Bafetinib

製品コードS1369 バッチS136908

化学情報

	Synonyms	INNO-406, NS-187	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₃₀H₃₁F₃N₈O
	分子量	576.62	CAS No.	859212-16-1
Solubility (25°C)*	体外	DMSO	100 mg/mL (173.42 mM)
		Water	Insoluble
		Ethanol	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	Bafetinib is a potent and selective dual Bcr-Abl/Lyn inhibitor with IC50 of 5.8 nM/19 nM in cell-free assays, does not inhibit the phosphorylation of the T315I mutant and is less potent to PDGFR and c-Kit.
in vitro	Bafetinib blocks WT Bcr-Abl autophosphorylation and its downstream kinase activity with IC50 of 11 nM and 22 nM in K562 and 293T cells, respectively. Bafetinib suppresses the growth of the Bcr-Abl-positive cell lines including K562, KU812, and BaF3/wt cells potently without effects on the proliferation of the Bcr-Abl-negative U937 cell line. Moreover, Bafetinib exhibits a dose-dependent antiproliferative effect against Bcr-Abl point mutant cell lines, such as BaF3/E255K cells. ^[1] In Bcr-Abl+ leukemia cell lines, Bafetinib induces both caspase-mediated and caspase-independent cell death by blocking the phosphorylation of Bcr-Abl. ^[2]
in vivo	In Bcr-Abl–positive KU812 mouse model, Bafetinib (0.2 mg/kg/day) significantly inhibits tumor growth, and completely inhibits tumor growth without adverse effects at 20 mg/kg/day. For Balb/c mice, Bafetinib shows maximal tolerated dose of 200 mg/kg/d and bioavailability value (BA) of 32%. ^[1] In a Central nervous system (CNS) leukemia model bearing Ba/F3/wt bcr-ablGFP, Ba/F3/Q252H, or Ba/F3/M351T cells, combination treatment of Bafetinib (60 mg/kg) and cyclosporine A (CsA) (50 mg/kg) leads to more significant inhibition of leukemia growth in the brain than either Bafetinib or CsA alone. ^[3]
特徴	Dual Bcr-Abl/Lyn inhibitor.

プロトコル(参考用のみ)

キナーゼアッセイ	Kinase assay
キナーゼアッセイ	Bcr-Abl kinase assays are performed in 25 μL of reaction mixture containing 250 μM peptide substrate, 740 Bq/μL [γ-³³P]ATP, and 20 μM cold adenosine triphosphate (ATP) by using the SignaTECT protein tyrosine kinase assay system. Each Bcr-Abl kinase is used at a concentration of 10 nM. Kinase assays for Abl, Src, and Lyn are carried out with an enzyme-linked immunosorbent assay (ELISA) kit. The inhibitory effects of NS-187 against 79 tyrosine kinases are tested with KinaseProfiler.
細胞アッセイ	細胞株	K562, BaF3/wt, BaF3/E255K, and BaF3/T315I cells
	濃度	0-10 μM
	反応時間	72 hours
	実験の流れ	K562, BaF3/wt, BaF3/E255K, and BaF3/T315I cells are plated at 1 × 10³ in 96-well plates, whereas KU812 and U937 cells are plated at 5 × 10³ in 96-well plates. Cells are incubated with serial dilutions of Bafetinib for 3 days. Cell proliferation is measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; Nacalai Tesque) assay, and the 50% inhibitory concentration (IC50) values are calculated by fitting the data to a logistic curve.
動物実験	動物モデル	KU812 xenograft is established by subcutaneous injection of KU812 cells into the right flank of Balb/c-nu/nu female mice.
	投薬量	≤20 mg/kg/day
	投与方法	Administered via p.o.

参考

カスタマーフィードバック

: Data from [Data independently produced by , , Scientific Reports, 2016, 6:25694.]

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：

Focal adhesion kinase activation by calcium-dependent calpain is involved in chronic lymphocytic leukaemia cell aggressiveness [ Br J Haematol, 2023, 10.1111/bjh.18996]	PubMed: 37495265
Tyrosine Kinase Inhibitor Profiling Using Multiple Forskolin-Responsive Reporter Cells [ Int J Mol Sci, 2023, 10.3390/ijms241813863]	PubMed: 37762164
Tyrosine Kinase Inhibitor Profiling Using Multiple Forskolin-Responsive Reporter Cells [ Int J Mol Sci, 2023, 24(18)13863]	PubMed: 37762164
Lyn-mediated glycolysis enhancement of microglia contributes to neuropathic pain through facilitating IRF5 nuclear translocation in spinal dorsal horn [ J Cell Mol Med, 2023, 10.1111/jcmm.17759]	PubMed: 37132040
A community challenge for a pancancer drug mechanism of action inference from perturbational profile data [ Cell Rep Med, 2022, 3(1):100492]	PubMed: 35106508
Listeria toxin promotes phosphorylation of the inflammasome adaptor ASC through Lyn and Syk to exacerbate pathogen expansion [ Cell Rep, 2022, 38(8):110414]	PubMed: 35196496
Establishment and Characterization of NCC-PMP1-C1: A Novel Patient-Derived Cell Line of Metastatic Pseudomyxoma Peritonei [ J Pers Med, 2022, 12(2)258]	PubMed: 35207746
Brain-Derived Neurotrophic Factor regulates LYN kinase mediated Myosin Light Chain Kinase activation to modulate non-muscle myosin II activity in hippocampal neurons [ J Biol Chem, 2022, S0021-9258(22)00494-X]	PubMed: 35598826
Establishment and characterization of NCC-UPS4-C1: a novel cell line of undifferentiated pleomorphic sarcoma from a patient with Li-Fraumeni syndrome [ Hum Cell, 2022, 10.1007/s13577-022-00671-y]	PubMed: 35118583
A hotspot mutation in transcription factor IKZF3 drives B cell neoplasia via transcriptional dysregulation [ Cancer Cell, 2021, 39(3):380-393.e8]	PubMed: 33689703

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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