Details of the Drug

General Information of Drug (ID: DM7W94S)

Drug Name
Brigatinib
Synonyms
1197953-54-0; UNII-HYW8DB273J; Brigatinib [USAN]; ALUNBRIG; HYW8DB273J; Brigatinib (USAN); Brigatiib; Alunbrig (TN); Brigatinib [USAN:INN]; Brigatinib (AP26113); SCHEMBL11916361; KS-00000TSQ; EX-A775; MolPort-044-561-640; BDBM50185140; ZINC148723177; AKOS030257612; CS-4278; DB12267; HY-12857; AC-29958
Indication
Disease Entry ICD 11 Status REF
Anaplastic large cell lymphoma 2A90.A Approved [1]
Non-small-cell lung cancer 2C25.Y Approved [2]
Affected Organisms
Humans and other mammals
ATC Code
L01ED04: Brigatinib
L01ED: Anaplastic lymphoma kinase (ALK) inhibitors
L01E: PROTEIN KINASE INHIBITORS
L01: ANTINEOPLASTIC AGENTS
L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 584.1
Logarithm of the Partition Coefficient (xlogp) 4.6
Rotatable Bond Count (rotbonds) 8
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 9
ADMET Property
Absorption AUC
The area under the plot of plasma concentration (AUC) of drug is 8165 mcgh/L [3]
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 552 mcg/L [3]
Clearance
The apparent oral clearance of drug is 12.7 L/h [4]
Elimination
The elimination of brigatinib is divided in 65% in feces and 25% in urine [4]
Half-life
The concentration or amount of drug in body reduced by one-half in 25 hours [4]
Metabolism
The drug is metabolized via the CYP2C8 [4]
Vd
The volume of distribution (Vd) of drug is 153 L [3]
Chemical Identifiers
Formula
C29H39ClN7O2P
IUPAC Name
5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]pyrimidine-2,4-diamine
Canonical SMILES
CN1CCN(CC1)C2CCN(CC2)C3=CC(=C(C=C3)NC4=NC=C(C(=N4)NC5=CC=CC=C5P(=O)(C)C)Cl)OC
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)
InChIKey
AILRADAXUVEEIR-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
68165256
CAS Number
1197953-54-0
UNII
HYW8DB273J
DrugBank ID
DB12267
TTD ID
D08PIE
VARIDT ID
DR00368
INTEDE ID
DR0228
ACDINA ID
D00077
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
ALK tyrosine kinase receptor (ALK) TTPMQSO ALK_HUMAN Inhibitor [1]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
ATP-binding cassette sub-family B member 5 (ABCB5) DTKVEXO ABCB5_HUMAN Substrate [5]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [5]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 2C8 (CYP2C8)
Main DME 		DES5XRU CP2C8_HUMAN Substrate [6]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Anaplastic large cell lymphoma
ICD Disease Classification 2A90.A
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
ALK tyrosine kinase receptor (ALK) DTT ALK 7.19E-15 0.18 0.61
ATP-binding cassette sub-family B member 5 (ABCB5) DTP ABCB5 5.60E-01 -1.37E-02 -1.15E-01
Breast cancer resistance protein (ABCG2) DTP BCRP 3.87E-47 -1.28E+00 -1.63E+00
Cytochrome P450 2C8 (CYP2C8) DME CYP2C8 5.28E-05 1.90E-02 1.09E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Brigatinib
DDI Drug Name DDI Drug ID Severity Mechanism Disease REF
Selpercatinib DMZR15V Moderate Increased metabolism of Brigatinib caused by Selpercatinib mediated induction of CYP450 enzyme. Lung cancer [2C25] [7]
Coadministration of a Drug Treating the Disease Different from Brigatinib (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Ivosidenib DM8S6T7 Moderate Increased metabolism of Brigatinib caused by Ivosidenib mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [8]
Oliceridine DM6MDCF Moderate Increased metabolism of Brigatinib caused by Oliceridine mediated induction of CYP450 enzyme. Acute pain [MG31] [9]
Troleandomycin DMUZNIG Major Decreased metabolism of Brigatinib caused by Troleandomycin mediated inhibition of CYP450 enzyme. Bacterial infection [1A00-1C4Z] [10]
Pexidartinib DMS2J0Z Major Increased metabolism of Brigatinib caused by Pexidartinib mediated induction of CYP450 enzyme. Bone/articular cartilage neoplasm [2F7B] [8]
Eslicarbazepine DMZREFQ Major Increased metabolism of Brigatinib caused by Eslicarbazepine mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [8]
Bay 80-6946 DMLOS5R Moderate Increased metabolism of Brigatinib caused by Bay 80-6946 mediated induction of CYP450 enzyme. Follicular lymphoma [2A80] [11]
Tazemetostat DMWP1BH Moderate Increased metabolism of Brigatinib caused by Tazemetostat mediated induction of CYP450 enzyme. Follicular lymphoma [2A80] [8]
Ripretinib DM958QB Moderate Increased metabolism of Brigatinib caused by Ripretinib mediated induction of CYP450 enzyme. Gastrointestinal stromal tumour [2B5B] [8]
Avapritinib DMK2GZX Moderate Increased metabolism of Brigatinib caused by Avapritinib mediated induction of CYP450 enzyme. Gastrointestinal stromal tumour [2B5B] [7]
MK-1439 DM215WE Moderate Increased metabolism of Brigatinib caused by MK-1439 mediated induction of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [12]
Berotralstat DMWA2DZ Moderate Decreased metabolism of Brigatinib caused by Berotralstat mediated inhibition of CYP450 enzyme. Innate/adaptive immunodeficiency [4A00] [8]
Pemigatinib DM819JF Moderate Increased metabolism of Brigatinib caused by Pemigatinib mediated induction of CYP450 enzyme. Liver cancer [2C12] [7]
Ubrogepant DM749I3 Moderate Increased metabolism of Brigatinib caused by Ubrogepant mediated induction of CYP450 enzyme. Migraine [8A80] [13]
Siponimod DM2R86O Major Additive immunosuppressive effects by the combination of Brigatinib and Siponimod. Multiple sclerosis [8A40] [8]
Ozanimod DMT6AM2 Major Additive immunosuppressive effects by the combination of Brigatinib and Ozanimod. Multiple sclerosis [8A40] [7]
Fedratinib DM4ZBK6 Major Decreased metabolism of Brigatinib caused by Fedratinib mediated inhibition of CYP450 enzyme. Myeloproliferative neoplasm [2A20] [8]
Rucaparib DM9PVX8 Moderate Decreased metabolism of Brigatinib caused by Rucaparib mediated inhibition of CYP450 enzyme. Ovarian cancer [2C73] [8]
Macimorelin DMQYJIR Moderate Increased metabolism of Brigatinib caused by Macimorelin mediated induction of CYP450 enzyme. Pituitary gland disorder [5A60-5A61] [14]
Lefamulin DME6G97 Moderate Increased metabolism of Brigatinib caused by Lefamulin mediated induction of CYP450 enzyme. Pneumonia [CA40] [15]
Darolutamide DMV7YFT Moderate Increased metabolism of Brigatinib caused by Darolutamide mediated induction of CYP450 enzyme. Prostate cancer [2C82] [16]
Voxelotor DMCS6M5 Major Decreased metabolism of Brigatinib caused by Voxelotor mediated inhibition of CYP450 enzyme. Sickle-cell disorder [3A51] [8]
Larotrectinib DM26CQR Moderate Increased metabolism of Brigatinib caused by Larotrectinib mediated induction of CYP450 enzyme. Solid tumour/cancer [2A00-2F9Z] [8]
Betrixaban DM2C4RF Moderate Decreased clearance of Brigatinib due to the transporter inhibition by Betrixaban. Venous thromboembolism [BD72] [17]
⏷ Show the Full List of 23 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Lactose monohydrate E00393 104938 Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate E00208 11177 lubricant
Silicon dioxide E00670 Not Available Anticaking agent; Opacifying agent; Viscosity-controlling agent
Water E00035 962 Solvent
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Brigatinib 180 mg tablet 180 mg Oral Tablet Oral
Brigatinib 90 mg tablet 90 mg Oral Tablet Oral
Brigatinib 30 mg tablet 30 mg Oral Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2018
3 Markham A: Brigatinib: First Global Approval. Drugs. 2017 Jul;77(10):1131-1135. doi: 10.1007/s40265-017-0776-3.
4 FDA Reports
5 NDA/BLA Multidisciplinary Review and Evaluation of ALUNBRIG (brigatinib) From FDA.
6 Brigatinib: first global approval. Drugs. 2017 Jul;77(10):1131-1135.
7 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
8 Cerner Multum, Inc. "Australian Product Information.".
9 Altice FL, Friedland GH, Cooney EL "Nevirapine induced opiate withdrawal among injection drug users with HIV infection receiving methadone." AIDS 13 (1999): 957-62. [PMID: 10371177]
10 Product Information. Alunbrig (brigatinib). Ariad Pharmaceuticals Inc, Cambridge, MA.
11 Product Information. Aliqopa (copanlisib). Bayer Pharmaceutical Inc, West Haven, CT.
12 Product Information. Pifeltro (doravirine). Merck & Company Inc, Whitehouse Station, NJ.
13 Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
14 Product Information. Macrilen (macimorelin). Aeterna Zentaris, Charleston, SC.
15 Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
16 Product Information. Nubeqa (darolutamide). Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ.
17 Product Information. Bevyxxa (betrixaban). Portola Pharmaceuticals, South San Francisco, CA.