brigatinib   Click here for help

GtoPdb Ligand ID: 7741

Synonyms: Alunbrig® | AP-26113 | AP26113 | compound 11q [PMID: 27144831]
Approved drug PDB Ligand
brigatinib is an approved drug (FDA (2017), EMA (2018))
Compound class: Synthetic organic
Comment: Brigatinib (AP26113) is a phosphine oxide-containing drug developed as a treatment for cancers driven by anaplastic lymphoma kinase (ALK) rearrangements [1] or by T790M gatekeeper mutant EGFR. It is an orally available inhibitor.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 8
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 95.67
Molecular weight 583.26
XLogP 5.11
No. Lipinski's rules broken 1
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Canonical SMILES COc1cc(ccc1Nc1ncc(c(n1)Nc1ccccc1P(=O)(C)C)Cl)N1CCC(CC1)N1CCN(CC1)C
Isomeric SMILES COc1cc(ccc1Nc1ncc(c(n1)Nc1ccccc1P(=O)(C)C)Cl)N1CCC(CC1)N1CCN(CC1)C
InChI InChI=1S/C29H39ClN7O2P/c1-35-15-17-37(18-16-35)21-11-13-36(14-12-21)22-9-10-24(26(19-22)39-2)33-29-31-20-23(30)28(34-29)32-25-7-5-6-8-27(25)40(3,4)38/h5-10,19-21H,11-18H2,1-4H3,(H2,31,32,33,34)
Bioactivity Comments
Brigatinib exhibits low nM IC50s against wild-type ALK and clinically relevant ALK mutants in enzyme-based biochemical and cell viability assays [1]. Brigatinib is highly active against crizotinib resistant cancer cells in vitro and in vivo [2].
Selectivity at catalytic receptors
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
ALK receptor tyrosine kinase Primary target of this compound Hs Inhibitor Inhibition 10.1 pKi - 2
pKi 10.1 (Ki 9x10-11 M) [2]
Description: Wild type ALK
ALK receptor tyrosine kinase Primary target of this compound Hs Inhibitor Inhibition 9.2 – 9.4 pIC50 - 1-2
pIC50 9.2 – 9.4 (IC50 6.2x10-10 – 3.7x10-10 M) [1-2]
Insulin-like growth factor I receptor Hs Inhibitor Inhibition 7.6 pIC50 - 1
pIC50 7.6 (IC50 2.46x10-8 M) [1]
epidermal growth factor receptor Hs Inhibitor Inhibition 6.9 pIC50 - 2
pIC50 6.9 (IC50 1.29x10-7 M) [2]
Insulin receptor Hs Inhibitor Inhibition 6.7 pIC50 - 1
pIC50 6.7 (IC50 1.96x10-7 M) [1]