Brigatinib

Summary

Brigatinib (CHEMBL3545311) is an approved small molecule (ATC L01ED04) targeting EGFR, INSR, and IGF1R; indicated across 5 conditions including non-small cell lung carcinoma and neoplasm.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L01ED04
• Targets: 4 (EGFR, INSR, IGF1R…)
• Indications: 5 conditions
• Clinical trials: 35
• Chemistry: 584.1 Da · C29H39ClN7O2P

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3545311
Name	Brigatinib
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	68165256
ATC	L01ED04
Molecular formula	C29H39ClN7O2P
Molecular weight	584.1
InChIKey	AILRADAXUVEEIR-UHFFFAOYSA-N

SMILES: CN1CCN(CC1)C2CCN(CC2)C3=CC(=C(C=C3)NC4=NC=C(C(=N4)NC5=CC=CC=C5P(=O)(C)C)Cl)OC

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

Also known as: Alunbrig, Ap-26113, AP-26113, AP26113, Brigatinib, AP 26113, BRIGATINIB, ALUNBRIG, BRIGATINIBAP-26113AP26113CS-4278, BRIGATINIB (AP-26113), BRIGATINIB (AP26113), brigatinib

Patent coverage: 2,393 distinct patent families (5,634 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 5,494 (98%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
EGFR	epidermal growth factor receptor	Inhibition	6.89	17.5%	P00533
INSR	Insulin receptor	Inhibition	6.71	0.8%	P06213
IGF1R	Insulin-like growth factor I receptor	Inhibition	7.61	19%	P08069
ALK	ALK receptor tyrosine kinase	Inhibition	10.05	0.8%	Q9UM73

Broader ChEMBL bioactivity targets: 78 (assay-derived). Sample: Leucine-rich repeat serine/threonine-protein kinase 2, Receptor tyrosine-protein kinase erbB-2, Tyrosine-protein kinase Fyn, Macrophage colony-stimulating factor 1 receptor, Tyrosine-protein kinase ABL1, Mast/stem cell growth factor receptor Kit, Vascular endothelial growth factor receptor 3, Insulin-like growth factor 1 receptor, Receptor-type tyrosine-protein kinase FLT3, Insulin receptor.

Bioactivity

ChEMBL activities: 226 potent at pChembl ≥ 5 of 227 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ALK	9.43	IC50	0.37	nM	CHEMBL_ACT_16635886
ALK	9.22	IC50	0.6	nM	CHEMBL_ACT_26307828
ALK	9.22	IC50	0.6	nM	CHEMBL_ACT_26307829
EGFR	9.15	IC50	0.7	nM	CHEMBL_ACT_24726362
EGFR	9.09	IC50	0.82	nM	CHEMBL_ACT_24741548
EGFR	9.09	IC50	0.82	nM	CHEMBL_ACT_25481284
EGFR	9	IC50	1	nM	CHEMBL_ACT_19315819
EGFR	9	IC50	1	nM	CHEMBL_ACT_19315833
ALK	8.92	IC50	1.2	nM	CHEMBL_ACT_24360263
EGFR	8.89	IC50	1.3	nM	CHEMBL_ACT_25098110
FER	8.89	IC50	1.3	nM	CHEMBL_ACT_26307842
ALK	8.85	IC50	1.4	nM	CHEMBL_ACT_26307830
EGFR	8.82	IC50	1.5	nM	CHEMBL_ACT_20690047
EGFR	8.82	IC50	1.5	nM	CHEMBL_ACT_20690065
FLT3	8.82	IC50	1.5	nM	CHEMBL_ACT_26307835
EGFR	8.82	IC50	1.5	nM	CHEMBL_ACT_26307837
ALK	8.82	IC50	1.5	nM	CHEMBL_ACT_26308063
EGFR	8.8	IC50	1.6	nM	CHEMBL_ACT_25098072
ALK	8.77	IC50	1.7	nM	CHEMBL_ACT_22395837
ALK	8.77	IC50	1.7	nM	CHEMBL_ACT_25016245
ALK	8.77	IC50	1.7	nM	CHEMBL_ACT_26307843
ROS1	8.72	IC50	1.9	nM	CHEMBL_ACT_16636126
ROS1	8.72	IC50	1.9	nM	CHEMBL_ACT_26307833
EGFR	8.7	IC50	2	nM	CHEMBL_ACT_28620149
FLT3	8.68	IC50	2.1	nM	CHEMBL_ACT_16636125
FLT3	8.68	IC50	2.1	nM	CHEMBL_ACT_26307834
ALK	8.68	IC50	2.1	nM	CHEMBL_ACT_26308059
EGFR	8.6	IC50	2.5	nM	CHEMBL_ACT_20690056
EGFR	8.54	IC50	2.9	nM	CHEMBL_ACT_29243192
EGFR	8.52	IC50	3	nM	CHEMBL_ACT_19132114

Target pathways

Aggregated over 4 target gene(s): EGFR, INSR, IGF1R, ALK.

Top Reactome pathways

64 total, by targets touching each:

Pathway	Targets	Genes
PIP3 activates AKT signaling	2	EGFR, INSR
Signal Transduction	2	ALK, INSR
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	2	EGFR, INSR
Signaling by Receptor Tyrosine Kinases	2	ALK, INSR
Extra-nuclear estrogen signaling	2	EGFR, IGF1R
Respiratory syncytial virus (RSV) attachment and entry	2	EGFR, IGF1R
Signaling by ERBB2	1	EGFR
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	1	EGFR
Signaling by ERBB4	1	EGFR
SHC1 events in ERBB2 signaling	1	EGFR
PLCG1 events in ERBB2 signaling	1	EGFR
Disease	1	ALK
Signaling by EGFR	1	EGFR
GRB2 events in EGFR signaling	1	EGFR
GAB1 signalosome	1	EGFR
SHC1 events in EGFR signaling	1	EGFR
EGFR downregulation	1	EGFR
GRB2 events in ERBB2 signaling	1	EGFR
PI3K events in ERBB2 signaling	1	EGFR
Negative regulation of the PI3K/AKT network	1	INSR
Signaling by ALK	1	ALK
EGFR interacts with phospholipase C-gamma	1	EGFR
EGFR Transactivation by Gastrin	1	EGFR
Constitutive Signaling by Aberrant PI3K in Cancer	1	EGFR
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)	1	IGF1R
IRS-related events triggered by IGF1R	1	IGF1R
SHC-related events triggered by IGF1R	1	IGF1R
Signal transduction by L1	1	EGFR
Constitutive Signaling by EGFRvIII	1	EGFR
Inhibition of Signaling by Overexpressed EGFR	1	EGFR

Dominant GO biological processes

GO term	Targets
protein phosphorylation	4
cell surface receptor protein tyrosine kinase signaling pathway	4
signal transduction	3
positive regulation of cell population proliferation	3
positive regulation of cell migration	3
positive regulation of MAPK cascade	3
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	3
protein autophosphorylation	3
negative regulation of apoptotic process	2
phosphatidylinositol 3-kinase/protein kinase B signal transduction	2
receptor-mediated endocytosis	2
epidermis development	2
regulation of cell population proliferation	2
symbiont entry into host cell	2
cellular response to growth factor stimulus	2

Indications & clinical

Indications

5 indications (2 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
non-small cell lung carcinoma	4	MONDO:0005233	EFO:0003060
neoplasm	4	MONDO:0005070	EFO:0000616
carcinoma	3	MONDO:0004993	EFO:0000313
lung neoplasm	3	MONDO:0021117	MONDO:0008903
anaplastic large cell lymphoma	2	MONDO:0020325	EFO:0003032

Clinical trials

Total trials: 35.

Phase distribution

Phase	Trials
PHASE2	18
Not specified	7
PHASE1	5
PHASE1/PHASE2	3
PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02737501	PHASE3	COMPLETED	ALTA-1L Study: A Study of Brigatinib Versus Crizotinib in Anaplastic Lymphoma Kinase Positive (ALK+) Advanced Non-small Cell Lung Cancer (NSCLC) Participants
NCT03596866	PHASE3	COMPLETED	A Study of Brigatinib Compared to Alectinib in Adults With Non-Small-Cell Lung Cancer
NCT04223596	PHASE2	ACTIVE_NOT_RECRUITING	Clinical Utility of Liquid Biopsy in Brigatinib ALK+ Patients
NCT04318938	PHASE2	ACTIVE_NOT_RECRUITING	Advancing Brigatinib Properties in ALK+ NSCLC Patients by Deep Phenotyping
NCT04374305	PHASE2	RECRUITING	Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (INTUITT-NF2)
NCT04925609	PHASE1/PHASE2	RECRUITING	Brigatinib in Pediatric and Young Adult Patients With ALK+ ALCL, IMT or Other Solid Tumors
NCT05200481	PHASE2	ACTIVE_NOT_RECRUITING	Study of Safety and Efficacy of Brigatinib Plus Chemotherapy or Brigatinib Only in Advanced ALK-Positive Lung Cancer (MASTERPROTOCOL ALK)
NCT06813079	PHASE2	NOT_YET_RECRUITING	Using Tumor Models to Determine Treatments
NCT01449461	PHASE1/PHASE2	COMPLETED	A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-Tumor Activity of the Oral Anaplastic Lymphoma Kinase (ALK)/Epidermal Growth Factor Receptor (EGFR) Inhibitor Brigatinib (AP26113)
NCT02094573	PHASE2	COMPLETED	A Study to Evaluate the Efficacy of Brigatinib (AP26113) in Participants With Anaplastic Lymphoma Kinase (ALK)-Positive, Non-small Cell Lung Cancer (NSCLC) Previously Treated With Crizotinib
NCT02706626	PHASE2	TERMINATED	Trial of Brigatinib After Treatment With Next-Generation ALK Inhibitors
NCT03410108	PHASE2	COMPLETED	Phase 2 Study of Brigatinib in Japanese Participants With Anaplastic Lymphoma Kinase (ALK)-Positive Non-Small Cell Lung Cancer (NSCLC)
NCT03535740	PHASE2	COMPLETED	A Study of Brigatinib in Participants With Anaplastic Lymphoma Kinase-Positive (ALK+), Advanced Non-Small-Cell Lung Cancer (NSCLC) Progressed on Alectinib or Ceritinib
NCT03719898	PHASE2	WITHDRAWN	Brigatinib in Relapsed or Refractory ALK-Positive Anaplastic Large Cell Lymphoma
NCT03737994	PHASE2	TERMINATED	Targeted Treatment for ALK Positive Patients Who Have Previously Been Treated for Non-squamous Non-small Cell Lung Cancer
NCT03868423	PHASE2	WITHDRAWN	Brigatinib in Treating Patients With ALK and ROS1 Gene Alterations and Locally Advanced or Metastatic Solid Cancers
NCT04074993	PHASE2	UNKNOWN	Brigatinib in ALK-positive NSCLC Identified Via Blood-based Assays
NCT04260009	PHASE1/PHASE2	WITHDRAWN	Pharmacokinetics, Safety, and Efficacy of Brigatinib Monotherapy in Pediatric and Young Adult Participants With ALK+ Anaplastic Large Cell Lymphoma, Inflammatory Myofibroblastic Tumors or Other Solid Tumors
NCT04591431	PHASE2	UNKNOWN	The Rome Trial From Histology to Target: the Road to Personalize Target Therapy and Immunotherapy
NCT04634110	PHASE2	TERMINATED	Brigatinib Before Brain Irradiation Trial (B3i Trial)
NCT05361564	PHASE2	UNKNOWN	A Window of Opportunity Study for Investigating Drug Tolerant Persister (DTP) to Preoperative Brigatinib in Resectable Non-small Cell Lung Cancer (NSCLC) Harboring ALK Fusions.
NCT05718297	PHASE2	WITHDRAWN	Brigatinib Post Definitive Chemo-radiotherapy in Patients with ALK-fusion Non-small Cell Lung Cancer
NCT06522360	PHASE2	WITHDRAWN	Brigatinib Plus Chemotherapy or Local Consolidation Therapy in ALK Positive Advanced Non-small Cell Lung Cancer (BrightStar-2)
NCT03707938	PHASE1	ACTIVE_NOT_RECRUITING	Local Consolidative Therapy and Brigatinib in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer
NCT04227028	PHASE1	ACTIVE_NOT_RECRUITING	Brigatinib and Bevacizumab for the Treatment of ALK-Rearranged Locally Advanced, Metastatic, or Recurrent NSCLC
NCT03420742	PHASE1	COMPLETED	A Phase 1 Drug-Drug Interaction Study Between Brigatinib and the CYP3A Substrate, Midazolam, in Participants With ALK-Positive or ROS1-Positive Solid Tumors
NCT04005144	PHASE1	TERMINATED	Brigatinib and Binimetinib in Treating Patients With Stage IIIB-IV ALK or ROS1-Rearranged Non-small Cell Lung Cancer
NCT06132867	PHASE1	COMPLETED	A Study to Compare the Relative Bioavailability of Brigatinib When Swallowed as a Solution Versus When Swallowed as a Tablet in Healthy Adults
NCT05100069	Not specified	RECRUITING	Survey of Brigatinib Used To Treat People With Non-Small Cell Lung Cancer
NCT05721950	Not specified	ACTIVE_NOT_RECRUITING	A Study to Learn About Brigatinib Treatment Information Available in Chinese Participants With Non-Small-cell Lung Cancer (NSCLC)
NCT06532149	Not specified	RECRUITING	ERectile Dysfunctions, gOnadotoxicity and Sexual Health Assessment in Men With Lung Cancer
NCT02784158	Not specified	NO_LONGER_AVAILABLE	An Expanded Access Study of Brigatinib for Patients With ALK-positive Advanced Non-Small Cell Lung Cancer
NCT03546894	Not specified	COMPLETED	A Study to Determine Progression-free Survival (PFS) and Evaluate Participant Experience for Participants With Metastatic Anaplastic Lymphoma Kinase-positive (ALK+) Non-Small Cell Lung Cancer (NSCLC) Treated With Anaplastic Lymphoma Kinase (ALK) Inhibitors
NCT04647110	Not specified	COMPLETED	Real-world Therapy of ALK-positive NSCLC in Sweden: the Sequencing of ALK Tyrosine Kinase Inhibitor Drugs and Their Therapeutic Outcomes Based on Data From National Registers.
NCT05834348	Not specified	COMPLETED	A Study to Learn About the Effectiveness of Cancer Medicines in Patients With Metastatic Non-small Cell Lung Cancer in Norway.

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

180 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
AFATINIB	ChEMBL + PubChem	Phase 4 (approved)	ALK, EGFR, IGF1R, INSR
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	ALK, EGFR, IGF1R, INSR
GEFITINIB	ChEMBL + PubChem	Phase 4 (approved)	ALK, EGFR, IGF1R, INSR
Pazopanib	ChEMBL + PubChem	Phase 4 (approved)	ALK, EGFR, IGF1R, INSR
SELUMETINIB	ChEMBL + PubChem	Phase 4 (approved)	ALK, EGFR, IGF1R, INSR
CERITINIB	ChEMBL	Phase 4 (approved)	ALK, EGFR, IGF1R, INSR
FEDRATINIB	ChEMBL	Phase 4 (approved)	ALK, EGFR, IGF1R, INSR
SUNITINIB	ChEMBL	Phase 4 (approved)	ALK, EGFR, IGF1R, INSR
LESTAURTINIB	ChEMBL	Phase 3	ALK, EGFR, IGF1R, INSR
CENISERTIB	ChEMBL	Phase 2	ALK, EGFR, IGF1R, INSR
FORETINIB	ChEMBL	Phase 2	ALK, EGFR, IGF1R, INSR
ILORASERTIB	ChEMBL	Phase 2	ALK, EGFR, IGF1R, INSR
R-406	ChEMBL	Phase 2	ALK, EGFR, IGF1R, INSR
TOZASERTIB	ChEMBL	Phase 2	ALK, EGFR, IGF1R, INSR
DACOMITINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, IGF1R, INSR
ENTRECTINIB	ChEMBL	Phase 4 (approved)	ALK, IGF1R, INSR
NINTEDANIB	ChEMBL	Phase 4 (approved)	ALK, IGF1R, INSR
OSIMERTINIB	ChEMBL	Phase 4 (approved)	ALK, EGFR, INSR
DOVITINIB	ChEMBL	Phase 3	ALK, EGFR, INSR
LINIFANIB	ChEMBL	Phase 3	ALK, EGFR, INSR
QUERCETIN	ChEMBL	Phase 3	ALK, EGFR, IGF1R
BMS-754807	ChEMBL	Phase 2	ALK, IGF1R, INSR
ELLAGIC ACID	ChEMBL	Phase 2	EGFR, IGF1R, INSR
OSI-632	ChEMBL	Phase 2	ALK, EGFR, INSR
SU-014813	ChEMBL	Phase 2	ALK, EGFR, INSR
belumosudil	PubChem	Approved	ALK, IGF1R, INSR
Binimetinib	PubChem	Approved	EGFR, IGF1R, INSR
Idelalisib	PubChem	Approved	ALK, IGF1R, INSR
ALECTINIB	ChEMBL	Phase 4 (approved)	ALK, EGFR
BOSUTINIB	ChEMBL	Phase 4 (approved)	ALK, EGFR
ERLOTINIB	ChEMBL	Phase 4 (approved)	ALK, EGFR
GILTERITINIB	ChEMBL	Phase 4 (approved)	ALK, EGFR
INFIGRATINIB	ChEMBL	Phase 4 (approved)	ALK, INSR
LAPATINIB	ChEMBL	Phase 4 (approved)	EGFR, INSR
LORLATINIB	ChEMBL	Phase 4 (approved)	ALK, EGFR
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	ALK, EGFR
NERATINIB	ChEMBL	Phase 4 (approved)	EGFR, INSR
SORAFENIB	ChEMBL	Phase 4 (approved)	EGFR, INSR
VANDETANIB	ChEMBL	Phase 4 (approved)	ALK, EGFR
ALVOCIDIB	ChEMBL	Phase 3	ALK, EGFR
CANERTINIB	ChEMBL	Phase 3	ALK, EGFR
CEDIRANIB	ChEMBL	Phase 3	ALK, EGFR
LINSITINIB	ChEMBL	Phase 3	IGF1R, INSR
ROCILETINIB	ChEMBL	Phase 3	ALK, EGFR
BEMCENTINIB	ChEMBL	Phase 2	ALK, EGFR
BI-2536	ChEMBL	Phase 2	ALK, EGFR
IRUPLINALKIB	ChEMBL	Phase 2	ALK, EGFR
PELITINIB	ChEMBL	Phase 2	ALK, EGFR
TAK-715	ChEMBL	Phase 2	ALK, EGFR
Fostamatinib	PubChem	Approved	IGF1R, INSR
regorafenib	PubChem	Approved	IGF1R, INSR
Trametinib	PubChem	Approved	IGF1R, INSR
ABEMACICLIB	ChEMBL	Phase 4 (approved)	EGFR
ACALABRUTINIB	ChEMBL	Phase 4 (approved)	EGFR
AFATINIB DIMALEATE	ChEMBL	Phase 4 (approved)	EGFR
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	EGFR
AXITINIB	ChEMBL	Phase 4 (approved)	EGFR
BACITRACIN	ChEMBL	Phase 4 (approved)	EGFR
BITHIONOL	ChEMBL	Phase 4 (approved)	EGFR
CABOZANTINIB	ChEMBL	Phase 4 (approved)	EGFR