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受注：045-509-1970 |
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化学情報
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Synonyms | GW-572016 Ditosylate | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C29H26ClFN4O4S.2C7H8O3S |
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| 分子量 | 925.46 | CAS No. | 388082-77-7 | |
| Solubility (25°C)* | 体外 | DMSO | 185 mg/mL (199.9 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 | Lapatinib Ditosylate is a potent EGFR and ErbB2 inhibitor with IC50 of 10.8 and 9.2 nM in cell-free assays, respectively. |
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| in vitro | Lapatinib Ditosylate weakly inhibits the activity of ErbB4 with IC50 of 367 nM, and displays >300-fold selectivity for EGFR and ErbB2 over other kinases such as c-Src, c-Raf, MEK, ERK, c-Fms, CDK1, CDK2, p38, Tie-2, and VEGFR2. Lapatinib Ditosylate significantly inhibits receptor autophosphorylation of EGFR and ErbB2 in a dose-dependent manner with IC50 of 170 nM and 80 nM, respectively in HN5 cells; as well as 210 nM and 60 nM, respectively in BT474 cells. Unlike OSI-774 and Iressa (ZD1839) which preferentially inhibit the growth of the EGFR-overexpressing cells, Lapatinib Ditosylate inhibits the growth of both EGFR- and ErbB2-overexpressing cells. Lapatinib Ditosylate displays higher inhibitory activity against EGFR- or ErbB2-overexpressing cells with IC50 of 0.09-0.21 μM, compared with cells expressing low levels of EGFR or ErbB2 with IC50 of 3-12 μM, and exhibits ~100-fold selectivity over the normal fibroblast cells. Lapatinib Ditosylate potently inhibits the outgrowth of EGFR-overexpressing HN5 and A-431 cells, as well as ErbB2-overexpressing BT474 and N87 cells, and significantly induces G1 arrest of HN5 cells and apoptosis of BT474 cells, which are associated with inhibition of AKT phosphorylation. [1] |
| in vivo | Oral administration of Lapatinib Ditosylate (~100 mg/kg) twice daily significantly inhibits the growth of BT474 and HN5 xenografts in a dose-dependent manner. [1] |
プロトコル(参考用のみ)
| キナーゼアッセイ | In vitro kinase assays | |
|---|---|---|
| The IC50 values for inhibition of enzyme activity are generated by measuring inhibition of phosphorylation of a peptide substrate. The intracellular kinase domains of EGFR and ErbB2 are purified from a baculovirus expression system. EGFR and ErbB2 reactions are performed in 96-well polystyrene round-bottomed plates in a final volume of 45 μL. Reaction mixtures contain 50 mM 4-morpholinepropanesulfonic acid (pH 7.5), 2 mM MnCl2, 10 μM ATP, 1 μCi of [γ33P] ATP/reaction, 50 μM Peptide A [Biotin-(amino hexonoic acid)-EEEEYFELVAKKK-CONH2], 1 mM dithiothreitol, and 1 μL of DMSO containing serial dilutions of Lapatinib beginning at 10 μM. The reaction is initiated by adding the indicated purified type-1 receptor intracellular domain. The amount of enzyme added is 1 pmol/reaction (20 nM). Reactions are terminated after 10 minutes at 23°C by adding 45 μL of 0.5% phosphoric acid in water. The terminated reaction mix (75 μL) is transferred to phosphocellulose filter plates. The plates are filtered and washed three times with 200 μL of 0.5% phosphoric acid. Scintillation cocktail (50 μL) is added to each well, and the assay is quantified by counting in a Packard Topcount. IC50 values are generated from 10-point dose-response curves. | ||
| 細胞アッセイ | 細胞株 | HFF, MCF-7, T47D, A-431, HN5, BT474, N87, CaLu-3, HB4a, and HB4a c5.2 |
| 濃度 | Dissolved in DMSO, final concentrations ~100 μM | |
| 反応時間 | 72 hours | |
| 実験の流れ | Cells are exposed to various concentrations of Lapatinib for 72 hours. Relative cell number is estimated using methylene blue staining. The absorbance at 620 nm is read in a Spectra microplate reader. Cell death and cell cycle analysis are assessed by propidium iodide staining and antibody detection of incorporated BrdUrd and staining with propidium iodide. | |
| 動物実験 | 動物モデル | CD-1 nude female mice implanted s.c. with HN5 cells, and C.B-17 SCID female mice implanted s.c. with BT474 cells |
| 投薬量 | ~100 mg/kg | |
| 投与方法 | Orally twice daily | |
カスタマーフィードバック
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Data from [Mol Cancer Ther, 2011, 10:697-707]
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Data from [Biochem Pharmacol, 2011, 82, 1457-1466]
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Data from [Biochem Pharmacol, 2011, 82, 1457-1466]
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：
| Altered ribosomal profile in acquired resistance and reversal associates with pathological response to chemotherapy in inflammatory breast cancer [ NPJ Breast Cancer, 2024, 10(1):65] | PubMed: 39075068 |
| Profiling of ERBB receptors and downstream pathways reveals selectivity and hidden properties of ERBB4 antagonists [ iScience, 2024, 27(2):108839] | PubMed: 38303712 |
| Protocol for identifying properties of ERBB receptor antagonists using the barcoded ERBBprofiler assay [ STAR Protoc, 2024, 5(2):102987] | PubMed: 38635397 |
| Proteomic Assessment of SKBR3/HER2+ Breast Cancer Cellular Response to Lapatinib and Investigational Ipatasertib Kinase Inhibitors [ bioRxiv, 2024, 2024.04.02.587656] | PubMed: 38617302 |
| Overcoming brain-derived therapeutic resistance in HER2+ breast cancer brain metastasis [ bioRxiv, 2024, 2024.02.19.581073] | PubMed: 38529509 |
| Analysis and modeling of cancer drug responses using cell cycle phase-specific rate effects [ Nat Commun, 2023, 14(1):3450] | PubMed: 37301933 |
| HDAC Inhibition Restores Response to HER2-Targeted Therapy in Breast Cancer via PHLDA1 Induction [ Int J Mol Sci, 2023, 24(7)6228] | PubMed: 37047202 |
| Integrin αvβ3 Is a Master Regulator of Resistance to TKI-Induced Ferroptosis in HER2-Positive Breast Cancer [ Cancers (Basel), 2023, 15(4)1216] | PubMed: 36831558 |
| Oncogenic ERRB2 signals through the AP-1 transcription factor to control mesenchymal-like properties of oesophageal adenocarcinoma [ NAR Cancer, 2023, 5(1):zcad001] | PubMed: 36694726 |
| Genetic Deletion of the LINC00520 Homolog in Mouse Aggravates Angiotensin II-Induced Hypertension [ Noncoding RNA, 2023, 9(3)31] | PubMed: 37218991 |
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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