allitinib   Click here for help

GtoPdb Ligand ID: 9912

Synonyms: ALL-3 | AST-1306 | AST1306
Compound class: Synthetic organic
Comment: Allitinib (AST-1306) is an irreversible inhibitor of the wild-type epidermal growth factor receptor (EGFR) and ErbB2 (HER2) [1]. It also inhibits the mutant EGFRT790M/L858R. Allitinib was designed by Allist Pharmaceuticals to overcome acquired resistance to EGFR inhibitor therapy. It is active in vitro and in vivo.
Allitinib is a 'pseudo' INN, that takes the form of an INN, but has not been submitted to the World Health Organisation for ratification.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 76.14
Molecular weight 448.11
XLogP 4.98
No. Lipinski's rules broken 0
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Canonical SMILES C=CC(=O)Nc1ccc2c(c1)c(ncn2)Nc1ccc(c(c1)Cl)OCc1cccc(c1)F
Isomeric SMILES C=CC(=O)Nc1ccc2c(c1)c(ncn2)Nc1ccc(c(c1)Cl)OCc1cccc(c1)F
InChI InChI=1S/C24H18ClFN4O2/c1-2-23(31)29-17-6-8-21-19(11-17)24(28-14-27-21)30-18-7-9-22(20(25)12-18)32-13-15-4-3-5-16(26)10-15/h2-12,14H,1,13H2,(H,29,31)(H,27,28,30)
Bioactivity Comments
Allitinib (AST-1306) inhibits the EGFR carrying the dual T790M/L858R mutation with an in vitro IC50 of 12 nM [1]. The growth-inhibitory effects of AST-1306 are more potent in ErbB2-overexpressing cells compared to EGFR-overexpressing cells.
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 9.3 pIC50 - 1
pIC50 9.3 (IC50 5x10-10 M) [1]
erb-b2 receptor tyrosine kinase 4 Hs Inhibitor Inhibition 9.1 pIC50 - 1
pIC50 9.1 (IC50 8x10-10 M) [1]
erb-b2 receptor tyrosine kinase 2 Hs Inhibitor Inhibition 8.5 pIC50 - 1
pIC50 8.5 (IC50 3x10-9 M) [1]