icenticaftor   Click here for help

GtoPdb Ligand ID: 11547

Synonyms: compound 33 [PMID: 34028270] | QBW-251 | QBW251
Compound class: Synthetic organic
Comment: Icenticaftor (QBW251) is a compound that potentiates/improves transport of chloride ions via mutant cystic fibrosis transmembrane conductance regulator (CFTR) ion channels [1]. It is a clinical lead for cystic fibrosis and chronic obstructive pulmonary disease (COPD) [2], having demonstrated clinical proofs of concept in both conditions. In patients with CF it induced significant clinical benefit in those with Class III and IV CFTR mutations. Class III and IV mutations are those which impair gating or conductance of the channel respectively [3]. The potentiator ivacaftor is aleady approved to restore function in channels with class III mutations, but at the time of writing (May 2021) there was no approved potentiator for class IV mutant channels.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 3
Rotatable bonds 7
Topological polar surface area 97.47
Molecular weight 361.09
XLogP 2.61
No. Lipinski's rules broken 0
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Canonical SMILES COc1nc(C(=O)NC[C@@](C(F)(F)F)(O)C)c(cc1C(F)(F)F)N
Isomeric SMILES COc1nc(C(=O)NC[C@@](C(F)(F)F)(O)C)c(cc1C(F)(F)F)N
InChI InChI=1S/C12H13F6N3O3/c1-10(23,12(16,17)18)4-20-8(22)7-6(19)3-5(11(13,14)15)9(21-7)24-2/h3,23H,4,19H2,1-2H3,(H,20,22)/t10-/m0/s1
Selectivity at ion channels
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
CFTR Hs None Potentiation 7.3 pEC50 - 1
pEC50 7.3 (EC50 4.7x10-8 M) [1]
Description: Current determined in CHO cells stably expressing the delF508-CFTR channel.