brigatinib Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 5233 1197953-54-0

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • brigatinib
  • alunbrig
  • AP26113
Brigatinib is a tyrosine kinase inhibitor with in vitro activity at clinically achievable concentrations against multiple kinases including ALK, ROS1, insulin-like growth factor-1 receptor (IGF-1R), and FLT-3 as well as EGFR deletion and point mutations. Brigatinib inhibited autophosphorylation of ALK and ALK-mediated phosphorylation of the downstream signaling proteins STAT3, AKT, ERK1/2, and S6 in in vitro and in vivo assays. Brigatinib also inhibited the in vitro proliferation of cell lines expressing EML4-ALK and NPM-ALK fusion proteins and demonstrated dose-dependent inhibition of EML4-ALK-positive NSCLC xenograft growth in mice. At clinically achievable concentrations (<= 500 nM), brigatinib inhibited the in vitro viability of cells expressing EML4-ALK and 17 mutant forms associated with resistance to ALK inhibitors including crizotinib, as well as EGFR-Del (E746-A750), ROS1-L2026M, FLT3-F691L, and FLT3-D835Y. Brigatinib exhibited in vivo anti-tumor activity against 4 mutant forms of EML4-ALK, including G1202R and L1196M mutants identified in NSCLC tumors in patients who have progressed on crizotinib. Brigatinib also reduced tumor burden and prolonged survival in mice implanted intracranially with an ALK-driven tumor cell line.
  • Molecular weight: 584.10
  • Formula: C29H39ClN7O2P
  • CLOGP: 1.72
  • LIPINSKI: 1
  • HAC: 9
  • HDO: 2
  • TPSA: 85.86
  • ALOGS: -4.42
  • ROTB: 8

  • Status: ONP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

None

Approvals:

DateAgencyCompanyOrphan
Sept. 22, 2018 EMA TAKEDA PHARMA A/S
April 28, 2017 FDA ARIAD

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Neoplasm progression 228.33 45.36 56 587 26627 46658792
Non-small cell lung cancer 96.92 45.36 19 624 3125 46682294
Metastases to central nervous system 63.29 45.36 17 626 11204 46674215
Blood creatine phosphokinase increased 48.13 45.36 17 626 27707 46657712

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Neoplasm progression 131.92 50.22 32 303 17991 29934152
Non-small cell lung cancer 67.76 50.22 14 321 3716 29948427

Pharmacologic Action:

SourceCodeDescription
ATC L01ED04 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Anaplastic lymphoma kinase (ALK) inhibitors
FDA MoA N0000020001 Tyrosine Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000190118 Cytochrome P450 3A Inducers

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Non-small cell lung cancer indication 254637007 DOID:3908

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.76 Basic
pKa2 5.51 Basic
pKa3 4.76 Basic
pKa4 2.49 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
180MG ALUNBRIG TAKEDA PHARMS USA N208772 Oct. 2, 2017 RX TABLET ORAL April 28, 2022 NEW CHEMICAL ENTITY
30MG ALUNBRIG TAKEDA PHARMS USA N208772 April 28, 2017 RX TABLET ORAL April 28, 2022 NEW CHEMICAL ENTITY
90MG ALUNBRIG TAKEDA PHARMS USA N208772 April 28, 2017 RX TABLET ORAL April 28, 2022 NEW CHEMICAL ENTITY
180MG ALUNBRIG TAKEDA PHARMS USA N208772 Oct. 2, 2017 RX TABLET ORAL May 22, 2023 EXPANDED INDICATION OF THE TREATMENT OF ADULT PATIENTS WITH ANULLPLASTIC LYMPHOMA KINULLSE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) AS DETECTED BY AN FDA-APPROVED TEST
30MG ALUNBRIG TAKEDA PHARMS USA N208772 April 28, 2017 RX TABLET ORAL May 22, 2023 EXPANDED INDICATION OF THE TREATMENT OF ADULT PATIENTS WITH ANULLPLASTIC LYMPHOMA KINULLSE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) AS DETECTED BY AN FDA-APPROVED TEST
90MG ALUNBRIG TAKEDA PHARMS USA N208772 April 28, 2017 RX TABLET ORAL May 22, 2023 EXPANDED INDICATION OF THE TREATMENT OF ADULT PATIENTS WITH ANULLPLASTIC LYMPHOMA KINULLSE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) AS DETECTED BY AN FDA-APPROVED TEST
180MG ALUNBRIG TAKEDA PHARMS USA N208772 Oct. 2, 2017 RX TABLET ORAL April 28, 2024 TREATMENT OF PATIENTS WITH ANULLPLASTIC LYMPHOMA KINULLSE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHO HAVE PROGRESSED ON OR ARE INTOLERANT TO CRIZOTINIB
30MG ALUNBRIG TAKEDA PHARMS USA N208772 April 28, 2017 RX TABLET ORAL April 28, 2024 TREATMENT OF PATIENTS WITH ANULLPLASTIC LYMPHOMA KINULLSE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHO HAVE PROGRESSED ON OR ARE INTOLERANT TO CRIZOTINIB
90MG ALUNBRIG TAKEDA PHARMS USA N208772 April 28, 2017 RX TABLET ORAL April 28, 2024 TREATMENT OF PATIENTS WITH ANULLPLASTIC LYMPHOMA KINULLSE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHO HAVE PROGRESSED ON OR ARE INTOLERANT TO CRIZOTINIB
180MG ALUNBRIG TAKEDA PHARMS USA N208772 Oct. 2, 2017 RX TABLET ORAL May 22, 2027 FOR THE TREATMENT OF ADULT PATIENTS WITH ANULLPLASTIC LYMPHOMA KINULLSE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) AS DETECTED BY AN FDA-APPROVED TEST, NOT INCLUDING PATIENTS WHO HAVE PROGRESSED ON OR ARE INTOLERANT TO CRIZOTINIB
30MG ALUNBRIG TAKEDA PHARMS USA N208772 April 28, 2017 RX TABLET ORAL May 22, 2027 FOR THE TREATMENT OF ADULT PATIENTS WITH ANULLPLASTIC LYMPHOMA KINULLSE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) AS DETECTED BY AN FDA-APPROVED TEST, NOT INCLUDING PATIENTS WHO HAVE PROGRESSED ON OR ARE INTOLERANT TO CRIZOTINIB
90MG ALUNBRIG TAKEDA PHARMS USA N208772 April 28, 2017 RX TABLET ORAL May 22, 2027 FOR THE TREATMENT OF ADULT PATIENTS WITH ANULLPLASTIC LYMPHOMA KINULLSE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) AS DETECTED BY AN FDA-APPROVED TEST, NOT INCLUDING PATIENTS WHO HAVE PROGRESSED ON OR ARE INTOLERANT TO CRIZOTINIB

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
ALK tyrosine kinase receptor Kinase INHIBITOR IC50 9.22 SCIENTIFIC LITERATURE DRUG LABEL
Proto-oncogene tyrosine-protein kinase ROS Kinase INHIBITOR IC50 8.72 SCIENTIFIC LITERATURE
Receptor-type tyrosine-protein kinase FLT3 Kinase INHIBITOR IC50 8.68 SCIENTIFIC LITERATURE
Epidermal growth factor receptor Kinase INHIBITOR IC50 7.17 SCIENTIFIC LITERATURE
Insulin-like growth factor 1 receptor Kinase INHIBITOR IC50 7.14 SCIENTIFIC LITERATURE
Insulin receptor Kinase INHIBITOR IC50 6.80 SCIENTIFIC LITERATURE

External reference:

IDSource
HYW8DB273J UNII
4036651 VANDF
C4475146 UMLSCUI
6GY PDB_CHEM_ID
CHEMBL3545311 ChEMBL_ID
DB12267 DRUGBANK_ID
D10866 KEGG_DRUG
68165256 PUBCHEM_CID
10085 INN_ID
C000598580 MESH_SUPPLEMENTAL_RECORD_UI
7741 IUPHAR_LIGAND_ID
1921217 RXNORM
256904 MMSL
32700 MMSL
d08581 MMSL
017195 NDDF
736634002 SNOMEDCT_US
763704002 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Alunbrig HUMAN PRESCRIPTION DRUG LABEL 1 63020-090 TABLET, FILM COATED 90 mg ORAL NDA 31 sections
Alunbrig HUMAN PRESCRIPTION DRUG LABEL 1 63020-113 TABLET, FILM COATED 30 mg ORAL NDA 31 sections
Alunbrig HUMAN PRESCRIPTION DRUG LABEL 1 63020-180 TABLET, FILM COATED 180 mg ORAL NDA 31 sections