Afatinib

製品コードS1011 バッチS101111

化学情報

	Synonyms	BIBW2992	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₄H₂₅ClFN₅O₃
	分子量	485.94	CAS No.	850140-72-6
Solubility (25°C)*	体外	DMSO	97 mg/mL (199.61 mM)
		Ethanol	97 mg/mL (199.61 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	アファチニブ (Afatinib) は in vitro において EGFR/ErbB を不可逆的に阻害します。IC50 は EGFR^wt, EGFR^L858R, EGFR^L858R/T790M ErbB2 (HER2) and ErbB4 (HER4) に対してそれぞれ 0.5, 0.4, 10, 14 および 1 nM です。アファチニブによってオートファジー (autophagy) が誘発されることが報告されています。
in vitro	BIBW2992 shows potent activity against both wild-type and mutant forms of EGFR and HER2. It is similar to Gefitinib in potency against L858R EGFR, but about 100-fold more active against the Gefitinib resistant L858R-T790M EGFR double mutant. BIBW2992 exhibits potent effects on both EGFR and HER2 phosphorylation in vivo. It compares favorably to reference compounds (such as Lapatinib et al.) in all cell types tested, such as human epidermoid carcinoma cell line A431 expressing wt EGFR, murine NIH-3T3 cells transfected with wt HER2, as well as breast cancer cell line BT-474 and gastric cancer cell line NCI-N87, which express endogenous HER2. ^[1]
in vivo	Daily oral administration of BIBW2992 at 20 mg/kg for 25 days results in dramatic tumor regression with a cumulative treated/control tumor volume ratio (T/C ratio) of 2%. Reduced phosphorylation of EGFR and AKT is confirmed by immunohistochemical staining of tissue sections. Therefore, like lapatinib and neratinib, BIBW2992 is a next generation tyrosine kinase inhibitor (TKI) that inhibits human epidermal growth factor receptor 2 (Her2) and epidermal growth factor receptor (EGFR) kinases irreversibly. BIBW2992 is not only active against EGFR mutations targeted by first generation TKIs like Erlotinib or Gefitinib, but also against those insensitive to these standard therapies. ^[1]

プロトコル(参考用のみ)

キナーゼアッセイ	In vitro kinase activity assays
キナーゼアッセイ	The wild type tyrosine kinase domain of the human EGFR as well as that of the EGFR L858R/T790M double mutant are fused to Glutathione-S-transferase (GST), and extracted. Enzyme activity is then assayed in the presence of the inhibitor BIBW2992, serially diluted in 50% DMSO. A random polymer pEY (4:1) is used as substrate and biotinylated pEY (bio-pEY) is added as a tracer substrate. The kinase domain of HER2 is cloned using the baculovirus system and extracted similarly to that of EGFR kinase. Details of assays for EGFR, HER2, SRC, BIRK and VEGFR2 kinase activity are available in Supplementary information.
細胞アッセイ	細胞株	NSCLC cells
	濃度	0-10 μM
	反応時間	1 hour
	実験の流れ	1 × 10⁴ NSCLC cells are transferred into each well of a 96-well plate and cultured overnight in serum-free media for the EGFR phosphorylation assay. After addition of BIBW2992 on the next day, the plates are incubated at 37 °C for 1 hour. EGF-stimulation is done using 100 ng/mL for 10 min at room temperature. Cells are washed with ice cold PBS, extracted with 120 μL HEPEX buffer per well and shaken at room temperature for 1 hour. In all 2 × 10⁴ cells per well is used for the HER2 phosphorylation assay. Streptavidin precoated plates are coated with anti-EGFR-biotin at 1:100 dilution in blocking buffer and c-erb2/HER2 oncoprotein Ab-5(Clone N24)-Biotin. Cell extracts is then transferred to the antibody-coated wells and incubated at room temperature for 1 hour. Extinction is measured at 450 nm.
動物実験	動物モデル	Athymic NMRI-nu/nu female mice
	投薬量	20 mg/kg
	投与方法	Oral administration

参考

カスタマーフィードバック

: Data from [Int J Proteomics, 2011, 2011, 215496]

: Data from [Int J Proteomics, 2011, 2011, 215496]

: , , Dr. Zhang of Tianjin Medical University

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：

Human fetal brain self-organizes into long-term expanding organoids [ Cell, 2024, 187(3):712-732.e38]	PubMed: 38194967
Tubuloid differentiation to model the human distal nephron and collecting duct in health and disease [ Cell Rep, 2024, 43(1):113614]	PubMed: 38159278
A destabilizing Y891D mutation in activated EGFR impairs sensitivity to kinase inhibition [ NPJ Precis Oncol, 2024, 8(1):3]	PubMed: 38182677
Romidepsin and afatinib abrogate JAK-STAT signaling and elicit synergistic antitumor effects in cutaneous T-cell lymphoma [ J Invest Dermatol, 2024, S0022-202X(23)03210-4]	PubMed: 38219917
The Diagnostic Value of ACSL1, ACSL4, and ACSL5 and the Clinical Potential of an ACSL Inhibitor in Non-Small-Cell Lung Cancer [ Cancers (Basel), 2024, 16(6)1170]	PubMed: 38539505
Non-small cell lung cancer cells with uncommon EGFR exon 19delins variants respond poorly to third-generation EGFR inhibitors [ Transl Oncol, 2024, 39:101834]	PubMed: 38006760
Antitumor activity of afatinib in EGFR T790M-negative human oral cancer therapeutically targets mTOR/Mcl-1 signaling axis [ Research Square, 2024, 10.21203/rs.3.rs-3872267/v1]	PubMed: none
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
Cellular mechanisms of heterogeneity in NF2-mutant schwannoma [ Nat Commun, 2023, 14(1):1559]	PubMed: 36944680
Phase 1b trial of anti-EGFR antibody JMT101 and Osimertinib in EGFR exon 20 insertion-positive non-small-cell lung cancer [ Nat Commun, 2023, 14(1):3468]	PubMed: 37308490

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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