Brigatinib (AP26113)

For research use only.

Catalog No.S8229

12 publications

Brigatinib (AP26113) Chemical Structure

CAS No. 1197953-54-0

Brigatinib (AP26113) is a potent and selective ALK (IC50, 0.6 nM) and ROS1 (IC50, 0.9 nM) inhibitor. It also inhibits IGF-1R, FLT3, and mutant variants of FLT3 (D835Y) and EGFR with lower potentcy.

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Selleck's Brigatinib (AP26113) has been cited by 12 publications

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  • Immunoblotting analysis of H3122 and H3122-CER cells showing that brigatinib did not inhibit EGFR phosphorylation (p-EGFR). Total EGFR (t-EGFR) is also shown. Actin was used as a loading control. The cells were treated with brigatinib for 2 hours.

    Mol Cancer Res, 2017, 15(1):106-114. Brigatinib (AP26113) purchased from Selleck.

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Choose Selective ALK Inhibitors

Biological Activity

Description Brigatinib (AP26113) is a potent and selective ALK (IC50, 0.6 nM) and ROS1 (IC50, 0.9 nM) inhibitor. It also inhibits IGF-1R, FLT3, and mutant variants of FLT3 (D835Y) and EGFR with lower potentcy.
Targets
ALK [1]
(Cell-free assay)		 ROS1 [1]
(Cell-free assay)		 FLT3 [1]
(Cell-free assay)		 IGF1R [1]
(Cell-free assay)		 EGFR(C797S/del19) [2]
(cell-based)
0.37 nM 1.9 nM 2.1 nM 24.9 nM 39.9 nM
In vitro

Beyond ALK, IGF1R, and InsR, brigatinib also potently inhibits FLT3 and ROS1 with IC50 values of 2.1 and 1.9 nM, respectively. It does not show significant activity toward c-Met or Ron up to 1 μM[1]. Brigatinib overcomes the resistance of EGFR-triple-mutant and the activity depends on ATP-competitive manner with less affection to wild-type EGFR[2].
Assay
Methods Test Index PMID
Western blot
pEGFR / EGFR / pAkt / Akt / pERK / ERK / pS6 / S6; 

PubMed: 28287083     


Ba/F3 cells expressing T790M/del19 (d) or C797S/T790M/del19 (e) were treated with the indicated concentrations of brigatinib, AP26113 analog, TAE684, ceritinib or ASP3026 for 6 h. Phosphorylation of EGFR and its downstream signals were evaluated by wester䲧疝Ỵ疞㧀疜膉痘 瘿�෋ᾰƌ෋à 

pALK / ALK; 

PubMed: 21502504     


Suppression of ALK signaling by AP26113 in resistant H3122 CR cells. H3122 parental and resistant cells were exposed to increasing concentrations of AP26113 for 6 h. Cell lysates were immunoblotted to detect the indicated proteins.

pROS1 / ROS1 / pSTAT3 / STAT3 ; 

PubMed: 25351743     


Inhibition of phospho-ROS1 by various ALK inhibitors in Ba/F3 models. CD74-ROS1 expressing Ba/F3 cells were exposed to increasing concentrations of crizotinib, ceritinib, AP26113, or ASP3026 for 3 h. Cell lysates were immunoblotted to detect the indicated䲧疝Ỵ疞㧀

28287083 21502504 25351743
Growth inhibition assay
Cell viability ; 

PubMed: 25351743     


(A) Ba/F3 cells expressing CD74-ROS1 (clone #6) were seeded in 96 well-plates and treated with indicated concentration of crizotinib, ceritinib, AP26113, ASP3026, or alectinib for 72 h. Cell viability was analyzed using the CellTiter-Glo assay. (B) IC50 v䲧疝Ỵ疞㧀疜膉痘 瘿뾠ՂᾰƌՂĀ 㺣痖帉痖Ѐ瑖堘𢡄빢᎒ՂĀ鑸᎒彿堙奋堙巫堙᎒ﻺ᎒彿堙ﻮ᎒塚堙ﻺ᎒ꍈ堞빢᎒學堙漸堞圔堙빢᎒圞堙圭堙𢡄玚Wᾰƌ ᾰƌ戤瘯Ɖ⟸෕䐺痖暼瘿⟸෕ᾰƌ ⟸෕Ð㺣痖⟸෕€𢡄⟼෕€䀷痗⟼෕౴⟼෕㵶痗⟼෕뺖᎒泌Itemｾ᎒Count﫨呂⠬෕猴፲⟼෕፲씢痗猸፲髸莤䥷堙᎒ｾ᎒�堞ﻮ᎒፲露𢡄堚ў齃礤v�堞ﻮ᎒猢

25351743
In vivo Mouse PK parameters for Brigatinib following oral dosing (10 mg/kg): Cmax=448 ng/mL,t1/2=5.8 h. And in CD rats, after dosing at 3 mg/kg i.v, CL=0.46 L/(h·kg), t1/2=4.8 h, Vss=7.8 L/kg; Dosed at 10 mg/kg p.o, Cmax=305 ng/mL, tmax=4 h, t1/2=3.4 h， F%=52. Brigatinib demonstrates dose-dependent antitumor activity[1]. Brigatinib demonstrates growth inhibition activity in PC9 triple-mutant xenograft model and in combination with anti-EGFR antibody to potentiate the efficacy both in vitro and in vivo as shown in first-generation EGFR-TKI-resistant patients[2].

Protocol

Cell Research:

[1]
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  • Cell lines: U937 cells, Karpas-299 cells, H3122 cells
  • Concentrations: --
  • Incubation Time: 72 h
  • Method:

    All cell lines were used within 20 passages of the initial thaw. Following inhibitor treatment for 72 h, cell growth was assessed to determine the concentration that causes 50% inhibition of cell viability (IC50).


    (Only for Reference)
Animal Research:

[1]
- Collapse
  • Animal Models: female CD rats
  • Dosages: 10 mg/kg(p.o); 2 mg/kg(i.v)
  • Administration: p.o, i.v
    (Only for Reference)

Solubility (25°C)

In vitro Ethanol 43 mg/mL warmed (73.61 mM)
DMSO 1 mg/mL warmed (1.71 mM)
Water Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 584.09
Formula

C29H39ClN7O2P
CAS No. 1197953-54-0
Storage powder
in solvent
Synonyms N/A
Smiles CN1CCN(CC1)C2CCN(CC2)C3=CC(=C(C=C3)NC4=NC=C(C(=N4)NC5=CC=CC=C5P(=O)(C)C)Cl)OC

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04260009 Withdrawn Drug: Brigatinib|Drug: Brigatinib AAF Anaplastic Lymphoma Kinase Positive (ALK +) Anaplastic Large Cell Lymphoma|Inflammatory Myofibroblastic Tumors|Solid Tumors Takeda September 1 2020 Phase 1|Phase 2
NCT04111705 Recruiting Drug: Lorlatinib Non Small Cell Lung Cancer Metastatic Intergroupe Francophone de Cancerologie Thoracique August 2020 Phase 2
NCT04005144 Recruiting Drug: Binimetinib|Drug: Brigatinib ALK Gene Rearrangement|Lung Non-Small Cell Carcinoma|Progressive Disease|ROS1 Gene Rearrangement|Stage IIIB Lung Cancer|Stage IIIC Lung Cancer|Stage IV Lung Cancer|Stage IVA Lung Cancer|Stage IVB Lung Cancer University of California San Francisco|Takeda|Array BioPharma December 6 2019 Phase 1
NCT03410108 Active not recruiting Drug: Brigatinib ALK-positive Advanced NSCLC Takeda January 29 2018 Phase 2
NCT02094573 Completed Drug: Brigatinib Carcinoma Non-Small-Cell Lung Ariad Pharmaceuticals|Takeda June 4 2014 Phase 2
NCT01449461 Completed Drug: Brigatinib Lymphoma Large-Cell Anaplastic|Carcinoma Non-Small-Cell Lung Ariad Pharmaceuticals|Takeda September 20 2011 Phase 1|Phase 2

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ALK Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID