pebezertinib   Click here for help

GtoPdb Ligand ID: 13064

Synonyms: BLU-451 | BLU451 | compound I [WO2023215431A1] [3] | Example 37 [WO2022094354A1] [4] | LNG-451 | LNG451
Compound class: Synthetic organic
Comment: Although the name-to-structure for BLU-451 has not been formally published, a focussed review of patents [3-4], declared company pipelines (Blueprint Medicines [1]), published literature, meeting abstracts [6] and other online information leads us to consider the chemical structure presented here as a very strong candidate for BLU-451.

BLU-451 (formerly LNG-451) is a wild-type EGFR-sparing, CNS-penetrant and covalent EGFR Exon 20 insertion (Ex20ins) inhibitor that is in development for anti‑tumour potential, particularly for non-small cell lung cancers that express variant EGFRs with Exon 20 insertions (i.e., resistance mutations) [2,5]. The Ex20ins-targeting drugs amivantamab and mobocertinib are already in clinical use, but their activity within the brain has not been established. Minimising activity at WT EGFRs is propsed to reduce on-target toxicity.

The chemical structure for BLU-451 was matched to that for the INN pebezertinib from WHO proposed INN list 131 (August 2024).

pebezertinib 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 8
Hydrogen bond donors 3
Rotatable bonds 9
Topological polar surface area 93.48
Molecular weight 497.45
XLogP 2.21
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)NC1=CC=C(C(=C1)NC2=C(C=NC(=N2)NC3=CN(C)N=C3)C4=CC=C(C=C4)C(F)(F)F)F
Isomeric SMILES CN1C=C(NC2=NC=C(C(NC3=C(F)C=CC(NC(=O)C=C)=C3)=N2)C4=CC=C(C=C4)C(F)(F)F)C=N1
InChI InChI=1S/C24H19F4N7O/c1-3-21(36)31-16-8-9-19(25)20(10-16)33-22-18(14-4-6-15(7-5-14)24(26,27)28)12-29-23(34-22)32-17-11-30-35(2)13-17/h3-13H,1H2,2H3,(H,31,36)(H2,29,32,33,34)
InChI Key XIMJCWSFLXXQMZ-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/)
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Canonical SMILES Download
Isomeric SMILES Download
InChI standard identifier Download
InChI standard key Download

Molecular structure representations generated using Open Babel