Nutrabiotech VX-661 98% 1G Powder, 98% high purity VX-661 (Tezacaftor) powder, selective CFTR corrector, F508del protein trafficking regulator, cystic fibrosis research raw material

CAS 1152311‑62‑0 Tezacaftor Powder VX‑661 F508del‑CFTR Trafficking Modulator for Cystic Fibrosis Research

Tezacaftor powder CAS 1152311‑62‑0, also known as VX‑661, is a well‑studied type‑I CFTR corrector small‑molecule compound. This off‑white crystalline reagent repairs misfolded F508del mutant‑CFTR protein, accelerates protein maturation and boosts CFTR‑ion‑channel trafficking to epithelial cell‑surface. It elevates chloride‑ion transportation on cell‑membrane and is commonly matched together with ivacaftor and elexacaftor for triple‑modulator combination research. Widely applied for cystic‑fibrosis cell‑line testing, CFTR‑protein‑folding mechanism exploration, respiratory‑epithelium‑assay and cystic‑fibrosis‑targeted‑drug screening projects. Every‑batch undergoes strict HPLC purity inspection, bulk‑order service and customizable‑packaging are available for global respiratory‑genetics and biochemistry‑research buyers.

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Tezacaftor (VX-661) CAS 1152311-62-0 | F508del CFTR Corrector for Cystic Fibrosis Research

Tezacaftor (VX-661) CAS 1152311-62-0
F508del CFTR Corrector for Cystic Fibrosis Research

A second-generation CFTR folding corrector that stabilises nascent mutant CFTR — above all the F508del variant — so it escapes endoplasmic reticulum quality control and traffics to the apical plasma membrane of epithelial cells. Tezacaftor is the corrector component of SYMDEKO® (tezacaftor/ivacaftor) and of the transformative triple combination TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor), making it an essential tool compound for CFTR biology, protein folding and trafficking, proteostasis and epithelial ion transport research.

CFTR Corrector F508del Rescue Cystic Fibrosis Protein Trafficking SYMDEKO® Component TRIKAFTA® Component Epithelial Ion Transport
Request a Quote Technical Specs
520.50
MW (C26H27F3N2O6)
≥98%
Purity (HPLC)
F508del
Primary CFTR Target

Molecular Information

Name: Tezacaftor (VX-661)
CAS: 1152311-62-0
Formula: C26H27F3N2O6
MW: 520.50 g/mol
Purity: ≥98% (HPLC)
Solubility: DMSO (~21 mg/mL);
  insoluble in ethanol
SMILES: CC(C)(CO)C1=CC2=CC(=C(C=C2
  N1C[C@H](CO)O)F)NC(=O)C3(CC3)
  C4=CC5=C(C=C4)OC(O5)(F)F
InChIKey: MJUVRTYWUMPBTR
  -MRXNPFEDSA-N
Appearance: White to off-white powder
Synonyms: VX-661 / Tezacaftor
Storage: 2-8°C sealed, protect from light
🧪
CAS Number
1152311-62-0
⚖️
Molecular Weight
520.50
🎯
Primary Activity
CFTR Corrector
✅
Purity
≥98%

Tezacaftor Technical Specifications & Quality Control Data

Complete physicochemical properties, structural identifiers and QC release parameters for research-grade Tezacaftor / VX-661 (CAS 1152311-62-0)

📋 Physicochemical Properties

  • Product NameTezacaftor
  • IUPAC Name1-(2,2-Difluoro-1,3-benzodioxol-5-yl)-N-[1-[(2R)-2,3-dihydroxypropyl]-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)indol-5-yl]cyclopropane-1-carboxamide
  • CAS Number1152311-62-0
  • Development CodeVX-661
  • Combination ProductsSYMDEKO® / SYMKEVI® / TRIKAFTA®
  • Molecular FormulaC26H27F3N2O6
  • Molecular Weight520.50 g/mol
  • Exact Mass520.1821 Da
  • SMILESCC(C)(CO)C1=CC2=CC(=C(C=C2N1C[C@H](CO)O)F)NC(=O)C3(CC3)C4=CC5=C(C=C4)OC(O5)(F)F
  • InChIKeyMJUVRTYWUMPBTR-MRXNPFEDSA-N
  • Stereochemistry1 defined stereocentre (R)
  • AppearanceWhite to off-white powder
  • pKa (predicted)13.99 ± 0.20
  • MDL NumberMFCD23106064
  • PubChem CID46199646
  • EC Number810-780-1

🔬 Quality Control & Handling

  • Purity (HPLC)≥98%
  • Identity1H-NMR / 19F-NMR / LC-MS conform
  • Chiral Purity≥99% ee (chiral HPLC)
  • FormSolid powder
  • ColorWhite to off-white / pale yellow
  • Water Content (KF)≤0.5%
  • Residual SolventsMeets ICH Q3C limits
  • Storage (powder)2-8°C sealed, dry, protect from light
  • Storage (solution)-20°C 6 months / -80°C 1 year
  • SolubilityDMSO ~21 mg/mL (sonication aids dissolution); insoluble in ethanol; poorly soluble in aqueous buffer
  • QC DocumentationCOA / HPLC / NMR / MS / MSDS
  • Pack Sizes1g / 5g / 10g / 100g / 1KG
  • Stock StatusIn Stock
  • Use StatementResearch use only; not for human or clinical use

CFTR Target Engagement & Proteostasis Network

Tezacaftor is a single-target pharmacological chaperone, but rescuing F508del-CFTR reshapes an entire proteostasis and epithelial transport network

🧬 CFTR (ABCC7) — Corrector Class 🧧 F508del-CFTR (Class II Mutation) 🧩 MSD1 Membrane-Spanning Domain 1 🧿 NBD1 / MSD1 Domain Interface 🔄 ER Quality Control Machinery 🗑️ Ubiquitin-Proteasome Degradation 🚚 COPII Vesicle Trafficking 🍳 Golgi Complex Glycosylation (Band C) 🪨 Apical Plasma Membrane Insertion 💧 Epithelial Cl− / HCO3− Transport 🛡️ ENaC Cross-Regulation 🧦 Synergy: Ivacaftor (Potentiator) ➕ Additivity: Elexacaftor (Site-2 Corrector)

How Tezacaftor Works: CFTR Correction Mechanism Step by Step

From co-translational binding in the endoplasmic reticulum to restored chloride secretion at the airway surface — the molecular pathway of F508del rescue

1

The F508del Folding Defect

Deletion of phenylalanine 508 destabilises nucleotide-binding domain 1 (NBD1) and disrupts the NBD1–MSD1 and NBD1–NBD2 domain interfaces. The misfolded protein is recognised by endoplasmic reticulum quality control and never reaches the cell surface.

2

Pharmacological Chaperone Binding

Tezacaftor binds nascent CFTR at a site within membrane-spanning domain 1 (MSD1), acting as a pharmacological chaperone that stabilises the transmembrane helical bundle and the critical NBD1–MSD1 interface during co-translational folding.

3

Escape from ER Degradation

The conformationally stabilised protein evades recognition by the ER-associated degradation (ERAD) machinery, escaping polyubiquitination and proteasomal destruction — the fate of the overwhelming majority of untreated F508del-CFTR.

4

Trafficking & Complex Glycosylation

Rescued CFTR enters COPII vesicles, transits the Golgi and acquires complex N-glycosylation — measurable as the mature "band C" species on Western blot — before being delivered to the apical plasma membrane of the epithelial cell.

5

Potentiation by Ivacaftor

Surface-resident F508del-CFTR still gates poorly. The potentiator ivacaftor binds a distinct site and raises channel open probability, so corrector plus potentiator together deliver far greater chloride current than either mechanism alone.

6

Restored Ion & Fluid Transport

Functional apical CFTR restores Cl− and HCO3− secretion, rehydrating the airway surface liquid, normalising mucus rheology and pH, and improving mucociliary clearance — the endpoint measured as reduced sweat chloride and improved FEV1.

Tezacaftor Research Applications & Experimental Models

VX-661 is the benchmark reference corrector across cystic fibrosis drug discovery, membrane protein folding science and epithelial physiology

🥨

Cystic Fibrosis Drug Discovery

The standard positive-control corrector in CF modulator screening campaigns. Used to benchmark novel correctors for potency, efficacy ceiling and additivity, and as the fixed background against which next-generation site-2 and site-3 correctors are evaluated in F508del rescue assays.

Reference Corrector
🧬

CFTR Structural & Molecular Biology

Applied in cryo-EM, hydrogen-deuterium exchange mass spectrometry, photoaffinity labelling and molecular dynamics studies mapping corrector binding sites within MSD1 and defining how domain interfaces are stabilised in the full-length ABC transporter.

Structural Biology
🧩

Protein Folding & Proteostasis Research

F508del-CFTR is the archetypal misfolded membrane protein. Tezacaftor serves as a model pharmacological chaperone for studying ER quality control, ERAD, chaperone networks (HSP70, HSP90, calnexin) and the general principle of small-molecule proteostasis correction.

Proteostasis
💧

Epithelial Ion Transport & Electrophysiology

Central to Ussing chamber short-circuit current measurements in air-liquid interface primary human bronchial epithelial (HBE) cultures, patch clamp recordings, halide-sensitive YFP quenching assays and airway surface liquid height and pH measurements.

Electrophysiology
🦠

Patient-Derived Organoid Theratyping

The forskolin-induced swelling (FIS) assay in rectal and intestinal organoids from individual patients uses tezacaftor-containing combinations to predict personal clinical response, extending modulator access to rare genotypes not covered by registration trials.

Precision Medicine
🧦

CFTR Modulator Combination Pharmacology

Used to dissect synergy with the potentiator ivacaftor and additivity with the second-site corrector elexacaftor (VX-445). Essential for isobologram and Bliss-independence analysis of dual and triple modulator regimens and for mapping non-overlapping corrector mechanisms.

Combination Therapy
🥚

Rare & Residual-Function Mutation Studies

Beyond F508del, tezacaftor/ivacaftor activity has been characterised across residual-function alleles including R117H, D1152H, A455E, P67L, S945L and 3849+10kbC→T, supporting genotype-specific mechanistic work and in vitro theratyping panels.

Genotype Coverage
📊

ADME, DDI & Pharmacokinetic Research

Unlike lumacaftor, tezacaftor is not a strong CYP3A inducer, making it a valuable comparator in drug-drug interaction studies. Also used in microsomal stability, hepatocyte metabolism, transporter interaction and metabolite identification (M1-TEZ) workflows.

DMPK
💉

Formulation & Analytical Method Development

Low aqueous solubility makes tezacaftor a practical model for amorphous solid dispersion, spray-dried dispersion, nanosuspension and co-crystal research, and it serves as a reference standard for UPLC-MS/MS bioanalytical method validation.

Formulation Science

Key Publications on Tezacaftor & CFTR Modulation

Pivotal mechanistic papers and registration trials defining the corrector-potentiator paradigm in cystic fibrosis

Taylor-Cousar JL, Munck A, McKone EF, et al. Tezacaftor-ivacaftor in patients with cystic fibrosis homozygous for Phe508del (EVOLVE). New England Journal of Medicine. 2017;377(21):2013-2023.
doi: 10.1056/NEJMoa1709846
Rowe SM, Daines C, Ringshausen FC, et al. Tezacaftor-ivacaftor in residual-function heterozygotes with cystic fibrosis (EXPAND). New England Journal of Medicine. 2017;377(21):2024-2035.
doi: 10.1056/NEJMoa1709847
Middleton PG, Mall MA, Dřevínek P, et al. Elexacaftor-tezacaftor-ivacaftor for cystic fibrosis with a single Phe508del allele. New England Journal of Medicine. 2019;381(19):1809-1819.
doi: 10.1056/NEJMoa1908639
Van Goor F, Hadida S, Grootenhuis PDJ, et al. Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809. Proceedings of the National Academy of Sciences USA. 2011;108(46):18843-18848.
doi: 10.1073/pnas.1105787108
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. Journal of Cystic Fibrosis. 2014;13(1):29-36.
doi: 10.1016/j.jcf.2013.06.008
Keating D, Marigowda G, Burr L, et al. VX-445-tezacaftor-ivacaftor in patients with cystic fibrosis and one or two Phe508del alleles. New England Journal of Medicine. 2018;379(17):1612-1620.
doi: 10.1056/NEJMoa1807120
Fiedorczuk K, Chen J. Mechanism of CFTR correction by type I folding correctors. Cell. 2022;185(1):158-168.e11.
doi: 10.1016/j.cell.2021.12.009

Tezacaftor Pack Sizes & Ordering Information

Research-grade Tezacaftor / VX-661 (CAS 1152311-62-0) supplied in 1g / 5g / 10g / 100g / 1KG with full QC documentation; custom bulk quantities supported

TierPack SizeStock StatusSuitable ForShipping & Lead Time
Standard1 gIn StockHBE and organoid correction assays, YFP quenching, Western blot band C analysisCold-chain or ambient with ice pack; same/next-day dispatch
Medium5 gIn StockUssing chamber programmes, dose-response matrices, combination pharmacologyCold-chain shipping; same/next-day dispatch
Large10 gIn StockIn vivo PK studies, multi-site consortia, HTS confirmation setsCold-chain shipping; same/next-day dispatch
Bulk100 gIn StockFormulation and solid dispersion development, toxicology batches, analytical standardsInsulated carton with COA; quote to confirm dispatch
Industrial1 KGMade to orderPilot and production scale, CMO/CDMO supply, process validation campaignsDrum shipment with batch COA; scheduled batch delivery

💡 Reference pack sizes shown above; for exact pricing, lot availability and bulk tezacaftor supply please contact us for a quote. Tiered discounts apply to bulk orders.

Tezacaftor FAQ — Frequently Asked Questions

Common technical and scientific questions about VX-661 pharmacology, assay design, handling and sourcing

What is Tezacaftor (VX-661, CAS 1152311-62-0)?
Tezacaftor is a second-generation CFTR corrector developed by Vertex Pharmaceuticals (C26H27F3N2O6, MW 520.50). It is a small-molecule pharmacological chaperone that binds nascent mutant CFTR and improves its folding and trafficking to the epithelial apical membrane. Approved in 2018 in combination with ivacaftor as SYMDEKO® (SYMKEVI® in Europe), it is also one of three actives in the triple combination TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor), which transformed cystic fibrosis care by extending effective treatment to roughly 90% of people with CF.
Corrector vs potentiator — what is the fundamental difference?
A corrector (tezacaftor, lumacaftor, elexacaftor) works on protein quantity: it stabilises folding so more CFTR escapes ER degradation and reaches the cell surface. A potentiator (ivacaftor) works on channel quality: it binds CFTR already at the membrane and increases open probability so more chloride passes per channel per second. F508del-CFTR suffers from both a trafficking defect and a gating defect, which is precisely why corrector monotherapy gives only modest benefit and why corrector-plus-potentiator combinations are the therapeutic standard.
Tezacaftor vs lumacaftor (VX-809) — which should I use?
Both are type I / site-1 correctors that share the N-aryl-1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropanecarboxamide scaffold and both stabilise MSD1. The decisive differences are pharmacological rather than mechanistic: lumacaftor is a strong CYP3A4 inducer that markedly reduces ivacaftor exposure and creates extensive drug-drug interactions, and it is associated with a higher rate of chest tightness and dyspnoea. Tezacaftor is not a significant CYP3A inducer and is better tolerated. For pure in vitro mechanism-of-correction work either is acceptable, but tezacaftor is the more clinically relevant choice and the standard comparator in modern CF studies.
What exactly is the F508del mutation?
F508del is an in-frame three-base-pair deletion removing phenylalanine at position 508 within nucleotide-binding domain 1 (NBD1) of CFTR. It is present on at least one allele in approximately 85-90% of people with cystic fibrosis, making it by far the most common CF-causing variant. The deletion has two consequences: NBD1 itself is thermally destabilised, and the NBD1–MSD1 and NBD1–NBD2 domain interfaces fail to assemble. ER quality control detects the misfolded protein and routes it to proteasomal degradation, so almost no channel reaches the surface. It is classified as a Class II (processing/trafficking) mutation.
Why is triple combination therapy so much more effective?
Because the three agents address three separate defects at three distinct binding sites. Tezacaftor stabilises MSD1 (site 1), elexacaftor binds a different, non-overlapping site and provides additive correction, and ivacaftor potentiates gating of whatever channel reaches the membrane. Dual tezacaftor/ivacaftor gave roughly a 4 percentage-point improvement in percent-predicted FEV1 in F508del homozygotes (EVOLVE), whereas the triple combination delivered approximately a 13.8 percentage-point improvement in F508del/minimal-function patients (Middleton et al., NEJM 2019) with a sweat chloride reduction exceeding 40 mmol/L.
How do I prepare tezacaftor stock solutions and what concentration should I use?
Tezacaftor dissolves in DMSO at approximately 21 mg/mL (sonication assists) and is insoluble in ethanol. Prepare a 10-20 mM DMSO stock, aliquot into single-use tubes and store at -20°C (6 months) or -80°C (1 year). Keep the final DMSO in culture at or below 0.1% v/v. Typical correction protocols use 1-10 µM for 18-48 hours before functional readout — correction is not instantaneous because it requires a cycle of new protein synthesis, folding, trafficking and glycosylation. Always include a DMSO vehicle control and, ideally, an acute ivacaftor potentiation step at readout.
Which assays best demonstrate tezacaftor-mediated CFTR correction?
The most informative are: Ussing chamber short-circuit current (Isc) in primary human bronchial epithelial cells at air-liquid interface, which is the gold standard; forskolin-induced swelling (FIS) in patient-derived rectal or intestinal organoids for personalised theratyping; halide-sensitive YFP quenching for higher-throughput screening; and patch clamp for single-channel behaviour. Biochemically, correction is quantified by the band C to band B ratio on Western blot (complex-glycosylated mature CFTR versus core-glycosylated immature CFTR) and by cell-surface biotinylation or confocal immunofluorescence.
Does tezacaftor work on mutations other than F508del?
Yes, though F508del is the primary target. In combination with ivacaftor, tezacaftor is active in patients heterozygous for F508del plus a residual-function allele, including R117H, D1152H, R347H, A455E, P67L, S945L, R1070W and the splice variant 3849+10kbC→T — the population studied in the EXPAND trial. When paired with elexacaftor in the triple regimen, benefit extends to F508del heterozygotes carrying minimal-function mutations, which previously had no modulator option. It has no expected activity in Class I nonsense mutations such as G542X, which require read-through or gene-based approaches.
What are the storage and stability requirements?
Supply the powder at 2-8°C, sealed and protected from light; some suppliers recommend storage under nitrogen at -20°C for extended periods. Under these conditions the solid is stable for at least two years. DMSO stock solutions should be aliquoted and held at -20°C for up to 6 months or -80°C for up to 1 year; avoid repeated freeze-thaw cycles, which promote precipitation and apparent loss of potency. Allow vials to equilibrate to room temperature before opening to prevent moisture condensation.
What purity, documentation and pack sizes are available?
Research-grade tezacaftor is supplied at ≥98% purity by HPLC with ≥99% ee at the single defined stereocentre. Each batch ships with a Certificate of Analysis covering HPLC purity, 1H and 19F NMR, LC-MS, chiral HPLC, Karl Fischer water content and appearance. Pack sizes of 1 g, 5 g, 10 g and 100 g are in stock with 1 KG produced made-to-order. MSDS/SDS, residual solvent data and Certificates of Origin are available on request — contact us for pricing or custom specifications.

Need Tezacaftor (VX-661) for Your CFTR Research?

Research-grade Tezacaftor (CAS 1152311-62-0) — C26H27F3N2O6, MW 520.50, purity ≥98% HPLC, COA included
The reference F508del CFTR corrector for cystic fibrosis research — available 1g to 1KG

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Weight 1 g

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