example 10 [CN110740999A]   Click here for help

GtoPdb Ligand ID: 12952

Synonyms: compound 40 [PMID: 34323489] [4]
Compound class: Synthetic organic
Comment: This chemical structure was extracted from a patent claiming fourth generation EGFR inhibitors [2]. Based on a chemical structure that was submitted to the Cambridge Crystallographic Data Centre (Deposition number 2261855), and in the absence of a disclosed name-to-structure, we predict that this is likely to be the clinical lead EGFR inhibitor BBT-176 (or is closely related to it) as written about in [3].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 11
Hydrogen bond donors 3
Rotatable bonds 9
Topological polar surface area 122.28
Molecular weight 601.17
XLogP 1.65
No. Lipinski's rules broken 2
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Canonical SMILES CN1CCN(CC1)C2CCN(CC2)C3=CC=C(C(=C3)OC)NC4=NC(=C(C=N4)Cl)NC5=C(C=CC=C5)NS(=O)(=O)C
InChI InChI=1S/C28H37ClN8O3S/c1-35-14-16-37(17-15-35)20-10-12-36(13-11-20)21-8-9-25(26(18-21)40-2)32-28-30-19-22(29)27(33-28)31-23-6-4-5-7-24(23)34-41(3,38)39/h4-9,18-20,34H,10-17H2,1-3H3,(H2,30,31,32,33)
Bioactivity Comments
This inhibitor retains activity against EGFR with the C797S kinase domain mutation that confers osimertinib resistance [1-2].
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 6.4 – 9.7 pIC50 - 2
pIC50 9.7 (IC50 2x10-10 M) [2]
Description: Inhibition of EGFR with triple del19/T790M/C797S mutation in an enzymatic assay
pIC50 9.1 (IC50 7x10-10 M) [2]
Description: Inhibition of EGFR with del19 mutation in an enzymatic assay
pIC50 8.4 (IC50 4x10-9 M) [2]
Description: Inhibition of EGFR with dual del19/T790M mutation in an enzymatic assay
pIC50 6.4 (IC50 4.3x10-7 M) [2]
Description: Inhibition of WT EGFR in an enzymatic assay