lumacaftor   Click here for help

GtoPdb Ligand ID: 7481

Synonyms: VRT-826809 | VX-809 | VX809
Approved drug PDB Ligand
lumacaftor is an approved drug (EMA & FDA (2015))
Compound class: Synthetic organic
Comment: Lumacaftor is termed a cystic fibrosis transmembrane conductance regulator (CFTR) corrector, acting to reduce mis-folding of the defective F508del mutant CFTR protein, in comparison to ivacaftor which is termed a CFTR potentiator drug. The F508del mutation is the most common cause of cystic fibrosis and accounts for approximately 60% of CF patients in Europe. Cryo-electron microscopy of CFTR-lumacaftor complexes provided insight into how the correctors operate at the molecular level, with the findings published in early 2022 by Fiedorczuk and Chen [1].
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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

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View more information in the IUPHAR Pharmacology Education Project: lumacaftor

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 2
Rotatable bonds 6
Topological polar surface area 97.75
Molecular weight 452.12
XLogP 4.93
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 O=C(C1(CC1)c1ccc2c(c1)OC(O2)(F)F)Nc1ccc(c(n1)c1cccc(c1)C(=O)O)C
Isomeric SMILES O=C(C1(CC1)c1ccc2c(c1)OC(O2)(F)F)Nc1ccc(c(n1)c1cccc(c1)C(=O)O)C
InChI InChI=1S/C24H18F2N2O5/c1-13-5-8-19(27-20(13)14-3-2-4-15(11-14)21(29)30)28-22(31)23(9-10-23)16-6-7-17-18(12-16)33-24(25,26)32-17/h2-8,11-12H,9-10H2,1H3,(H,29,30)(H,27,28,31)
InChI Key UFSKUSARDNFIRC-UHFFFAOYSA-N
References
1. Fiedorczuk K, Chen J. (2022)
Mechanism of CFTR correction by type I folding correctors.
Cell, 185 (1): 158-168.e11. [PMID:34995514]
2. Okiyoneda T, Veit G, Dekkers JF, Bagdany M, Soya N, Xu H, Roldan A, Verkman AS, Kurth M, Simon A et al.. (2013)
Mechanism-based corrector combination restores ΔF508-CFTR folding and function.
Nat Chem Biol, 9 (7): 444-54. [PMID:23666117]
3. Pesci E, Bettinetti L, Fanti P, Galietta LJ, La Rosa S, Magnoni L, Pedemonte N, Sardone GL, Maccari L. (2015)
Novel Hits in the Correction of ΔF508-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Protein: Synthesis, Pharmacological, and ADME Evaluation of Tetrahydropyrido[4,3-d]pyrimidines for the Potential Treatment of Cystic Fibrosis.
J Med Chem, 58 (24): 9697-711. [PMID:26561003]
4. Ren HY, Grove DE, De La Rosa O, Houck SA, Sopha P, Van Goor F, Hoffman BJ, Cyr DM. (2013)
VX-809 corrects folding defects in cystic fibrosis transmembrane conductance regulator protein through action on membrane-spanning domain 1.
Mol Biol Cell, 24 (19): 3016-24. [PMID:23924900]