lazertinib   Click here for help

GtoPdb Ligand ID: 10136

Synonyms: Compound 73 [WO2016060443A2] | GNS-1480 | GNS1480 | Lazcluze® | Leclaza® | YH-25448 | YH25448
Approved drug
lazertinib is an approved drug (S. Korea (2021), FDA (2024))
Compound class: Synthetic organic
Comment: Lazertinib (YH-25448, GNS-1480) is an oral, third-generation inhibitor of the aberrant activity of mutant EGFR kinases (EGFR T790M and the activating EGFR mutations Ex19del and L858R), that was originally developed by Yuhan Corporation for antineoplastic potential in cancers with (acquired) resistance to existing EGFR tyrosine kinase inhibitors [1], in particular for EGFR mutation positive, advanced non-small cell lung cancer (NSCLC). It is claimed in Yuhan's patent WO2016060443A2 as compound 73 [1].
In addition to predicted efficacy for the treatment of primary lung and extracranial lesions, lazertinib is expected to be beneficial for NSCLC brain metastases as it is able to cross the blood brain barrier.
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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

lazertinib 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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Click here for structure editor
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 9
Hydrogen bond donors 2
Rotatable bonds 11
Topological polar surface area 109.15
Molecular weight 554.28
XLogP 3.49
No. Lipinski's rules broken 0

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 C=CC(=O)Nc1cc(Nc2nccc(n2)n2cc(c(n2)c2ccccc2)CN(C)C)c(cc1N1CCOCC1)OC
Isomeric SMILES C=CC(=O)Nc1cc(Nc2nccc(n2)n2cc(c(n2)c2ccccc2)CN(C)C)c(cc1N1CCOCC1)OC
InChI InChI=1S/C30H34N8O3/c1-5-28(39)32-23-17-24(26(40-4)18-25(23)37-13-15-41-16-14-37)33-30-31-12-11-27(34-30)38-20-22(19-36(2)3)29(35-38)21-9-7-6-8-10-21/h5-12,17-18,20H,1,13-16,19H2,2-4H3,(H,32,39)(H,31,33,34)
InChI Key RRMJMHOQSALEJJ-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/)
Bioactivity Comments
The inhibitory potency of lazertinib vs. mutant EGFR (Del19, L858R, L858R/T790M and Del19/T790M mutants) in biochemical assays was determined to be <20 nM [1]. In cellular proliferation assays using PC9 and HI975 cancer cell lines, lazertinib was >200-fold selective for these mutant EGFR-containing cells compared to H2073 cells with wild type EGFRs. Lazertinib inhibits JAK3 with a biochemical IC50 of <20 nM, so this should be considered when analysing possible off-target effects.
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
Janus kinase 3 Hs Inhibitor Inhibition >7.7 pIC50 - 1
⤷ pIC50 >7.7 (IC50 <2x10-8 M) [1]
Description: In a biochemical enzyme activity assay.
spleen associated tyrosine kinase Hs Inhibitor Inhibition 6.0 – 6.7 pIC50 - 1
⤷ pIC50 6.0 – 6.7 (IC50 1x10-6 – 2.01x10-7 M) [1]
Description: In a biochemical enzyme activity assay.
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
epidermal growth factor receptor Hs Inhibitor Inhibition >7.7 pIC50 - 1
⤷ pIC50 >7.7 (IC50 <2x10-8 M) [1]
Description: Measuring inhibition of mutant EGFR kinase activities in biochemical assays (equivalent potency against Del19, L858R, L858R/T790M and Del19/T790M EGFR mutants). NOTE lazertinib is inactive vs. wild type EGFR.
kinase insert domain receptor Hs Inhibitor Inhibition <6.0 pIC50 - 1
⤷ pIC50 <6.0 (IC50 >1x10-6 M) [1]
Description: In a biochemical enzyme activity assay.