Brigatinib

製品コードS8229 バッチS822903

化学情報

	Synonyms	AP26113	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₉H₃₉ClN₇O₂P
	分子量	584.09	CAS No.	1197953-54-0
Solubility (25°C)*	体外	DMSO	3 mg/mL warmed with 50ºC water bath (5.13 mM)
		Ethanol	2 mg/mL warmed with 50ºC water bath (3.42 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	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.
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].
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].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	U937 cells, Karpas-299 cells, H3122 cells
	濃度	--
	反応時間	72 h
	実験の流れ	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).
動物実験	動物モデル	female CD rats
	投薬量	10 mg/kg(p.o); 2 mg/kg(i.v)
	投与方法	p.o, i.v

参考

カスタマーフィードバック

: Data from [Data independently produced by , , Mol Cancer Res, 2017, 15(1):106-114]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Secondary Mutations of the EGFR Gene That Confer Resistance to Mobocertinib in EGFR Exon 20 Insertion [ J Thorac Oncol, 2023, S1556-0864(23)00797-9]	PubMed: 37666482
Adaptive resistance to lorlatinib via EGFR signaling in ALK-rearranged lung cancer [ NPJ Precis Oncol, 2023, 7(1):12]	PubMed: 36702855
Synthesis and Preclinical Evaluation of [Methylpiperazine-11C]brigatinib as a PET Tracer Targeting Both Mutated Epidermal Growth Factor Receptor and Anaplastic Lymphoma Kinase [ J Med Chem, 2023, 66(17):12130-12140]	PubMed: 37647220
Synthesis and Preclinical Evaluation of [Methylpiperazine-11C]brigatinib as a PET Tracer Targeting Both Mutated Epidermal Growth Factor Receptor and Anaplastic Lymphoma Kinase [ J Med Chem, 2023, 10.1021/acs.jmedchem.3c00722]	PubMed: 37647220
Tyrosine Kinase Inhibitors Target B Lymphocytes [ Biomolecules, 2023, 13(3)438]	PubMed: 36979373
Development of the nonreceptor tyrosine kinase FER-targeting PROTACs as a potential strategy for antagonizing ovarian cancer cell motility and invasiveness [ J Biol Chem, 2023, 299(6):104825]	PubMed: 37196766
Discovery of HCD3514 as a potent EGFR inhibitor against C797S mutation in vitro and in vivo [ J Cancer, 2023, 14(1):152-162]	PubMed: 36605493
Selective Impact of ALK and MELK Inhibition on ERα Stability and Cell Proliferation in Cell Lines Representing Distinct Molecular Phenotypes of Breast Cancer [ bioRxiv, 2023, 10.1101/2023.12.19.572304]	PubMed: none
An in vivo model of glioblastoma radiation resistance identifies long non-coding RNAs and targetable kinases [ JCI Insight, 2022, e148717]	PubMed: 35852875
STAT3 inhibition suppresses adaptive survival of ALK-rearranged lung cancer cells through transcriptional modulation of apoptosis [ NPJ Precis Oncol, 2022, 6(1):11]	PubMed: 35228642

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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