zorifertinib   Click here for help

GtoPdb Ligand ID: 10456

Synonyms: AZD-3759 | AZD3759 | compound 1m [PMID: 26313252]
Compound class: Synthetic organic
Comment: Zorifertinib (AZD3759) is an investigational EGFR tyrosine kinase inhibitor [1]. It is potent, orally active and brain-penetrant. AZD3759 was designed to target brain metastases in patients with advanced EGFR-driven lung cancer.
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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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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 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 6
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 79.82
Molecular weight 459.15
XLogP 3.12
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 COc1cc2ncnc(c2cc1OC(=O)N1CCN(CC1C)C)Nc1cccc(c1F)Cl
Isomeric SMILES COc1cc2ncnc(c2cc1OC(=O)N1CCN(C[C@H]1C)C)Nc1cccc(c1F)Cl
InChI InChI=1S/C22H23ClFN5O3/c1-13-11-28(2)7-8-29(13)22(30)32-19-9-14-17(10-18(19)31-3)25-12-26-21(14)27-16-6-4-5-15(23)20(16)24/h4-6,9-10,12-13H,7-8,11H2,1-3H3,(H,25,26,27)/t13-/m1/s1
InChI Key MXDSJQHFFDGFDK-CYBMUJFWSA-N
Bioactivity Comments
Potential off-targets identified in a target screening panel (IC50 values in parentheses) were KDR (156 nM), Src (622 nM), and D2 (797 nM) [1].
Selectivity at ion channels
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
Kv11.1 Hs Inhibitor Inhibition 4.9 pIC50 - 1
⤷ pIC50 4.9 (IC50 1.33x10-5 M) [1]
Description: Channel inhibition measured in a conventional manual whole-cell patch clamp study.
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 Primary target of this compound Hs Inhibitor Inhibition 8.1 – 9.5 pIC50 - 1
⤷ pIC50 9.5 (IC50 3x10-10 M) [1]
Description: Inhibition of wild type EGFR in vitro, at Km of ATP.
pIC50 8.1 (IC50 7.2x10-9 M) [1]
Description: Inhibition of EGFRL858R in vitro.