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Brigatinib

Name: Brigatinib
Brand: Selleck Chemicals
SKU: S8229
Rating: 5 (40 reviews)

Synonyms: AP26113

Catalog No.S8229 Purity:99.91%

Brigatinib 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 Chemical Structure

CAS No. 1197953-54-0

Purity & Quality Control

Batch: Purity: 99.91%

99.91

Brigatinib Related Products

Related Products	TAE684 (NVP-TAE684) GSK1838705A Repotrectinib (TPX-0005) AZD3463 AP26113-analog (ALK-IN-1) Ensartinib dihydrochloride ASP3026	Click to Expand
Related Compound Libraries	Tyrosine Kinase Inhibitor Library PI3K/Akt Inhibitor Library Angiogenesis Related compound Library HIF-1 Signaling Pathway Compound Library FDA-approved Anticancer Drug Library	Click to Expand

Signaling Pathway

ALK Signaling Pathway

Cell Data

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

Biological Activity

Description

Brigatinib 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)	Click to View More Targets
0.37 nM	1.9 nM	2.1 nM	24.9 nM	39.9 nM	Click to View More Targets

In vitro
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 Research	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).
Experimental Result Images	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

In Vivo
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. 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].
Animal Research	Animal Models	female CD rats
	Dosages	10 mg/kg(p.o); 2 mg/kg(i.v)
	Administration	p.o, i.v

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-05-22)
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

References

Chemical Information & Solubility

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

In vitro
Batch:

Ethanol : 43 mg/mL

DMSO : 1 mg/mL ( (1.71 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Molecular Weight Calculator

In vivo Batch: Add solvents to the product individually and in order.				In vivo Formulation Calculator
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.

Preparing Stock Solutions

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

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.

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

Tel: +1-832-582-8158 Ext:3
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