Brigatinib (AP26113)

Catalog No.S8229

For research use only.

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.

Brigatinib (AP26113) Chemical Structure

CAS No. 1197953-54-0

Selleck's Brigatinib (AP26113) has been cited by 23 publications

Purity & Quality Control

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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)
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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].

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
KARPAS299 M173R2FvfGmycn;sbYZmemG2aY\lJIF{e2G7 MoTGO|IhcHK| NFzleGtCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFHMT{1xd3OrdHn2[UBMSVKSQWOyPVkh[2WubIOgZZN{\XO|ZXSgZZMhemWmdXP0bY9vKGmwIHPlcIwhfmmjYnnsbZR6KG2nYYP1doVlKGGodHXyJFczKGi{czDifUBE\WyuVHn0[ZIhQTZiYYH1[Y92eyCxbnWgd49tfXSrb36gZ4VtdCCycn;sbYZmemG2aX;uJIF{e2G7LDDHTVUxKD1iMD6wNUDPxE1w MnvTQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjdzNES4N|EoRjJ5MUS0PFMyRC:jPh?=
KARPAS299 MXfBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? MUe3NkBpenN? NYHKPHZRSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDBUGsueG:|aYTpeoUhU0GUUFHTNlk6KGOnbHzzJIF{e2W|c3XkJIF{KHKnZIXjeIlwdiCrbjDj[YxtKH[rYXLpcIl1gSCvZXHzeZJm\CCjZoTldkA4OiCqcoOgZpkhS2WubGTpeIVzKDl4IHHxeYVwfXNib37lJJNwdHW2aX;uJINmdGxicILvcIln\XKjdHnvckBie3OjeTygTWM2OCB;IECuNFI6KM7:TT6= NFe0R2I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{G0OFg{OSd-MkexOFQ5OzF:L3G+
Ba/F3 NHfLcZJHfW6ldHnvckBie3OjeR?= NH[3eGM4OiCqcoO= NVn6W4RXUW6qaXLpeIlwdiCxZjDoeY1idiCHR1\SJIRmdDF7L2S3PVBON0N5OUfTJI12fGGwdDDlfJBz\XO|ZXSgbY4hdW:3c3WgRoEwTjNiY3XscJMh[XO|ZYPz[YQh[XNiY3XscEBoem:5dHigbY5pcWKrdHnvckBi\nSncjC3NkBpenNiYomgR4VtdFSrdHXyMWdtdyCjc4PhfUwhT0l3MDC9JFAvODZ5MjFOwG0v MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTF|NkS2OUc,OjlzM{[0OlU9N2F-
BAF3 NXHyd|VuSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= MnnvO|IhcHK| NEfEN5VCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JI1wfXOnIFLBSlMh[2WubIOgbIFz[m:{aX7nJGVITlJiMUnEM3Q4QTCPL1O3PVdUKG23dHHueEBi\nSncjC3NkBpenNiYomgdoV{[Xq3cnnuJIR6\SCkYYPl[EBie3OjeTygTWM2OCB;IECuNlYh|ryPLh?= M1rtb|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyNEK5PVU3Lz5|MESyPVk2PjxxYU6=
BAF3 MVLBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? MYS3NkBpenN? M{LFbWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgcY92e2ViQlHGN{Bk\WyuczDoZZJjd3KrbnegSWdHWiCOOEW4Vk9VPzlyTT;DO|k4WyCvdYThcpQh[W[2ZYKgO|IhcHK|IHL5JJJme2G8dYLpckBlgWViYnHz[YQh[XO|YYmsJGlEPTBiPTCwMlQzKM7:TT6= MmjYQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB2Mkm5OVYoRjNyNEK5PVU3RC:jPh?=
NCI-H1975 NXvFe2UzSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= MorBO|IhcHK| MoTYRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCQQ1mtTFE6PzViY3XscJMhcGG{Yn;ybY5oKEWJRmKgUFg2QFJxVEe5NG0hdXW2YX70JIFnfGW{IEeyJIhzeyCkeTDy[ZNignW{aX6g[JlmKGKjc3XkJIF{e2G7LDDJR|UxKD1iMT6wPUDPxE1w MlPFQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB2Mkm5OVYoRjNyNEK5PVU3RC:jPh?=
U937 M{CxSmFvfGmycn;sbYZmemG2aY\lJIF{e2G7 NGCySVc4OiCqcoO= M1nVZWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iQVzLMY5m\2G2aY\lJHU6OzdiY3XscJMh[XO|ZYPz[YQh[XNicnXkeYN1cW:wIHnuJINmdGxidnnhZoltcXS7IH3lZZN2emWmIHHmeIVzKDd{IHjyd{BjgSCFZXzsWIl1\XJiOU[gZZF2\W:3czDvcoUhe2:udYTpc44h[2WubDDwdo9tcW[ncnH0bY9vKGG|c3H5MEBKSzVyIE2gN{4yQTRizszNMi=> NGC1bWw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{G0OFg{OSd-MkexOFQ5OzF:L3G+
KARPAS299 M4PmdmFvfGm2dX3vdkBie3OjeR?= MkOyOVAhdWdxa3e= Ml\LNVMh\GG7cx?= MXLBcpRqfHWvb4KgZYN1cX[rdImgZYdicW6|dDDoeY1idiCNQWLQRXMzQTliY3XscJMh\XiycnXzd4lv\yCQTWCtRWxMKG[3c3nvckBxem:2ZXnuJJhmdm:pcnHmeIVlKGmwIGPDTWQw[mWrZ3WgcY92e2ViYYPz[ZN{\WRiYYOgeJVud3JicnXndoV{e2mxbjDheEA2OCCvZz;r[{wheG9iYXTtbY5qe3SncnXkJI9v[2ViZHHpcJkh\m:{IEGzJIRigXNuIF7VUGwhRSCQVVzMJO69VS5? M2j3U|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ5MUS0PFMyLz5{N{G0OFg{OTxxYU6=
Assay
Methods Test Index PMID
Western blot pEGFR / EGFR / pAkt / Akt / pERK / ERK / pS6 / S6 ; pALK / ALK ; pROS1 / ROS1 / pSTAT3 / STAT3 28287083 21502504 25351743
Growth inhibition assay Cell viability 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 (from reference)

Cell Research:

[1]

  • 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).

Animal Research:

[1]

  • Animal Models: female CD rats
  • Dosages: 10 mg/kg(p.o); 2 mg/kg(i.v)
  • Administration: p.o, i.v

Solubility (25°C)

In vitro

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

Chemical Information

Molecular Weight 584.09
Formula

C29H39ClN7O2P

CAS No. 1197953-54-0
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CN1CCN(CC1)C2CCN(CC2)C3=CC(=C(C=C3)NC4=NC=C(C(=N4)NC5=CC=CC=C5P(=O)(C)C)Cl)OC

In vivo Formulation Calculator (Clear solution)

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04925609 Not yet recruiting Drug: Brigatinib Anaplastic Large Cell Lymphoma ALK-Positive|Inflammatory Myofibroblastic Tumor|Other Solid Tumor Princess Maxima Center for Pediatric Oncology|Takeda December 2021 Phase 1|Phase 2
NCT04718012 Completed -- Lung Cancer ROS Translocated Centre Hospitalier Intercommunal Creteil March 17 2021 --
NCT04634110 Recruiting Drug: Brigatinib Brain Metastases|Lung Cancer University of Colorado Denver|National Cancer Institute (NCI) November 17 2020 Phase 2
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 5 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 February 25 2020 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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