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
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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
Bioactivity Comments
Elevation of CFTR protein on the surface of patient-derived bronchial epithelial cells (with either the F508del-MF genotype, or the F508del-F508del genotype) in the presence of elexacaftor was determined using immuno-staining [3].
Selectivity at ion channels
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
CFTR Hs None Binding 7.2 pEC50 - 1,3
pEC50 7.2 (EC50 7x10-8 M) [1,3]