elexacaftor   Click here for help

GtoPdb Ligand ID: 10552

Synonyms: Compound 1 [WO2018107100A1] | VX-445
Approved drug
elexacaftor is an approved drug (FDA (2019))
Compound class: Synthetic organic
Comment: Elexacaftor (VX-445) is a next-generation CFTR corrector type agent. Like its predecessor tezacaftor, elexacaftor is designed to improve CFTR protein processing and trafficking in the presence of the F508del mutation, although because its mechanism of action is different from that of tezacaftor, its functional effects appear to be additive [3]. As such a triple combination therapeutic with tezacaftor, izacaftor (a CFTR potentiator that increases CFTR channel gating activity) and elexacaftor increases CFTR function beyond that achieved by current standard of care with tezacaftor/izacaftor, and improves clinical symptoms in patients with cystic fibrosis with one or two F508del alleles [2].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 8
Hydrogen bond donors 1
Rotatable bonds 10
Topological polar surface area 132.1
Molecular weight 597.23
XLogP 6.25
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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Canonical SMILES CC1CN(C(C1)(C)C)c1nc(ccc1C(=O)NS(=O)(=O)c1cn(nc1C)C)n1ccc(n1)OCC(C(F)(F)F)(C)C
Isomeric SMILES C[C@@H]1CN(C(C1)(C)C)c1nc(ccc1C(=O)NS(=O)(=O)c1cn(nc1C)C)n1ccc(n1)OCC(C(F)(F)F)(C)C
InChI InChI=1S/C26H34F3N7O4S/c1-16-12-25(5,6)35(13-16)22-18(23(37)33-41(38,39)19-14-34(7)31-17(19)2)8-9-20(30-22)36-11-10-21(32-36)40-15-24(3,4)26(27,28)29/h8-11,14,16H,12-13,15H2,1-7H3,(H,33,37)/t16-/m0/s1
InChI Key MVRHVFSOIWFBTE-INIZCTEOSA-N
References
1. Abela AR, Alcacio T, Anderson C, Angell PT, Baek M, Clemens JJ, Cleveland T, Ferris LA, Grootenhuis PDJ, Gross RS et al.. (2018)
Modulator of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator.
Patent number: WO2018107100A1. Assignee: Vertex Pharmaceuticals. Priority date: 09/12/2016. Publication date: 14/04/2019.
2. Heijerman HGM, McKone EF, Downey DG, Van Braeckel E, Rowe SM, Tullis E, Mall MA, Welter JJ, Ramsey BW, McKee CM et al.. (2019)
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, 394 (10212): 1940-1948. [PMID:31679946]
3. Keating D, Marigowda G, Burr L, Daines C, Mall MA, McKone EF, Ramsey BW, Rowe SM, Sass LA, Tullis E et al.. (2018)
VX-445-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles.
N Engl J Med, 379 (17): 1612-1620. [PMID:30334692]