Afatinib (BIBW2992)

貨號 Cat. No.: A8247-10mg
規格 Size: 10mg
品牌 Brand: APExBIO

Description

Biological Activity

Description	Afatinib (BIBW2992) is an irreversible inhibitor of EGFR/HER2 for EGFR(wt), EGFR(L858R), EGFR(L858R/T790M) and HER2 with IC50 of 0.5 nM, 0.4 nM, 10 nM and 14 nM, respectively; 100-fold more active against Gefitinib-resistant L858R-T790M EGFR mutant.
Targets	EGFR^wt	EGFR^L858R	EGFR^L858R/T790M	HER2
IC50	0.5 nM	0.4 nM	10 nM	14 nM

Protocol

Cell experiment: [1]
Cell lines	NCI-H1975 and BT474 cells
Preparation method	The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.
Reaction Conditions	EC50: 92 nM for NCI-H1975 cells, 54 nM for BT474 cells; 96 hours
Applications	The effect of the inhibitor on cellular proliferation was tested in various assay formats including anchorage-dependent (BT474 cells grown on plastic; two-dimensional assays) and anchorage-independent (NCI-H1975 cells grown in soft agar; three-dimensional assays) assays. Afatinib dose-dependently inhibited cell proliferation and showed nanomolar activity. The EC50 values for NCI-H1975 and BT474 cells were 92 nM and 54 nM, respectively.
Animal experiment: [2]
Animal models	Transgenic mice expressing the delE748-A752 version of mouse Egfr and the L858R version of human EGFR
Dosage form	Oral administration, 5 mg/kg, once daily, 5 days per week
Applications	The transgenic mice received the oral administration of the drug until toxicity or death. All mice in the control group died, with a median survival time of 119 days. Afatinib treatment significantly enhanced the survival of transgenic mice with a median survival time of 456 days. No toxic death was observed in any mice. Four weeks after the initiation of treatment, body weight in the control group was significantly lower than in the afatinib group.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1] Solca F, Dahl G, Zoephel A, et al. Target binding properties and cellular activity of afatinib (BIBW 2992), an irreversible ErbB family blocker. Journal of Pharmacology and Experimental Therapeutics, 2012, 343(2): 342-350. [2] Ninomiya T, Takigawa N, Ichihara E, et al. Afatinib prolongs survival compared with gefitinib in an epidermal growth factor receptor-driven lung cancer model. Molecular cancer therapeutics, 2013, 12(5): 589-597.

Chemical Properties

Cas No.	439081-18-2
Chemical Name	(E)-N-[4-(3-chloro-4-fluoroanilino)-7-[(3S)-oxolan-3-yl]oxyquinazolin-6-yl]-4-(dimethylamino)but-2-enamide
Canonical SMILES	CN(C)CC=CC(=O)NC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)OC4CCOC4
Formula	C₂₄H₂₅ClFN₅O₃	M.Wt	485.94
Solubility	>24.3mg/mL in DMSO	Storage	Store at -20°C
General tips	For obtaining a higher solubility , please warm the tube at 37 â„ƒ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20â„ƒ for several months.
Shipping Condition	Evaluation sample solution : ship with blue ice All other available size: ship with RT , or blue ice upon request