Brigatinib

Identification

Summary

Brigatinib is an anaplastic lymphoma kinase inhibitor used to treat anaplastic lymphoma kinase positive metastatic non small cell lung cancer.

Brand Names

Alunbrig

Generic Name

Brigatinib

DrugBank Accession Number

DB12267

Background

Brigatinib, originally named AP26113, is a reversible dual inhibitor of anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR). It presents selectivity against the mutant forms of EGFR compared to the wild-type.¹ It also exhibits selectivity against 9 different Crizotinib-resistant mutants of the EML4-ALK fusion gene, which is a pivotal player in the transformation of susceptible lung parenchyma.² Brigatinib was developed by Ariad Pharmaceuticals, a subsidiary of Takeda Pharmaceutical Company Limited, and FDA-approved on April 28, 2017.⁹

Type

Small Molecule

Groups

Approved, Investigational

Structure

Similar Structures

Weight: Average: 584.1
Monoisotopic: 583.2591382
Chemical Formula: C₂₉H₃₉ClN₇O₂P

Synonyms

Brigatinib

External IDs

AP-26113
AP26113

Poor quality drug data slowing you down?

Unlock 38% more drug discovery time and eliminate decision-making doubts with this one-stop guide to quality drug data.

Download eBook

Poor quality drug data slowing you down?

Download eBook

Pharmacology

Indication

The anaplastic lymphoma kinase positive, metastatic non-small cell lung cancer (ALK+ NSCLC), represents only 3-5% of the NSCLC cancer cases, but the ALK mutation, overexpression and presence in several oncogenic fusion proteins in solid and hematologic tumors have pointed out the importance as well as its potential as a cancer therapy target.¹ The ALK-related cases of NSCLC are associated with the presence of the fusion gene EML4-ALK which fused the ALK protein with the echinoderm microtubule-associated protein like-4 whose original function is the correct formation of microtubules.² The presence of the aberrant fusion protein results in abnormal signaling that provokes increased cell growth, proliferation and survival.⁴ Crizotinib is indicated for the treatment of such cases but the presence of ALK kinase domain mutations confer resistance to the treatment. Thus, brigatinib is indicated for the treatment of patients with ALK+ NSCLC with intolerance to Crizotinib.³

Reduce drug development failure rates

Build, train, & validate machine-learning models
with evidence-based and structured datasets.

See how

Build, train, & validate predictive machine-learning models with structured datasets.

See how

Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Treatment of	Metastatic non-small cell lung cancer		••••••••••••	•••••	•••• •••••••••• •• •• ••• •••••••••• •• ••••••••••

Contraindications & Blackbox Warnings

Prevent Adverse Drug Events Today

Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.

Learn more

Avoid life-threatening adverse drug events with our Clinical API

Learn more

Pharmacodynamics

Brigitanib inhibits proliferation and in vitro viability of cells expressing the fusion protein EML4-ALK as well as 17 crizotinib-resistant ALK mutants. Its action is expanded to cells expressing EGFR deletions, ROS1-L2026M, FLT3-F691L and FLT3-D835Y.⁵ Brigitanib presents a dose-dependent inhibition of tumor growth, tumor burden and prolonged survival in mice EML4-ALK xenograft models.⁶ Time course of Brigatinib and exposure-response studies are still unknown.

Mechanism of action

Brigitanib acts as a tyrosine kinase inhibitor with activity against multiple kinases including ALK, ROS1, insulin-like growth factor 1 receptor and against EGFR deletions and point mutations. It acts by inhibiting ALK phosphorylation and the activation of downstream signaling proteins.⁷

Target	Actions	Organism
AALK tyrosine kinase receptor	inhibitor	Humans
AEpidermal growth factor receptor	inhibitor	Humans
UTyrosine-protein kinase ABL1	inhibitor	Humans
UInsulin-like growth factor 1 receptor	inhibitor	Humans
UReceptor-type tyrosine-protein kinase FLT3	inhibitor	Humans
NInsulin receptor	binding	Humans
UHepatocyte growth factor receptor	inhibitor	Humans
UReceptor tyrosine-protein kinase erbB-4	inhibitor	Humans
UReceptor tyrosine-protein kinase erbB-2	inhibitor	Humans

Absorption

Administration of brigatinib at a concentration of 90 mg generates a Cmax of 552 ng/ml and AUC of 8165 ng h/ml while the administration of 180 mg presents a Cmax of 1452 ng/ml and AUC of 20276 ng h/ml. It has a dose proportional exposure with an accumulation ratio on the range of 1.9 to 2.4. Following oral administration of brigatinib, the Tmax is presented in a range from 1 to 4 hours. Consumption of a high-fat meal compared to overnight fasting reduces Cmax by 13% without presenting an effect on AUC.⁸

Volume of distribution

The apparent volume of distribution at steady state is 153 L.⁸

Protein binding

66% of brigatinib dose is bound to plasma proteins, which gives a blood-to-plasma concentration ratio of 0.69.⁸

Metabolism

Brigatinib is metabolized by CYP2C8 (72.4%) and CYP3A4 (27.6%) in human liver microsomes and hepatocytes. The two major metabolites generated are the N-demethylated form and the cysteine conjugated form. Oral administration of radiolabelled brigatinib showed the systemic presence of 91.5% in the unchanged form and 3.5% of the primary metabolite AP26123. The AUC of AP26123 is less than 10% of the AUC of brigatinib and presented an inhibitory effect 3 fold lower.¹⁰

Hover over products below to view reaction partners

Brigatinib
- AP26123

Route of elimination

The elimination of brigatinib is divided in 65% in feces and 25% in urine. From the elimination in both compartments, the unchanged for of brigatinib represented 41% of the total in feces and 86% in urine.¹⁰

Half-life

The half-life of brigatinib at steady-state was 25 hours.¹⁰

Clearance

After oral administration of180 mg of brigatinib, the apparent oral clearance at steady-state is 12.7 L/h.¹⁰

Adverse Effects

Improve decision support & research outcomes

With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!

See the data

Improve decision support & research outcomes with our structured adverse effects data.

See a data sample

Toxicity

Treatment with brigatinib generated not mutagenic chromosomal damage. Testicular toxicity, reported as lower weight of seminal vesicles and prostate gland, testicular tubular degeneration and lower weight as well as reduced size of testes with evidence of hypoespermatogenesis.^Label

Pathways

Not Available

Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">

Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
Integrate drug-drug interactions in your software
Abametapir	The serum concentration of Brigatinib can be increased when it is combined with Abametapir.
Abatacept	The metabolism of Brigatinib can be increased when combined with Abatacept.
Abemaciclib	The excretion of Abemaciclib can be decreased when combined with Brigatinib.
Abiraterone	The metabolism of Brigatinib can be decreased when combined with Abiraterone.
Acalabrutinib	The metabolism of Brigatinib can be decreased when combined with Acalabrutinib.

Food Interactions

Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of brigatinib.
Avoid St. John's Wort. This herb induces the CYP3A metabolism of brigatinib and may reduce its serum concentration.
Take with or without food.

Products

Drug product information from 10+ global regions

Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.

Access now

Access drug product information from over 10 global regions.

Access now

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Alunbrig	Tablet, film coated	30 mg	Oral	Takeda Pharma A/S	2020-12-16	Not applicable
Alunbrig	Tablet	180 mg	Oral	Takeda	2018-08-31	Not applicable
Alunbrig	Tablet, film coated	90 mg	Oral	Takeda Pharma A/S	2020-12-16	Not applicable
Alunbrig	Tablet, film coated	180 mg/1	Oral	Takeda Pharmaceuticals America, Inc.	2017-04-28	Not applicable
Alunbrig	Tablet, film coated	90 mg	Oral	Takeda Pharma A/S	2020-12-16	Not applicable

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
ALUNBRIG	Brigatinib (90 MG) + Brigatinib (180 MG)	Tablet, film coated	Oral	Takeda Pharma A/S	2020-03-03	Not applicable
Alunbrig	Brigatinib (90 mg) + Brigatinib (180 mg)	Kit; Tablet	Oral	Takeda	2018-08-31	Not applicable
Alunbrig	Brigatinib (90 mg/1) + Brigatinib (180 mg/1)	Kit; Tablet, film coated	Oral	Takeda Pharmaceuticals America, Inc.	2017-04-28	Not applicable
Alunbrig	Brigatinib (90 mg) + Brigatinib (180 mg)	Kit; Tablet	Oral	Takeda	2018-08-31	Not applicable
ALUNBRIG	Brigatinib (90 MG) + Brigatinib (180 MG)	Tablet, film coated	Oral	Takeda Pharma A/S	2020-03-03	Not applicable

Chemical Identifiers

UNII: HYW8DB273J
CAS number: 1197953-54-0
InChI Key: AILRADAXUVEEIR-UHFFFAOYSA-N
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)
IUPAC Name: 5-chloro-N4-[2-(dimethylphosphoryl)phenyl]-N2-{2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}pyrimidine-2,4-diamine
SMILES: COC1=CC(=CC=C1NC1=NC=C(Cl)C(NC2=CC=CC=C2P(C)(C)=O)=N1)N1CCC(CC1)N1CCN(C)CC1

References

General References

Ceccon M, Mologni L, Bisson W, Scapozza L, Gambacorti-Passerini C: Crizotinib-resistant NPM-ALK mutants confer differential sensitivity to unrelated Alk inhibitors. Mol Cancer Res. 2013 Feb;11(2):122-32. doi: 10.1158/1541-7786.MCR-12-0569. Epub 2012 Dec 13. [Article]
Iragavarapu C, Mustafa M, Akinleye A, Furqan M, Mittal V, Cang S, Liu D: Novel ALK inhibitors in clinical use and development. J Hematol Oncol. 2015 Feb 27;8:17. doi: 10.1186/s13045-015-0122-8. [Article]
Rashdan S, Gerber DE: A crowded, but still varied, space: brigatinib in anaplastic lymphoma kinase-rearranged non-small cell lung cancer. Transl Cancer Res. 2017 Feb;6(Suppl 1):S78-S82. doi: 10.21037/tcr.2017.02.12. [Article]
Sabir SR, Yeoh S, Jackson G, Bayliss R: EML4-ALK Variants: Biological and Molecular Properties, and the Implications for Patients. Cancers (Basel). 2017 Sep 5;9(9). pii: E118. doi: 10.3390/cancers9090118. [Article]
Sabari JK, Santini FC, Schram AM, Bergagnini I, Chen R, Mrad C, Lai WV, Arbour KC, Drilon A: The activity, safety, and evolving role of brigatinib in patients with ALK-rearranged non-small cell lung cancers. Onco Targets Ther. 2017 Apr 6;10:1983-1992. doi: 10.2147/OTT.S109295. eCollection 2017. [Article]
Siaw JT, Wan H, Pfeifer K, Rivera VM, Guan J, Palmer RH, Hallberg B: Brigatinib, an anaplastic lymphoma kinase inhibitor, abrogates activity and growth in ALK-positive neuroblastoma cells, Drosophila and mice. Oncotarget. 2016 May 17;7(20):29011-22. doi: 10.18632/oncotarget.8508. [Article]
Huang WS, Liu S, Zou D, Thomas M, Wang Y, Zhou T, Romero J, Kohlmann A, Li F, Qi J, Cai L, Dwight TA, Xu Y, Xu R, Dodd R, Toms A, Parillon L, Lu X, Anjum R, Zhang S, Wang F, Keats J, Wardwell SD, Ning Y, Xu Q, Moran LE, Mohemmad QK, Jang HG, Clackson T, Narasimhan NI, Rivera VM, Zhu X, Dalgarno D, Shakespeare WC: Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing, Potent, Orally Active Inhibitor of Anaplastic Lymphoma Kinase. J Med Chem. 2016 May 26;59(10):4948-64. doi: 10.1021/acs.jmedchem.6b00306. Epub 2016 May 12. [Article]
Markham A: Brigatinib: First Global Approval. Drugs. 2017 Jul;77(10):1131-1135. doi: 10.1007/s40265-017-0776-3. [Article]
FDA News and Events [Link]
FDA Reports [Link]

External Links

PubChem Compound: 68165256
PubChem Substance: 347828538
ChemSpider: 34982928
BindingDB: 50185140
RxNav: 1921217
ChEMBL: CHEMBL3545311
ZINC: ZINC000148723177
PharmGKB: PA166163482
PDBe Ligand: 6GY
Wikipedia: Brigatinib

PDB Entries

6mx8 / 7aem / 7zym / 8h7x

FDA label

Download (595 KB)

MSDS

Download (25.2 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
3	Active Not Recruiting	Treatment	ALK+ Advanced NSCLC	1
3	Completed	Treatment	Advanced Malignant Neoplasm / Carcinoma / Lung Cancer / Non-Small Cell Lung Cancer (NSCLC)	1
2	Active Not Recruiting	Treatment	ALK-positive Advanced NSCLC	1
2	Active Not Recruiting	Treatment	Breast Cancer / Gastrointestinal Tract Cancer / Non-Small Cell Lung Cancer (NSCLC) / Other Cancers	1
2	Active Not Recruiting	Treatment	Lung Cancer / Non-Small Cell Lung Cancer (NSCLC) / Stage IIIB Non-Small Cell Lung Cancer / Stage IV Non-small Cell Lung Cancer (NSCLC)	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Kit; tablet	Oral
Kit; tablet, film coated	Oral
Tablet	Oral	180 mg
Tablet	Oral	30 mg
Tablet	Oral	90 mg
Tablet, coated	Oral	30 mg/1
Tablet, film coated	Oral
Tablet, film coated	Oral	180 mg/1
Tablet, film coated	Oral	30 mg/1
Tablet, film coated	Oral	90 mg/1
Tablet, coated	Oral	180 mg
Tablet, coated	Oral	30 mg
Tablet, coated	Oral	90 mg
Tablet, film coated	Oral	180 mg
Tablet, film coated	Oral	30 mg
Tablet, film coated	Oral	90 mg
Tablet, film coated	Oral

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US9012462	No	2015-04-21	2031-02-06
US9611283	No	2017-04-04	2034-04-10
US9273077	No	2016-03-01	2029-05-21
US10385078	No	2019-08-20	2035-11-10

Properties

State

Solid

Experimental Properties

Property	Value	Source
water solubility	Insoluble	Selleckchem, MSDS
logP	5.17	Molbase, MSDS

Predicted Properties

Property	Value	Source
Water Solubility	0.022 mg/mL	ALOGPS
logP	5.11	ALOGPS
logP	3.66	Chemaxon
logS	-4.4	ALOGPS
pKa (Strongest Acidic)	12.88	Chemaxon
pKa (Strongest Basic)	8.54	Chemaxon
Physiological Charge	1	Chemaxon
Hydrogen Acceptor Count	9	Chemaxon
Hydrogen Donor Count	2	Chemaxon
Polar Surface Area	85.86 Å²	Chemaxon
Rotatable Bond Count	8	Chemaxon
Refractivity	164.77 m³·mol^-1	Chemaxon
Polarizability	64.1 Å³	Chemaxon
Number of Rings	5	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	No	Chemaxon
Ghose Filter	No	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	Yes	Chemaxon

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-001i-0000290000-e2aa17cfbab3fed517a8
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-001i-0000090000-98b02b32c46903e2fee3
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-001i-0000090000-b77d46b9750919efc439
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-001i-9000080000-5a2c72fdfb93f58fd972
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-00lr-0402290000-db23c0fafa675e13cab8
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-001r-3110090000-9aa560dccb18e1bf36fb

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å²)	Source type	Source
[M-H]-	217.84755	predicted	DeepCCS 1.0 (2019)
[M+H]+	220.2431	predicted	DeepCCS 1.0 (2019)
[M+Na]+	226.41927	predicted	DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models

Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.

Learn more

Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.

Learn more

Details1. ALK tyrosine kinase receptor

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Inhibitor

General Function: Transmembrane receptor protein tyrosine kinase activity
Specific Function: Neuronal orphan receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis a...
Gene Name: ALK
Uniprot ID: Q9UM73
Uniprot Name: ALK tyrosine kinase receptor
Molecular Weight: 176440.535 Da

References

Ceccon M, Mologni L, Bisson W, Scapozza L, Gambacorti-Passerini C: Crizotinib-resistant NPM-ALK mutants confer differential sensitivity to unrelated Alk inhibitors. Mol Cancer Res. 2013 Feb;11(2):122-32. doi: 10.1158/1541-7786.MCR-12-0569. Epub 2012 Dec 13. [Article]
Iragavarapu C, Mustafa M, Akinleye A, Furqan M, Mittal V, Cang S, Liu D: Novel ALK inhibitors in clinical use and development. J Hematol Oncol. 2015 Feb 27;8:17. doi: 10.1186/s13045-015-0122-8. [Article]
Markham A: Brigatinib: First Global Approval. Drugs. 2017 Jul;77(10):1131-1135. doi: 10.1007/s40265-017-0776-3. [Article]

Details2. Epidermal growth factor receptor

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Inhibitor

General Function: Ubiquitin protein ligase binding
Specific Function: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TG...
Gene Name: EGFR
Uniprot ID: P00533
Uniprot Name: Epidermal growth factor receptor
Molecular Weight: 134276.185 Da

References

Ceccon M, Mologni L, Bisson W, Scapozza L, Gambacorti-Passerini C: Crizotinib-resistant NPM-ALK mutants confer differential sensitivity to unrelated Alk inhibitors. Mol Cancer Res. 2013 Feb;11(2):122-32. doi: 10.1158/1541-7786.MCR-12-0569. Epub 2012 Dec 13. [Article]
Iragavarapu C, Mustafa M, Akinleye A, Furqan M, Mittal V, Cang S, Liu D: Novel ALK inhibitors in clinical use and development. J Hematol Oncol. 2015 Feb 27;8:17. doi: 10.1186/s13045-015-0122-8. [Article]
Markham A: Brigatinib: First Global Approval. Drugs. 2017 Jul;77(10):1131-1135. doi: 10.1007/s40265-017-0776-3. [Article]

Details3. Tyrosine-protein kinase ABL1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Syntaxin binding
Specific Function: Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility a...
Gene Name: ABL1
Uniprot ID: P00519
Uniprot Name: Tyrosine-protein kinase ABL1
Molecular Weight: 122871.435 Da

References

Markham A: Brigatinib: First Global Approval. Drugs. 2017 Jul;77(10):1131-1135. doi: 10.1007/s40265-017-0776-3. [Article]
Ceccon M, Mologni L, Bisson W, Scapozza L, Gambacorti-Passerini C: Crizotinib-resistant NPM-ALK mutants confer differential sensitivity to unrelated Alk inhibitors. Mol Cancer Res. 2013 Feb;11(2):122-32. doi: 10.1158/1541-7786.MCR-12-0569. Epub 2012 Dec 13. [Article]

Details4. Insulin-like growth factor 1 receptor

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Protein tyrosine kinase activity
Specific Function: Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involv...
Gene Name: IGF1R
Uniprot ID: P08069
Uniprot Name: Insulin-like growth factor 1 receptor
Molecular Weight: 154791.73 Da

References

Ceccon M, Mologni L, Bisson W, Scapozza L, Gambacorti-Passerini C: Crizotinib-resistant NPM-ALK mutants confer differential sensitivity to unrelated Alk inhibitors. Mol Cancer Res. 2013 Feb;11(2):122-32. doi: 10.1158/1541-7786.MCR-12-0569. Epub 2012 Dec 13. [Article]
Markham A: Brigatinib: First Global Approval. Drugs. 2017 Jul;77(10):1131-1135. doi: 10.1007/s40265-017-0776-3. [Article]

Details5. Receptor-type tyrosine-protein kinase FLT3

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Vascular endothelial growth factor-activated receptor activity
Specific Function: Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells...
Gene Name: FLT3
Uniprot ID: P36888
Uniprot Name: Receptor-type tyrosine-protein kinase FLT3
Molecular Weight: 112902.51 Da

References

Ceccon M, Mologni L, Bisson W, Scapozza L, Gambacorti-Passerini C: Crizotinib-resistant NPM-ALK mutants confer differential sensitivity to unrelated Alk inhibitors. Mol Cancer Res. 2013 Feb;11(2):122-32. doi: 10.1158/1541-7786.MCR-12-0569. Epub 2012 Dec 13. [Article]
Markham A: Brigatinib: First Global Approval. Drugs. 2017 Jul;77(10):1131-1135. doi: 10.1007/s40265-017-0776-3. [Article]

Details6. Insulin receptor

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Binding

General Function: Receptor signaling protein tyrosine kinase activity
Specific Function: Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (...
Gene Name: INSR
Uniprot ID: P06213
Uniprot Name: Insulin receptor
Molecular Weight: 156331.465 Da

References

FDA Reports [Link]

Details7. Hepatocyte growth factor receptor

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Protein tyrosine kinase activity
Specific Function: Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including...
Gene Name: MET
Uniprot ID: P08581
Uniprot Name: Hepatocyte growth factor receptor
Molecular Weight: 155540.035 Da

References

FDA Reports [Link]

Details8. Receptor tyrosine-protein kinase erbB-4

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Transmembrane receptor protein tyrosine kinase activity
Specific Function: Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mamma...
Gene Name: ERBB4
Uniprot ID: Q15303
Uniprot Name: Receptor tyrosine-protein kinase erbB-4
Molecular Weight: 146806.865 Da

References

FDA Reports [Link]

Details9. Receptor tyrosine-protein kinase erbB-2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Transmembrane signaling receptor activity
Specific Function: Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, alt...
Gene Name: ERBB2
Uniprot ID: P04626
Uniprot Name: Receptor tyrosine-protein kinase erbB-2
Molecular Weight: 137909.27 Da

References

FDA Reports [Link]

Enzymes

Details1. Cytochrome P450 2C8

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Steroid hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP2C8
Uniprot ID: P10632
Uniprot Name: Cytochrome P450 2C8
Molecular Weight: 55824.275 Da

References

Markham A: Brigatinib: First Global Approval. Drugs. 2017 Jul;77(10):1131-1135. doi: 10.1007/s40265-017-0776-3. [Article]
FDA Reports [Link]

Details2. Cytochrome P450 3A4

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Vitamin d3 25-hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name: CYP3A4
Uniprot ID: P08684
Uniprot Name: Cytochrome P450 3A4
Molecular Weight: 57342.67 Da

References

Markham A: Brigatinib: First Global Approval. Drugs. 2017 Jul;77(10):1131-1135. doi: 10.1007/s40265-017-0776-3. [Article]
FDA Reports [Link]

Details3. Cytochrome P450 3A Subfamily (Protein Group)

Kind: Protein group
Organism: Humans
Pharmacological action: Unknown
Actions: Inducer

General Function: Vitamin d3 25-hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...

Components:

Name	UniProt ID
Cytochrome P450 3A4	P08684
Cytochrome P450 3A43	Q9HB55
Cytochrome P450 3A5	P20815
Cytochrome P450 3A7	P24462

Transporters

Details1. ATP-binding cassette sub-family B member 5

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate
Inhibitor

General Function: Efflux transmembrane transporter activity
Specific Function: Drug efflux transporter present in a number of stem cells that acts as a regulator of cellular differentiation. Able to mediate efflux from cells of the rhodamine dye and of the therapeutic drug do...
Gene Name: ABCB5
Uniprot ID: Q2M3G0
Uniprot Name: ATP-binding cassette sub-family B member 5
Molecular Weight: 138639.48 Da

References

FDA Reports [Link]

Details2. ATP-binding cassette sub-family G member 2

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate
Inhibitor

General Function: Xenobiotic-transporting atpase activity
Specific Function: High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name: ABCG2
Uniprot ID: Q9UNQ0
Uniprot Name: ATP-binding cassette sub-family G member 2
Molecular Weight: 72313.47 Da

References

FDA Reports [Link]

Details3. Solute carrier family 22 member 1

Kind: Protein
Organism: Humans
Pharmacological action: No

General Function: Secondary active organic cation transmembrane transporter activity
Specific Function: Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name: SLC22A1
Uniprot ID: O15245
Uniprot Name: Solute carrier family 22 member 1
Molecular Weight: 61153.345 Da

Details4. Multidrug and toxin extrusion protein 1

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Inhibitor

General Function: Monovalent cation:proton antiporter activity
Specific Function: Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
Gene Name: SLC47A1
Uniprot ID: Q96FL8
Uniprot Name: Multidrug and toxin extrusion protein 1
Molecular Weight: 61921.585 Da

References

Brigatinib [Link]
BRIGATINIB FDA LABEL [File]

Details5. Multidrug and toxin extrusion protein 2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor
Curator comments: Data is based on in vitro studies.

General Function: Drug transmembrane transporter activity
Specific Function: Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acy...
Gene Name: SLC47A2
Uniprot ID: Q86VL8
Uniprot Name: Multidrug and toxin extrusion protein 2
Molecular Weight: 65083.915 Da

References

Brigatinib FDA label [File]

Drug created at October 20, 2016 21:46 / Updated at February 20, 2024 23:54

Brigatinib

Identification

Structure for Brigatinib (DB12267)

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Collision Cross Sections (CCS)

Targets

References

References

References

References

References

References

References

References

References

Enzymes

References

References

Components:

Transporters

References

References

References

References