ceritinib   Click here for help

GtoPdb Ligand ID: 7397

Synonyms: compound 15b [PMID 23742252] | LDK378 | NVP-LDK378-NX | Zykadia®
Approved drug PDB Ligand
ceritinib is an approved drug (FDA (2014), EMA (2015))
Compound class: Synthetic organic
Comment: Ceritinib is a novel, highly selective, second generation ALK inhibitor [2].
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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: ceritinib

ceritinib is commercially available from our sponsors

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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 7
Hydrogen bond donors 3
Rotatable bonds 9
Topological polar surface area 113.62
Molecular weight 557.22
XLogP 6.55
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES CC(Oc1cc(C2CCNCC2)c(cc1Nc1ncc(c(n1)Nc1ccccc1S(=O)(=O)C(C)C)Cl)C)C
Isomeric SMILES CC(Oc1cc(C2CCNCC2)c(cc1Nc1ncc(c(n1)Nc1ccccc1S(=O)(=O)C(C)C)Cl)C)C
InChI InChI=1S/C28H36ClN5O3S/c1-17(2)37-25-15-21(20-10-12-30-13-11-20)19(5)14-24(25)33-28-31-16-22(29)27(34-28)32-23-8-6-7-9-26(23)38(35,36)18(3)4/h6-9,14-18,20,30H,10-13H2,1-5H3,(H2,31,32,33,34)
InChI Key VERWOWGGCGHDQE-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Oroginally approved for the treatment of patients with non-small cell lung cancer with activating rearrangements in their ALK (anaplastic lymphoma kinase) gene (aka ALK +ve NSCLC), who have previously been treated with crizotinib and in whom drug resistance has developed [3]. In May 2017, approval was expanded to cover all patients with ALK+ve NSCLC, including previously untreated patients.
A list of clinical trials involving this drug, under its research code LDK378, is available at ClinicalTrials.gov.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase of the insulin receptor superfamily. Ceritinib inhibits the activity of ALK in cancers driven by activating ALK gene rearrangements [2-3]. The drug discovery article by Marsilje et al (2014) reviews the types of activating ALK mutations so far identified in different neoplasms. Ceritinib (compound 15b in the article) has been designed to posess superior ALK selectivity and appears to be able to overcome the problem of crizotinib resistance, which may be caused by aquired mutation in the gatekeeper residue protecting the kinase ATP binding pocket (explanation of possible mechanisms in [4] and [1]). ALK selectivity is apparent across a large panel of tested kinases, with ceritinib having an IC50 of 0.2nM for ALK [2].
Pharmacokinetics Click here for help
Absorption/Distribution
Cmax is achieved approximately 6 hours after dosing, with steady-state drug level achieved by approximately day 15 [3].
Biotransformation/Metabolism
Terminal half-life of ceritinib is approximately 40 hours [3].
Population pharmacokinetics
Not yet dertermined.
Organ function impairment
Not yet dertermined.
External links Click here for help
For extended ADME data see the following:

Drugs.com
European Medicines Agency (EMA)