dosimertinib   Click here for help

GtoPdb Ligand ID: 12710

Synonyms: compound 2h [PMID: 33459024]
Compound class: Synthetic organic
Comment: Dosimertinib is a deuterated analogue of the EGFR tyrosine kinase inhibitor osimertinib [1]. It was designed for potential to treat advanced EGFR mutation-positive non-small-cell lung cancer.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 9
Hydrogen bond donors 2
Rotatable bonds 11
Topological polar surface area 84.8
Molecular weight 499.61
XLogP 2.3
No. Lipinski's rules broken 0
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Canonical SMILES C([2H])([2H])=CC(=O)NC1=C(C=C(C(=C1)NC2=NC=CC(=N2)C3=CN(C([2H])([2H])[2H])C4=C3C=CC=C4)OC)N(C)CCN(C)C
Isomeric SMILES O=C(C=C([2H])[2H])NC1=CC(NC2=NC(C3=CN(C4=C3C=CC=C4)C([2H])([2H])[2H])=CC=N2)=C(OC)C=C1N(CCN(C)C)C
InChI InChI=1S/C28H33N7O2/c1-7-27(36)30-22-16-23(26(37-6)17-25(22)34(4)15-14-33(2)3)32-28-29-13-12-21(31-28)20-18-35(5)24-11-9-8-10-19(20)24/h7-13,16-18H,1,14-15H2,2-6H3,(H,30,36)(H,29,31,32)/i1D2,5D3
Bioactivity Comments
Inhibitor potency is likely to be very similar to the parent osimertinib. Deuteration extends in vivo half-life and blocks formation of a metabolite of osimertinib (AZ5104) that is associated with drug toxicity.
Selectivity at catalytic receptors
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
epidermal growth factor receptor Hs Inhibitor Inhibition 6.9 – 8.8 pIC50 - 1
pIC50 8.8 (IC50 1.7x10-9 M) [1]
Description: Enzymatic inhibitory activity vs. L858R/T790M EGFR
pIC50 6.9 (IC50 1.138x10-7 M) [1]
Description: Enzymatic inhibitory activity vs. WT EGFR