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
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Summary of Clinical Use Click here for help
Elexacaftor is approved as a component of a triple-combination therapy (Trikafta®) alongside ivacaftor (CFTR potentiator) and tezacaftor (CFTR corrector), as a treatment for cystic fibrosis. The combination of drugs increases both the number of correctly folded CFTR channels at the cell membrane (corrector function) and potentiates opening of the channels. These combined actions significantly restore chloride flow through the CFTR, which helps to correct salt and water balance at epithelial surfaces.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Like tezacaftor, elexacaftor is a CFTR corrector type agent. It helps to improve correct folding of the CFTR in the presence of the F508del mutation. This action increases the number of functional CFTR channels at the cell membrane which helps restore the salt/water balance at epithelial surfaces.