Ther Clin Risk Manag. 2019 Aug 22;15:1029-1040. doi: 10.2147/TCRM.S165027. eCollection 2019. Erratum in: Ther Clin Risk Manag. 2019 Oct 11;15:1207. PubMed PMID: 31692517; PubMed Central PMCID: PMC6710479.

5: Heijerman HGM, McKone EF, Downey DG, Van Braeckel E, Rowe SM, Tullis E, Mall MA, Welter JJ, Ramsey BW, McKee CM, Marigowda G, Moskowitz SM, Waltz D, Sosnay PR, Simard C, Ahluwalia N, Xuan F, Zhang Y, Taylor-Cousar JL, McCoy KS; VX17-445-103 Trial Group. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1940-1948. doi: 10.1016/S0140-6736(19)32597-8. Epub 2019 Oct 31. PubMed PMID: 31679946.

6: 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.

7: Paterson SL, Barry PJ, Horsley AR. Tezacaftor and ivacaftor for the treatment of cystic fibrosis. Expert Rev Respir Med. 2020 Jan;14(1):15-30. doi: 10.1080/17476348.2020.1682998. Epub 2019 Oct 31. PubMed PMID: 31626570.

8: Walker S, Flume P, McNamara J, Solomon M, Chilvers M, Chmiel J, Harris RS, Haseltine E, Stiles D, Li C, Ahluwalia N, Zhou H, Owen CA, Sawicki G; VX15-661-113 Investigator Group. A phase 3 study of tezacaftor in combination with ivacaftor in children aged 6 through 11 years with cystic fibrosis. J Cyst Fibros. 2019 Sep;18(5):708-713. doi: 10.1016/j.jcf.2019.06.009. Epub 2019 Jun 26. PubMed PMID: 31253540.

9: 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.

10: Garg V, Shen J, Li C, Agarwal S, Gebre A, Robertson S, Huang J, Han L, Jiang L, Stephan K, Wang LT, Lekstrom-Himes J. Pharmacokinetic and Drug-Drug Interaction Profiles of the Combination of Tezacaftor/Ivacaftor. Clin Transl Sci. 2019 May;12(3):267-275. doi: 10.1111/cts.12610. Epub 2019 Jan 29. PubMed PMID: 30694595; PubMed Central PMCID: PMC6510372.

11: 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.

12: Tezacaftor/Ivacaftor (Symdeko) for cystic fibrosis. Med Lett Drugs Ther. 2018 Oct 22;60(1558):174-176. PubMed PMID: 30335045.

13: Davies JC, Moskowitz SM, Brown C, Horsley A, Mall MA, McKone EF, Plant BJ, Prais D, Ramsey BW, Taylor-Cousar JL, Tullis E, Uluer A, McKee CM, Robertson S, Shilling RA, Simard C, Van Goor F, Waltz D, Xuan F, Young T, Rowe SM; VX16-659-101 Study Group. VX-659-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles. N Engl J Med. 2018 Oct 25;379(17):1599-1611. doi: 10.1056/NEJMoa1807119. Epub 2018 Oct 18. PubMed PMID: 30334693; PubMed Central PMCID: PMC6277022.

14: Keating D, Marigowda G, Burr L, Daines C, Mall MA, McKone EF, Ramsey BW, Rowe SM, Sass LA, Tullis E, McKee CM, Moskowitz SM, Robertson S, Savage J, Simard C, Van Goor F, Waltz D, Xuan F, Young T, Taylor-Cousar JL; VX16-445-001 Study Group. VX-445-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles. N Engl J Med. 2018 Oct 25;379(17):1612-1620. doi: 10.1056/NEJMoa1807120. Epub 2018 Oct 18. PubMed PMID: 30334692; PubMed Central PMCID: PMC6289290.

15: Hussar DA, George J. Erenumab-aooe, Benralizumab, and Tezacaftor/ivacaftor. J Am Pharm Assoc (2003). 2018 Sep - Oct;58(5):579-582. doi: 10.1016/j.japh.2018.07.006. PubMed PMID: 30190109.

16: Sala MA, Jain M. Tezacaftor for the treatment of cystic fibrosis. Expert Rev Respir Med. 2018 Sep;12(9):725-732. doi: 10.1080/17476348.2018.1507741. Epub 2018 Aug 9. Review. PubMed PMID: 30073878.

17: Kirby T. Tezacaftor-ivacaftor is safe and efficacious in patients with cystic fibrosis with Phe508del mutations. Lancet Respir Med. 2018 Jan;6(1):13-14. doi: 10.1016/S2213-2600(17)30439-3. Epub 2017 Dec 14. PubMed PMID: 29248431.

18: Taylor-Cousar JL, Munck A, McKone EF, van der Ent CK, Moeller A, Simard C, Wang LT, Ingenito EP, McKee C, Lu Y, Lekstrom-Himes J, Elborn JS. Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del. N Engl J Med. 2017 Nov 23;377(21):2013-2023. doi: 10.1056/NEJMoa1709846. Epub 2017 Nov 3. PubMed PMID: 29099344.

19: Rowe SM, Daines C, Ringshausen FC, Kerem E, Wilson J, Tullis E, Nair N, Simard C, Han L, Ingenito EP, McKee C, Lekstrom-Himes J, Davies JC. Tezacaftor-Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis. N Engl J Med. 2017 Nov 23;377(21):2024-2035. doi: 10.1056/NEJMoa1709847. Epub 2017 Nov 3. PubMed PMID: 29099333; PubMed Central PMCID: PMC6472479.

20: Donaldson SH, Pilewski JM, Griese M, Cooke J, Viswanathan L, Tullis E, Davies JC, Lekstrom-Himes JA, Wang LT; VX11-661-101 Study Group. Tezacaftor/Ivacaftor in Subjects with Cystic Fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR. Am J Respir Crit Care Med. 2018 Jan 15;197(2):214-224. doi: 10.1164/rccm.201704-0717OC. PubMed PMID: 28930490; PubMed Central PMCID: PMC5768901.



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