C34 [Zhu et al., 2023]   Click here for help

GtoPdb Ligand ID: 12981

Compound class: Synthetic organic
Comment: C34 is a fourth generation EGFR inhibitor that is designed to overcome EGFRC797S mutation-mediated resistance to third-generation irreversible inhibitors such as osimertinib [1]. The C797S mutation negates the ability of the acrylamide warhead of osimertinib to form its covalent bond with Cys797 and this leads to severely diminished therapeutic efficacy.
Click here for help
2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
Hydrogen bond acceptors 9
Hydrogen bond donors 1
Rotatable bonds 10
Topological polar surface area 126.65
Molecular weight 633.81
XLogP 1.89
No. Lipinski's rules broken 1
Click here for help
Canonical SMILES CCS(=O)(=O)N1CCC(CC1)C2=NC(=C(C3=NC(=NC=C3)NC4=CC5=C(C=C4)N(C=C5)CCN(C)C)S2)C6=CC=C(C=C6)F
Isomeric SMILES FC1=CC=C(C2=C(C3=CC=NC(NC4=CC=C5N(CCN(C)C)C=CC5=C4)=N3)SC(C6CCN(S(=O)(CC)=O)CC6)=N2)C=C1
InChI InChI=1S/C32H36FN7O2S2/c1-4-44(41,42)40-17-13-23(14-18-40)31-37-29(22-5-7-25(33)8-6-22)30(43-31)27-11-15-34-32(36-27)35-26-9-10-28-24(21-26)12-16-39(28)20-19-38(2)3/h5-12,15-16,21,23H,4,13-14,17-20H2,1-3H3,(H,34,35,36)
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 7.0 – 8.3 pIC50 - 1
pIC50 8.3 (IC50 5.1x10-9 M) [1]
Description: Inhibition of EGFR triple mutant L858R/T790M/C797S
pIC50 7.0 (IC50 1.06x10-7 M) [1]
Description: Inhibition of wild type hEGFR