xiliertinib   Click here for help

GtoPdb Ligand ID: 9929

Synonyms: HMPL-309 | HMPL309 | theliatinib
Compound class: Synthetic organic
Comment: Xiliertinib (HMPL-309) is an ATP-competitive EGFR tyrosine kinase inhibitor that was developed for anticancer potential [1].
Theliatinib appears to be a 'pseudo' INN, that uses the -tinib INN stem for tyrosine kinase inhibitors, but was not submitted to the World Health Organisation for ratification.
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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 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 2
Rotatable bonds 6
Topological polar surface area 81.56
Molecular weight 444.23
XLogP 1.4
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#Cc1cccc(c1)NC1N=CN=C2C1C=C(NC(=O)N1CC3C(C1)CCN3C)C(=C2)OC
Isomeric SMILES C#Cc1cccc(c1)NC1N=CN=C2C1C=C(NC(=O)N1C[C@H]3[C@@H](C1)CCN3C)C(=C2)OC
InChI InChI=1S/C25H28N6O2/c1-4-16-6-5-7-18(10-16)28-24-19-11-21(23(33-3)12-20(19)26-15-27-24)29-25(32)31-13-17-8-9-30(2)22(17)14-31/h1,5-7,10-12,15,17,19,22,24,28H,8-9,13-14H2,2-3H3,(H,29,32)/t17-,19?,22+,24?/m1/s1
InChI Key HJXSISWJKLMCHI-FIFRQSLGSA-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
Theliatinib exhibits anti-tumor efficacy in patient-derived xenograft models of esophageal cancers in which the EGFR gene is amplified or overexpressed [1]. It shows markedly greater potency than erlotinib or gefitinib at the enzyme and cell levels. Theliatinib inhibits the EGFRT790M/L858R mutant with an IC50 of 22nM (wild type IC50 is 3 nM).
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
LCK proto-oncogene, Src family tyrosine kinase Hs Inhibitor Inhibition 6.8 pIC50 - 1
⤷ pIC50 6.8 (IC50 1.76x10-7 M) [1]
tyrosine kinase non receptor 1 Hs Inhibitor Inhibition 6.6 pIC50 - 1
⤷ pIC50 6.6 (IC50 2.56x10-7 M) [1]
YES proto-oncogene 1, Src family tyrosine kinase Hs Inhibitor Inhibition 6.5 pIC50 - 1
⤷ pIC50 6.5 (IC50 3.34x10-7 M) [1]
LYN proto-oncogene, Src family tyrosine kinase Hs Inhibitor Inhibition 6.3 pIC50 - 1
⤷ pIC50 6.3 (IC50 5.01x10-7 M) [1]
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 10.3 pKi - 1
⤷ pKi 10.3 (Ki 5x10-11 M) [1]
erb-b2 receptor tyrosine kinase 4 Hs Inhibitor Inhibition 6.2 pIC50 - 1
⤷ pIC50 6.2 (IC50 7.05x10-7 M) [1]