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受注：045-509-1970 |
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化学情報
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Synonyms | BIBW2992 Dimaleate | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C24H25ClFN5O3.2C4H4O4 |
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| 分子量 | 717.18 | CAS No. | 850140-73-7 | |
| Solubility (25°C)* | 体外 | DMSO | 100 mg/mL (139.43 mM) | |
| Water | Insoluble | |||
| Ethanol | Insoluble | |||
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* <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. |
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溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | Afatinib Dimaleate irreversibly inhibits EGFR/HER2 including 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. Afatinib (BIBW2992) Dimaleate induces autophagy. |
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| in vitro | BIBW2992 is more effective than erlotinib, gefitinib, or lapatinib in inhibiting survival of lung cancer cell lines harboring wild-type (H1666) or L858R/T790M (NCI-H1975) EGFR. BIBW2992 is similarly effective against NSCLC lines expressing HER2 776insV (NCI-H1781) or EGFR E746_A750del (HCC827), but shows no activity toward A549 cells, which express wild-type EGFR and HER2.[1] Afatinib enhances cytotoxicity of topotecan and mitoxantrone to SP cells, and increases the apoptosis induced by topotecan and mitoxantrone in SP cells.[2] |
| in vivo | In the MDA-MB-453 xenograft model, BIBW2992 (20 mg/kg, p.o.) results in dramatic tumor regression with a cumulative treated/control tumor volume ratio (T/C ratio) of 2%, and downregulation of EGFR and AKT phosphorylation.[1] In A7, A431, FaDu, UT-SCC-14 and UT-SCC-15 xenograft models, application of BIBW 2992 (30 mg/kg, p.o.) leads to a significant prolongation of tumour growth time.[3] In HER2-amplified xenograft medel, Afatinib (30 mg/kg, p.o.) results a markedly inhibition in tumor growth and a significant improvement in the duration of overall survival.[4] In HER2-positive gastric cancer NCI-N87 xenograft, afatinib (25 mg/kg, p.o.) leads to dramatic tumor volume regression within 4 d and near-complete tumor resolution after 21 d of treatment.[5] |
プロトコル(参考用のみ)
| キナーゼアッセイ | In vitro kinase activity assay | |
|---|---|---|
| EGFR kinase: Each 100 µL enzyme reaction contained 10 μL of inhibitor in 50% Me2SO, 20 μL of substrate solution (200 mM HEPES pH 7.4, 50 mM Mg-acetate, 2.5 mg/mL poly (EY), 5 μg/mL bio-pEY) and 20 µL enzyme preparation. The enzymatic reaction is started by addition of 50 µL of a 100 µM ATP solution made in 10 mM MgCl2. Assays are carried out at room temperature for 30 min and terminated by the addition of 50 µL of stop solution (250 mM EDTA in 20 mM HEPES pH 7.4). 100 µL are transferred to a streptavidin coated microtiterplate, after an incubation time of 60 min at room temperature the plate is washed with 200 µL of wash solution (50 mM Tris, 0.05% Tween20). A 100 µL aliquot of a HRPO- labeled anti-PY antibody (PY20H Anti-Ptyr:HRP ) 250 ng/mL are added to the wells. After 60 min of incubation, the plate is washed three times with a 200 µL wash solution. The samples are then developed with a 100µL TMB Peroxidase Solution (A:B= 1:1). The reaction is stopped after 10 min. The plate is transferred to an ELISA reader and extinction is measured at OD450nm. HER2-IC enzyme: Enzyme activity is assayed in the presence or absence of serial inhibitor dilutions performed in 50 % Me2SO. Each 100 µL reaction contains similar components as described for EGFR kinase assay with addition of 1000 µM Na3VO4. The enzymatic reaction is started by addition of 50µL of 500 µM ATP solution made in 10 mM Mg-acetate. The dilution of the enzyme is set so that incorporation of phosphate into bio-pEY is linear with respect to time and amount of enzyme. The enzyme preparation is diluted in 20 mM HEPES pH 7.4, 130 mM NaCl, 0.05% Triton X-100, 1 mM DTT and 10% glycerol. Assays are carried out at room temperature for 30 min and terminated by the addition of 50 µL of stop solution. Src kinase assays: Each 100 µL reaction contained 10 µL of inhibitor in 50 % Me2SO, 20µL of enzyme preparation, 20 µL of substrate solution supplemented with 1000 µM Na3VO4. The enzymatic reaction is started by addition of 50 µL of a 1000 µM ATP solution made in 10 mM Mg-acetate. BIRK kinase assay: 250 mM Tris pH 7.4, 10mM DTT, 2.5 mg/mL poly(EY), 5 mg/mL bio-pEY is used as substrate solution and enzymatic reaction is started by addition of 50 µL of a 2 mM ATP solution made in 8 mM MnCl2, 20 mM Mg-acetate. VEGF2 and HGFR kinase assays: Assays are carried out at room temperature for 20 minutes and terminated by the addition of 10 µL of 5 % H3PO4. The precipitate is then trapped onto GF/B filters using a 96 well filter mate universal harvester. After extensive washing the filter plate is dried for 1 h at 50°C, sealed and incorporated radioactivity is determined by scintillation counting using a TopCount™ or a Microbeta b counter™. | ||
| 細胞アッセイ | 細胞株 | SP and NSP cell lines |
| 濃度 | 1 μM | |
| 反応時間 | 48 h | |
| 実験の流れ | Cytotoxicity is determined using MTT assay. The IC 50 value is defined as the drug concentration resulting in 50% cell death. Both the fitted sigmoidal dose response curve and IC50 are calculated by Bliss method. | |
| 動物実験 | 動物モデル | SCID mice harbouring ARK2 xenografts |
| 投薬量 | 25 mg/kg | |
| 投与方法 | p.o. | |
参考
カスタマーフィードバック
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Data from [Data independently produced by Int J Proteomics, 2011, 215496]
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Data from [Data independently produced by Int J Proteomics, 2011, 215496]
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Data from [Data independently produced by , , Cancer Discov, 2017, 7(6):575-585]
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：
| 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 |
| Discovery of nontriterpenoids from the rot roots of Panax notoginseng with cytotoxicity and their molecular docking study and experimental validation [ RSC Adv, 2023, 13(16):11037-11043] | PubMed: 37033442 |
| Irreversible tyrosine kinase inhibitors induce the endocytosis and downregulation of ErbB2 [ Biochem Biophys Rep, 2023, 34:101436] | PubMed: 36824069 |
| Silent mutations reveal therapeutic vulnerability in RAS Q61 cancers [ Nature, 2022, 603(7900):335-342] | PubMed: 35236983 |
| Group 3 innate lymphoid cells produce the growth factor HB-EGF to protect the intestine from TNF-mediated inflammation [ Nat Immunol, 2022, 23(2):251-261] | PubMed: 35102343 |
| PI3Kγ stimulates a high molecular weight form of myosin light chain kinase to promote myeloid cell adhesion and tumor inflammation [ Nat Commun, 2022, 13(1):1714] | PubMed: 35361816 |
| Pyruvate Facilitates FACT-Mediated γH2AX Loading to Chromatin and Promotes the Radiation Resistance of Glioblastoma [ Adv Sci (Weinh), 2022, 10.1002/advs.202104055] | PubMed: 35048565 |
| EGFR/MET promotes hepatocellular carcinoma metastasis by stabilizing tumor cells and resisting to RTKs inhibitors in circulating tumor microemboli [ Cell Death Dis, 2022, 13(4):351] | PubMed: 35428350 |
| Aurora kinase blockade drives de novo addiction of cervical squamous cell carcinoma to druggable EGFR signalling [ Oncogene, 2022, 10.1038/s41388-022-02256-3] | PubMed: 35250028 |
| HER3 activation contributes toward the emergence of ALK inhibitor-tolerant cells in ALK-rearranged lung cancer with mesenchymal features [ NPJ Precis Oncol, 2022, 6(1):5] | PubMed: 35042943 |
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。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。