JBJ-04-125-02   Click here for help

GtoPdb Ligand ID: 12982

PDB Ligand
Compound class: Synthetic organic
Comment: JBJ-04-125-02 is a fourth generation EGFR inhibitor [1]. It has an allosteric mode of action, and acts synergistically with the ATP-competitive inhibitor osimertinib.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 8
Hydrogen bond donors 3
Rotatable bonds 7
Topological polar surface area 122.57
Molecular weight 543.61
XLogP 0.85
No. Lipinski's rules broken 1
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Canonical SMILES C1=C(C=C2C(=C1)CN([C@H](C3=CC(=CC=C3O)F)C(=O)NC4=NC=CS4)C2=O)C5=CC=C(C=C5)N6CCNCC6
Isomeric SMILES C1CN(CCN1)C2=CC=C(C=C2)C3=CC4=C(CN(C4=O)[C@H](C5=C(C=CC(=C5)F)O)C(=O)NC6=NC=CS6)C=C3
InChI InChI=1S/C29H26FN5O3S/c30-21-5-8-25(36)24(16-21)26(27(37)33-29-32-11-14-39-29)35-17-20-2-1-19(15-23(20)28(35)38)18-3-6-22(7-4-18)34-12-9-31-10-13-34/h1-8,11,14-16,26,31,36H,9-10,12-13,17H2,(H,32,33,37)/t26-/m1/s1
Bioactivity Comments
JBJ-04-125-02 inhibits EGFRL858R/T790M/C797S signalling, and cell proliferation in vitro and in vivo [1]. It is unable to bind Del_19-containing EGFR mutants, and does not inhibit proliferation of parental Ba/F3, wild-type EGFR Ba/F3 cells or Ba/F3 cells expressing any of the EGFRDel_19 variants.
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 9.6 pIC50 - 1
pIC50 9.6 (IC50 2.6x10-10 M) [1]
Description: Inhibition of EGFRL858R/T790M in a biochemical assay