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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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

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View more information in the IUPHAR Pharmacology Education Project: brigatinib

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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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
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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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)
InChI Key AILRADAXUVEEIR-UHFFFAOYSA-N
No information available.
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 ClinicalTrials.gov.
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