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]
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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)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

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
DrugBank ID: DB12267
TTD ID: D08PIE
VARIDT ID: DR00368
INTEDE ID: DR0228
ACDINA ID: D00077

Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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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]

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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]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2C8 (CYP2C8)_{Main DME}	DES5XRU	CP2C8_HUMAN	Substrate	[6]

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Molecular Interaction Atlas (MIA)

MIA Detail

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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)

MEA Detail

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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]
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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]
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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
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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

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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.