Peer-reviewedCC BY-NCAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Functional and biochemical characterization of Alyftrek® components reveals high-potency rescue of F508del-CFTR
Abstract
Alyftrek (vanzacaftor/tezacaftor/deutivacaftor) was evaluated in cystic fibrosis (CF) airway models. S-vanzacaftor showed high potency, restoring F508del-CFTR function at nanomolar concentrations, enhanced by tezacaftor. Deutivacaftor matched ivacaftor efficacy in triple combinations. Both regimens improved CFTR maturation. The R-enantiomer was less effective and antagonistic. Notably, reduced doses retained substantial activity, supporting lower dosing strategies. These findings highlight S-vanzacaftor potency and validate deutivacaftor as an effective potentiator in CF therapy.
Related
- Genetic, biochemical, and structural characterization of a novel KLUS subgroup of CTX-M-type extended-spectrum β-lactamases reveals an evolutionarily distinct lineage with unique functional properties
- Evolutionary and Functional Characterization of the Allene Oxide Cyclase (AOC) Gene Family Reveals the Joint Contribution of GhAOC4/6 to Cotton Resistance Against Verticillium dahliae
- Functional characterization of the 26RFa/orexin neurons of the lateral hypothalamic area reveals their key role in the control of glucose homeostasis
- Functional Characterization of ClHSP22.9 Promoter from Wild Watermelon (Citrullus lanatus) Reveals Heat- and Drought-Inducible Transcriptional Activity
- Functional characterization of TaSnRK2.8-5A reveals the central role of its signal module in enhancing drought tolerance through coordinated molecular and physiological response of wheat
BibTeX
@article{mirval2026functional,
title = {{Functional and biochemical characterization of Alyftrek® components reveals high-potency rescue of F508del-CFTR}},
author = {Sandra Mirval and Louise Damy and Auguste Sauvage de Gérando and Christine Barrault and Isabelle Fixe and Édouard Sage and Christelle Coraux and Benjamin Simonneau and Benedicte Duriez and Pascale Fanen and Anne Cantereau and Clarisse Vandebrouck and Frederic Becq},
journal = {American Journal of Physiology - Lung Cellular and Molecular Physiology},
year = {2026},
month = aug,
doi = {10.1152/ajplung.00103.2026},
url = {https://univ-reims.hal.science/hal-05743413v1},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Functional and biochemical characterization of Alyftrek® components reveals high-potency rescue of F508del-CFTR
AU - Sandra Mirval
AU - Louise Damy
AU - Auguste Sauvage de Gérando
AU - Christine Barrault
AU - Isabelle Fixe
AU - Édouard Sage
AU - Christelle Coraux
AU - Benjamin Simonneau
AU - Benedicte Duriez
AU - Pascale Fanen
AU - Anne Cantereau
AU - Clarisse Vandebrouck
AU - Frederic Becq
PY - 2026
DA - 2026/08/19
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
DO - 10.1152/ajplung.00103.2026
UR - https://univ-reims.hal.science/hal-05743413v1
AB - Alyftrek (vanzacaftor/tezacaftor/deutivacaftor) was evaluated in cystic fibrosis (CF) airway models. S-vanzacaftor showed high potency, restoring F508del-CFTR function at nanomolar concentrations, enhanced by tezacaftor. Deutivacaftor matched ivacaftor efficacy in triple combinations. Both regimens improved CFTR maturation. The R-enantiomer was less effective and antagonistic. Notably, reduced doses retained substantial activity, supporting lower dosing strategies. These findings highlight S-vanzacaftor potency and validate deutivacaftor as an effective potentiator in CF therapy.
SN - 1040-0605
SN - 1522-1504
ER -