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Details

Stereochemistry ACHIRAL
Molecular Formula C29H39ClN7O2P
Molecular Weight 584.092
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BRIGATINIB

SMILES

COC1=C(NC2=NC=C(Cl)C(NC3=CC=CC=C3P(C)(C)=O)=N2)C=CC(=C1)N4CCC(CC4)N5CCN(C)CC5

InChI

InChIKey=AILRADAXUVEEIR-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Molecular Formula C29H39ClN7O2P
Molecular Weight 584.092
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Brigatinib (AP26113) is an investigational, targeted cancer medicine discovered internally at ARIAD Pharmaceuticals, Inc. Brigatinib has exhibited activity as a potent dual inhibitor of anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR). It is in development for the treatment of patients with anaplastic lymphoma kinase positive (ALK+) non-small cell cancer (NSCLC) whose disease is resistant to crizotinib. Brigatinib is currently being evaluated in the global Phase 2 ALTA (ALK in Lung Cancer Trial of AP26113) trial that is anticipated to form the basis for its initial regulatory review. ARIAD has also initiated the Phase 3 ALTA 1L trial to assess the efficacy of brigatinib in comparison to crizotinib. Brigatinib was granted orphan drug designation by the U.S. Food and Drug Administration (FDA) in May 2016 for the treatment of certain subtypes of non-small cell lung cancer (NSCLC). The designation is for anaplastic lymphoma kinase-positive (ALK+), c-ros 1 oncogene positive (ROS1+), or epidermal growth factor receptor positive (EGFR+) non-small cell lung cancer (NSCLC). Brigatinib received breakthrough therapy designation from the FDA in October 2014 for the treatment of patients with ALK+ NSCLC whose disease is resistant to crizotinib. Both designations were based on results from an ongoing Phase 1/2 trial that showed anti-tumor activity of brigatinib in patients with ALK+ NSCLC, including patients with active brain metastases.

CNS Activity

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
10.0 nM [IC50]
Conditions
PubMed

PubMed

TitleDatePubMed
Brigatinib, an anaplastic lymphoma kinase inhibitor, abrogates activity and growth in ALK-positive neuroblastoma cells, Drosophila and mice.
2016 May 17
Patents

Patents

Sample Use Guides

In Vivo Use Guide
90 mg tablet, taken orally once daily,continuously in a 28-day cycle
Route of Administration: Oral
In Vitro Use Guide
Brigatinib inhibited ALK phosphorylation in a dose-dependent manner, and at 50 nM brigatinib, phosphorylation of ALK was abolished in ALK addicted neuroblastoma lines
Substance Class Chemical
Created
by admin
on Mon Oct 21 21:30:08 UTC 2019
Edited
by admin
on Mon Oct 21 21:30:08 UTC 2019
Record UNII
HYW8DB273J
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BRIGATINIB
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
BRIGATINIB [WHO-DD]
Common Name English
AP26113
Code English
5-CHLORO-N4-(2-(DIMETHYLPHOSPHORYL)PHENYL)-N2-(2-METHOXY-4-(4-(4-METHYLPIPERAZIN-1- YL)PIPERIDIN-1-YL)PHENYL)PYRIMIDINE-2,4-DIAMINE
Systematic Name English
BRIGATINIB [USAN]
Common Name English
(2-((5-CHLORO-2-((2-METHOXY-4-(4-(4-METHYLPIPERAZIN-1-YL)PIPERIDIN-1-YL)PHENYL)AMINO)PYRIMIDIN-4-YL)AMINO)PHENYL)DIMETHYL-,.DELTA.5-PHOSPHANONE
Systematic Name English
2,4-PYRIMIDINEDIAMINE, 5-CHLORO-N4-(2-(DIMETHYLPHOSPHINYL)PHENYL)-N2-(2-METHOXY-4-(4-(4-METHYL-1-PIPERAZINYL)-1-PIPERIDINYL)PHENYL)-
Systematic Name English
ALUNBRIG
Brand Name English
AP-26113
Code English
BRIGATINIB [INN]
Common Name English
Classification Tree Code System Code
WHO-ATC L01XE43
Created by admin on Mon Oct 21 21:30:08 UTC 2019 , Edited by admin on Mon Oct 21 21:30:08 UTC 2019
NCI_THESAURUS C129825
Created by admin on Mon Oct 21 21:30:08 UTC 2019 , Edited by admin on Mon Oct 21 21:30:08 UTC 2019
FDA ORPHAN DRUG 505415
Created by admin on Mon Oct 21 21:30:08 UTC 2019 , Edited by admin on Mon Oct 21 21:30:08 UTC 2019
NDF-RT N0000175605
Created by admin on Mon Oct 21 21:30:08 UTC 2019 , Edited by admin on Mon Oct 21 21:30:08 UTC 2019
NCI_THESAURUS C1967
Created by admin on Mon Oct 21 21:30:08 UTC 2019 , Edited by admin on Mon Oct 21 21:30:08 UTC 2019
Code System Code Type Description
ChEMBL
CHEMBL3545311
Created by admin on Mon Oct 21 21:30:08 UTC 2019 , Edited by admin on Mon Oct 21 21:30:08 UTC 2019
PRIMARY
CAS
1197953-54-0
Created by admin on Mon Oct 21 21:30:08 UTC 2019 , Edited by admin on Mon Oct 21 21:30:08 UTC 2019
PRIMARY
NCI_THESAURUS
C98831
Created by admin on Mon Oct 21 21:30:08 UTC 2019 , Edited by admin on Mon Oct 21 21:30:08 UTC 2019
PRIMARY
WIKIPEDIA
Brigatinib
Created by admin on Mon Oct 21 21:30:08 UTC 2019 , Edited by admin on Mon Oct 21 21:30:08 UTC 2019
PRIMARY
RXCUI
1921217
Created by admin on Mon Oct 21 21:30:08 UTC 2019 , Edited by admin on Mon Oct 21 21:30:08 UTC 2019
PRIMARY
PUBCHEM
68165256
Created by admin on Mon Oct 21 21:30:08 UTC 2019 , Edited by admin on Mon Oct 21 21:30:08 UTC 2019
PRIMARY
INN
10085
Created by admin on Mon Oct 21 21:30:08 UTC 2019 , Edited by admin on Mon Oct 21 21:30:08 UTC 2019
PRIMARY
EVMPD
SUB184911
Created by admin on Mon Oct 21 21:30:08 UTC 2019 , Edited by admin on Mon Oct 21 21:30:08 UTC 2019
PRIMARY
Related Record Type Details
TRANSPORTER -> SUBSTRATE
TARGET -> INHIBITOR
INHIBITOR
IC50
TRANSPORTER -> SUBSTRATE
TARGET -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
FECAL
EXCRETED UNCHANGED
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
INHIBITOR
IC50
BINDER->LIGAND
BINDING
Related Record Type Details
METABOLITE -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
Volume of Distribution