拉帕替尼作用機制 - Medchemexpress - MCE中國

1、Product Data SheetLapatinibCat. No.: HY-50898CAS No.: 231277-92-2分式: CHClFNOS分量: 581.06作靶點: EGFR; Autophagy; Ferroptosis作通路: JAK/STAT Signaling; Protein Tyrosine Kinase/RTK; Autophagy; Apoptosis儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 39 mg/mL (67.12 mM)

2、* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 1.7210 mL 8.6050 mL 17.2099 mL5 mM 0.3442 mL 1.7210 mL 3.4420 mL10 mM 0.1721 mL 0.8605 mL 1.7210 mL請根據(jù)產品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復凍融造成的產品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存時，請在 6 個內使

3、，-20C 儲存時，請在 1 個內使。體內實驗請根據(jù)您的實驗動物和給藥式選擇適當?shù)娜芙獍?。以下溶解案都請先按?In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實驗結果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當保存；體內實驗的作液，建議您現(xiàn)現(xiàn)配，當天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.30 mM); Clear solution此案

4、可獲得 2.5 mg/mL (4.30 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.30 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (4.30 mM，飽和度未知) 的澄 溶液，此案不適于實驗

5、周 期在半個以上的實驗。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Lapatinib (GW572016) 分別為 10.2 和 9.8 nM。種 ErbB-2 和 EGFR 酪氨酸激酶結構域的有效抑制劑，對純化的 EGFR 和 ErbB-2 的 IC50 值IC & Target EGFR ErbB210.2 nM (IC50, Cell Free 9.8 nM (IC50, Cell Free Assay)Assay)體外研究 Lapatinib (GW2016; 0.

6、03-10 M; 6 hours; BT474 and HN5 cells) treatment inhibits receptor autophosphorylation ofEGFR and ErbB-2 in a dose-responsive manner. Phosphorylation of serine 473 of AKT was inhibited by GW2016 in adose-dependent manner1.Lapatinib (GW2016; 72 hours; HN5, A-43, BT474, N87, and CaLu-3 cells) treatmen

7、t has a selective inhibition of theproliferation of human tumor cell lines1.Lapatinib (GW2016; 1-10 M; 72 hours; HN5 cells) treatment results in induces G1 arrest1.Western Blot Analysis1Cell Line: BT474 and HN5 cellsConcentration: 0.03 M, 0.1 M, 0.3 M, 1 M, 3 M, or 10 MIncubation Time: 6 hoursResult

8、: Inhibited receptor autophosphorylation of EGFR and ErbB-2 in a dose-responsivemanner. Phosphorylation of serine 473 of AKT was also inhibited in a dose-dependentmanner.Cell Proliferation Assay1Cell Line: HN5, A-43, BT474, N87, and CaLu-3 cellsConcentration:Incubation Time: 72 hoursResult: Inhibite

9、d the growth of tumor cells overexpressing EGFR or ErbB-2.Cell Cycle Analysis1Cell Line: HN5 cellsConcentration: 1 M, or 10 MIncubation Time: 72 hoursResult: Resulted in induction of G1 arrest.體內研究Lapatinib (GW2016; 30-100 mg/kg; oral administration; twice daily; for 21 days; CD-1 nude female mice)

10、treatmentinhibits tumor xenograft growth of the HN5 cells in a dose-responsive manner at 30 and 100 mg/kg, with completePage 2 of 3 www.MedChemEinhibition of tumor growth at the higher dose1.Animal Model: CD-1 nude female mice (4-6 weeks old) with HN5 cells1Dosage: 30 mg/kg, 100 mg/kgAdministration:

11、 Oral administration; twice daily; for 21 daysResult: Inhibited tumor xenograft growth of the HN5 cells in a dose-responsive manner.戶使本產品發(fā)表的科研獻 Nature. 2017 Aug 24;548(7668):471-475. Nat Med. 2016 Jul;22(7):723-6. Nat Immunol. 2018 Mar;19(3):233-245. Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq109

12、3. Oncogene. 2016 Jun 9;35(23):2961-70.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Rusnak DW, et al. The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth ofhuman normal and tumor-derived cell lines in vitro and in vivo. Mol Cancer Ther. 2001 Dec;1(2):85-94McePdfHeightCaution: Product has not be