Name: Brigatinib
Brand: Selleck Chemicals
SKU: S8229
Availability: InStock
Rating: 5 (44 reviews)

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Quality Control

Batch: Purity: 99.91%

99.91

Related Targets	EGFR VEGFR JAK PDGFR FGFR Src HIF FLT FLT3 HER2
Other ALK Products	TAE684 (NVP-TAE684) GSK1838705A Repotrectinib (TPX-0005) AZD3463 AP26113-analog (ALK-IN-1) Ensartinib dihydrochloride ASP3026 HG-14-10-04 X-376 ALK inhibitor 1

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
KARPAS299	Antiproliferative assay		72 hrs	Antiproliferative activity against human ALK-positive KARPAS299 cells assessed as reduction in cell viability measured after 72 hrs by CellTiter 96 aqueous one solution cell proliferation assay, GI50 = 0.01 μM.	27144831
KARPAS299	Antiproliferative assay		72 hrs	Antiproliferative activity against human ALK-positive KARPAS299 cells assessed as reduction in cell viability measured after 72 hrs by CellTiter 96 aqueous one solution cell proliferation assay, IC50 = 0.029 μM.	27144831
Ba/F3	Function assay		72 hrs	Inhibition of human EGFR del19/T790M/C797S mutant expressed in mouse Ba/F3 cells assessed as cell growth inhibition after 72 hrs by CellTiter-Glo assay, GI50 = 0.0672 μM.	29136465
BAF3	Antiproliferative assay		72 hrs	Antiproliferative activity against mouse BAF3 cells harboring EGFR 19D/T790M/C797S mutant after 72 hrs by resazurin dye based assay, IC50 = 0.26 μM.	30429956
BAF3	Antiproliferative assay		72 hrs	Antiproliferative activity against mouse BAF3 cells harboring EGFR L858R/T790M/C797S mutant after 72 hrs by resazurin dye based assay, IC50 = 0.42 μM.	30429956
NCI-H1975	Antiproliferative assay		72 hrs	Antiproliferative activity against human NCI-H1975 cells harboring EGFR L858R/T790M mutant after 72 hrs by resazurin dye based assay, IC50 = 1.09 μM.	30429956
U937	Antiproliferative assay		72 hrs	Antiproliferative activity against human ALK-negative U937 cells assessed as reduction in cell viability measured after 72 hrs by CellTiter 96 aqueous one solution cell proliferation assay, IC50 = 3.194 μM.	27144831
KARPAS299	Antitumor assay	50 mg/kg	13 days	Antitumor activity against human KARPAS299 cells expressing NMP-ALK fusion protein xenografted in SCID/beige mouse assessed as tumor regression at 50 mg/kg, po administered once daily for 13 days, NULL = NULL μM.	27144831
Click to View More Cell Line Experimental Data

Solubility

In vitro
Batch:

Ethanol : 43 mg/mL

DMSO : 1 mg/mL (1.71 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	50%DMSO 1 50%Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.750mg/ml (1.28mM)	Taking the 1 mL working solution as an example, add 500 μL of 1.5 mg/ml clear DMSO stock solution to 500 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	3.000mg/ml (5.14mM)	Taking the 1 mL working solution as an example, add 50 μL 60 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

%

% Tween 80

% ddH₂O

% DMSO

+

%

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

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.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	584.09	Formula	C₂₉H₃₉ClN₇O₂P	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1197953-54-0	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	AP26113			Smiles	CN1CCN(CC1)C2CCN(CC2)C3=CC(=C(C=C3)NC4=NC=C(C(=N4)NC5=CC=CC=C5P(=O)(C)C)Cl)OC

Mechanism of Action

Targets/IC₅₀/Ki	ALK (Cell-free assay) 0.37 nM ROS1 (Cell-free assay) 1.9 nM FLT3 (Cell-free assay) 2.1 nM IGF1R (Cell-free assay) 24.9 nM EGFR(C797S/del19) (cell-based) 39.9 nM EGFR(del19) (Cell-free assay) 43.7 nM EGFR(C797S/T790M/del19) (cell-based) 67.2 nM EGFR(T790M/del19) (cell-based) 150.3 nM InsR (Cell-free assay) 196 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. This compound overcomes the resistance of EGFR-triple-mutant and the activity depends on ATP-competitive manner with less affection to wild-type EGFR.
In vivo	Mouse PK parameters for Brigatinib following oral dosing (10 mg/kg): C_max=448 ng/mL,t_1/2=5.8 h. And in CD rats, after dosing at 3 mg/kg i.v, CL=0.46 L/(h·kg), t_1/2=4.8 h, Vss=7.8 L/kg; Dosed at 10 mg/kg p.o, Cmax=305 ng/mL, t_max=4 h, t_1/2=3.4 h， F%=52. This compound demonstrates dose-dependent antitumor activity. It 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.
References	[1] http://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.6b00306 [2] https://www.nature.com/articles/ncomms14768

Applications

Methods	Biomarkers	Images	PMID
Western blot	pEGFR / EGFR / pAkt / Akt / pERK / ERK / pS6 / S6 pALK / ALK pROS1 / ROS1 / pSTAT3 / STAT3		28287083
Growth inhibition assay	Cell viability		25351743

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT06132867	Completed	Healthy Volunteers	Takeda	January 17 2024	Phase 1
NCT04925609	Recruiting	Anaplastic Large Cell Lymphoma ALK-Positive\|Inflammatory Myofibroblastic Tumor\|Other Solid Tumor	Princess Maxima Center for Pediatric Oncology\|Takeda	August 18 2022	Phase 1\|Phase 2
NCT04718012	Completed	Lung Cancer ROS Translocated	Centre Hospitalier Intercommunal Creteil	March 17 2021	--
NCT04634110	Terminated	Brain Metastases\|Lung Cancer	University of Colorado Denver\|National Cancer Institute (NCI)	November 17 2020	Phase 2
NCT04260009	Withdrawn	Anaplastic Lymphoma Kinase Positive (ALK +) Anaplastic Large Cell Lymphoma\|Inflammatory Myofibroblastic Tumors\|Solid Tumors	Takeda	September 1 2020	Phase 1\|Phase 2
NCT04111705	Active not recruiting	Non Small Cell Lung Cancer Metastatic	Intergroupe Francophone de Cancerologie Thoracique	August 5 2020	Phase 2

Tech Support

Handling Instructions

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Brigatinib ALK inhibitor

Chemical Structure

Molecular Weight: 584.09