Tezacaftor | VX-661 | CAS#1152311-62-0 | CFTR modulator

MedKoo Cat#: 510264 | Name: Tezacaftor (VX-661)

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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

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: 520.1821

Molecular Weight: 520.50

Elemental Analysis: C, 60.00; H, 5.23; F, 10.95; N, 5.38; O, 18.44

Price and Availability

Size	Price	Availability
5mg	USD 90.00	Ready to Ship
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,650.00	Ready to ship
1g	USD 4,250.00	2 weeks

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Related CAS #

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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

More Info

Product Data

Product Data

Certificate of Analysis

View current batch of CoA, Lot#BBC40409

QC Data

View QC data: current batch, Lot#BBC40409

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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

	Solvent	mg/mL	mM
Solubility
	DMSO	102.0	195.67

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 520.50 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.

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:

In vivo protocol:

TBD

1: Ausloos I, Vanbrabant T, Paeps M, Havermans T, Vandenberghe J, Dupont L. Mentaal welzijn na behandeling met elexacaftor/tezacaftor/ivacaftor bij eindstadium van mucoviscidose [Mental health after treatment with elexacaftor/tezacaftor/ivacaftor in end-stage cystic fibrosis]. Tijdschr Psychiatr. 2024;66(10):579-585. Dutch. PMID: 39749592. 2: Kurita GP, Eidemak I, Pressier T, Larsen S, Sjøgren P, Lykke C. Palliative care needs in cystic fibrosis: hospital survey. BMJ Support Palliat Care. 2024 Dec 31:spcare-2024-005318. doi: 10.1136/spcare-2024-005318. Epub ahead of print. PMID: 39740962. 3: Gerges M, Chiasson M, Nichols C, Morrison N, De B. Possible drug-interaction between elexacaftor-tezacaftor-ivacaftor and repaglinide in an adult with cystic fibrosis-related diabetes. Can J Diabetes. 2024 Dec 26:S1499-2671(24)00413-1. doi: 10.1016/j.jcjd.2024.12.003. Epub ahead of print. PMID: 39732285. 4: Sütering T, Bode SFN, Fischer R, Fabricius D. Successful Therapy over 12 Months of People with Cystic Fibrosis with Rare Non-phe508del Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutations with Elexacaftor/Tezacaftor/Ivacaftor (ETI). Adv Respir Med. 2024 Dec 20;92(6):559-572. doi: 10.3390/arm92060049. PMID: 39727500; PMCID: PMC11672886. 5: Rose NR, Bailey J, Anderson JD, Chalamalla AR, Ryan KJ, Acosta EP, Guimbellot JS. Pilot and feasibility study of dietary composition with elexacaftor- tezacaftor-ivacaftor concentrations in people with cystic fibrosis. Pharmacotherapy. 2024 Dec;44(12):920-926. doi: 10.1002/phar.4630. Epub 2024 Dec 23. PMID: 39716404. 6: Kam CW, McKinzie CJ, Omecene NE, Peters S, Pettit RS, Poisson MO, Witte J. Papilledema in Children With Cystic Fibrosis Receiving Elexacaftor/Tezacaftor/Ivacaftor: A Multicenter Case Series. Pediatr Pulmonol. 2024 Dec 20:e27455. doi: 10.1002/ppul.27455. Epub ahead of print. PMID: 39704064. 7: Lévêque M, Mirval S, Barrault C, Fixe I, Coraux C, Sage E, Becq F, Vandebrouck C. The F508del-CFTR trafficking correctors elexacaftor and tezacaftor are CFTR-independent Ca2+-mobilizing agonists normalizing abnormal Ca2+ levels in human airway epithelial cells. Respir Res. 2024 Dec 19;25(1):436. doi: 10.1186/s12931-024-03059-8. PMID: 39702307; PMCID: PMC11660580. 8: Bani Melhim S, Douglas LEJ, Reihill JA, Downey DG, Martin SL. The effect of triple CFTR modulator therapy and azithromycin on ion channels and inflammation in cystic fibrosis. ERJ Open Res. 2024 Dec 16;10(6):00502-2024. doi: 10.1183/23120541.00502-2024. PMID: 39687397; PMCID: PMC11647873. 9: Barbosa MA, Vendrusculo FM, Epifanio M, Donadio MVF, Pinto LA. Short-term effects of elexacaftor/tezacaftor/ivacaftor in pediatric cystic fibrosis patients in Brazil: a case series. J Bras Pneumol. 2024 Dec 6;50(5):e20230403. doi: 10.36416/1806-3756/e20230403. PMID: 39661831; PMCID: PMC11601090. 10: Chan CL, Shirley Bezerra M, Stefanovski D, Gallop RJ, Walega R, Donaldson SH, Frederick CA, Freedman SD, Gelfond D, Hoffman LR, Narkewicz MR, Rowe SM, Sagel SD, Schwarzenberg SJ, Solomon GM, Stalvey MS, Kelly A. Glycemia and Insulin Secretion in Cystic Fibrosis Two Years After Elexacaftor/Tezacaftor/Ivacaftor: PROMISE-ENDO. J Clin Endocrinol Metab. 2024 Dec 9:dgae857. doi: 10.1210/clinem/dgae857. Epub ahead of print. PMID: 39657947. 11: Leo-Hansen C, Faurholt-Jepsen D, Qvist T, Højte C, Nielsen BU, Bryrup T, Henriksen EH, Katzenstein T, Skov M, Mathiesen IHM, Jeppesen M, Jensen-Fangel S, Olesen HV, Buchvald FF, Nielsen KG, Jimenez-Solem E, Ritz C, Pressler T, Olsen MF; TransformCF Study Group. Lung function improvement on triple modulators: high-resolution, nationwide data from the Danish Cystic Fibrosis Cohort. ERJ Open Res. 2024 Dec 9;10(6):00339-2024. doi: 10.1183/23120541.00339-2024. PMID: 39655171; PMCID: PMC11626609. 12: Gramegna A, Ruscica M, Leonardi G, Macchi C, Fichtner I, Putti G, Schianca MC, Terranova L, Alicandro G, Blasi F. Cardiometabolic risk factors in adults with cystic fibrosis undergoing elexacaftor/tezacaftor/ivacaftor therapy. J Cyst Fibros. 2024 Dec 6:S1569-1993(24)01844-7. doi: 10.1016/j.jcf.2024.11.009. Epub ahead of print. PMID: 39645478. 13: Metcalf A, Martiniano SL, Sagel SD, Zaretsky MV, Zemanick ET, Hoppe JE. Outcomes of prenatal use of elexacaftor/tezacaftor/ivacaftor in carrier mothers to treat meconium ileus in fetuses with cystic fibrosis. J Cyst Fibros. 2024 Dec 6:S1569-1993(24)01843-5. doi: 10.1016/j.jcf.2024.11.011. Epub ahead of print. PMID: 39645477. 14: Heching M, Shteinberg M, Golan-Tripto I, Livnat-Levanon G, Yaacoby-Bianu K, Boehm Cohen L, Hazan G, Slomianski L, Prais D, Mussaffi H, Weinberg J, Kramer MR. Treatment effects of elexacaftor/tezacaftor/ivacaftor on people with cystic fibrosis heterozygous for 3849+10kbC->T and a class I variant. J Cyst Fibros. 2024 Dec 5:S1569-1993(24)01845-9. doi: 10.1016/j.jcf.2024.11.010. Epub ahead of print. PMID: 39643544. 15: Zhu Y, Wu M, Li D, Habgood M, Chinnery HR, Schneider-Futschik EK. Lens- related ocular changes in fetal rats following in-utero exposure to elexacaftor- tezacaftor-ivacaftor. J Cyst Fibros. 2024 Dec 5:S1569-1993(24)01851-4. doi: 10.1016/j.jcf.2024.11.014. Epub ahead of print. PMID: 39643543. 16: Milczewska J, Syunyaeva Z, Żabińska-Jaroń A, Sands D, Thee S. Changing profile of bacterial infection and microbiome in cystic fibrosis: when to use antibiotics in the era of CFTR-modulator therapy. Eur Respir Rev. 2024 Dec 4;33(174):240068. doi: 10.1183/16000617.0068-2024. PMID: 39631927; PMCID: PMC11615665. 17: Martín de Vicente C, Cáceres Barrera SJ, Fuentes Sánchez C, Gutiérrez Alonso C, García Romero R. Acute cholecystitis as an adverse effect of treatment with elexacaftor/tezacaftor/ivacaftor in a patient with cystic fibrosis. An Pediatr (Engl Ed). 2024 Dec;101(6):413-414. doi: 10.1016/j.anpede.2024.11.006. Epub 2024 Dec 2. PMID: 39627094. 18: Oppelaar MC, van Helvoort HA, Bannier MA, Reijers MH, van der Vaart H, van der Meer R, Altenburg J, Conemans L, Rottier BL, Nuijsink M, van den Wijngaart LS, Merkus PJ, Roukema J. Accuracy, Reproducibility, and Responsiveness to Treatment of Home Spirometry in Cystic Fibrosis: Multicenter, Retrospective, Observational Study. J Med Internet Res. 2024 Dec 3;26:e60892. doi: 10.2196/60892. PMID: 39626236; PMCID: PMC11653036. 19: Kerem E. Expanding the Impact of New Cystic Fibrosis Therapies in Low- and Middle-Income Countries. Pediatr Pulmonol. 2024 Dec 3:e27362. doi: 10.1002/ppul.27362. Epub ahead of print. PMID: 39625248. 20: Tomati V, Capurro V, Pesce E, Pastorino C, Sondo E, Lena M, Borrelli A, Cresta F, Pantano S, Collini F, Ripani P, Terlizzi V, Fevola C, Costa S, Lucanto MC, Zara F, Bandiera T, Bocciardi R, Castellani C, Galietta LJV, Pedemonte N. Pharmacological rescue of the G85E CFTR variant by preclinical and approved modulators. Front Pharmacol. 2024 Nov 18;15:1494327. doi: 10.3389/fphar.2024.1494327. PMID: 39624835; PMCID: PMC11608983.