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.
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2D Structure
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Physico-chemical Properties
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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
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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)
1. Zhu Y, Ye X, Shen H, Li J, Cai Z, Min W, Hou W, Dong H, Wu Y, Wang L et al.. (2023)
Discovery of Novel Fourth-Generation EGFR Inhibitors to Overcome C797S-Mediated Resistance.
J Med Chem, [Epub ahead of print]. DOI: 10.1021/acs.jmedchem.3c01165