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)
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Summary of Clinical Use Click here for help
Brigatinib (AP26113) received Breakthrough Therapy designation from the U.S. FDA for the treatment of patients with ALK-rearranged metastatic NSCLC whose tumours are resistant to crizotinib. This was converted via accelerated approval for these patients in April 2017. Phase 3 trial NCT02737501 compared brigatinib and crizotinib 'head-to-head'. Click here to view the list of all AP26113 trials currently registered with
Mechanism Of Action and Pharmacodynamic Effects Click here for help
ALK was first identified as a chromosomal rearrangement in anaplastic large-cell lymphoma (ALCL), and has since been shown to be a driver of some non-small cell lung cancers (NSCLCs) and neuroblastomas, in addition to ALCL. ALK is not normally expressed in normal adult tissues, making it a promising molecular target for oncology.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02737501 ALTA-1L Study: A Phase 3 Study of Brigatinib Versus Crizotinib in Anaplastic Lymphoma Kinase (ALK)-Positive Advanced Non-small Cell Lung Cancer (NSCLC) Participants Phase 3 Interventional Takeda