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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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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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
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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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
InChI Key USHQRIKZLHNPQR-JTQLQIEISA-N
No information available.
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