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
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Summary of Clinical Use Click here for help
Acquired CFTR dysfunction (e.g. induced by cigarette smoke) may contribute to the pathophysiology of COPD, and improving the defective conductance using CFTR potentiators is expected to provide clinical benefit. Icenticaftor (QBW251) has advanced to mid-stage clinical evaluation in patients with COPD.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02190604 Safety, Tolerability, Pharmacokinetics, and Preliminary Pharmacodynamics of QBW251 in Healthy Subjects and Cystic Fibrosis Patients Phase 1/Phase 2 Interventional Novartis 2
NCT04268823 Clinical Study to Assess the Mode of Action of QBW251 in Patients With Chronic Obstructive Pulmonary Disease (COPD) Phase 2 Interventional Novartis
NCT04072887 Dose-range Finding Efficacy and Safety Study for QBW251 in COPD Patients Phase 2 Interventional Novartis
NCT02449018 A Safety, Tolerability and Efficacy Study With QBW251 in COPD Patients With QBW251 Phase 2 Interventional Novartis