Lapatinib Ditosylate

製品コードS1028 バッチS102812

印刷

化学情報

Chemical Structure 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
分子量 925.46 CAS No. 388082-77-7
Solubility (25°C)* 体外 DMSO 100 mg/mL (108.05 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
2%DMSO 40%PEG300 5%Tween80 53%ddH2O
1.25mg/ml Taking the 1 mL working solution as an example, add 20 μL 62.5 mg/ml clear DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 530 μL ddH2O to make it clear. Volume up to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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 Lapatinib Ditosylate is a potent EGFR and ErbB2 inhibitor with IC50 of 10.8 and 9.2 nM in cell-free assays, respectively.
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

Data from [Mol Cancer Ther, 2011, 10:697-707]

Data from [Biochem Pharmacol, 2011, 82, 1457-1466]

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：

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
Irreversible tyrosine kinase inhibitors induce the endocytosis and downregulation of ErbB2 [ Biochem Biophys Rep, 2023, 34:101436] PubMed: 36824069
Proteo-genomic characterization of virus-associated liver cancers reveals potential subtypes and therapeutic targets [ Nat Commun, 2022, 13(1):6481] PubMed: 36309506
Organoid screening reveals epigenetic vulnerabilities in human colorectal cancer [ Nat Chem Biol, 2022, 10.1038/s41589-022-00984-x] PubMed: 35273398
Sustained oncogenic signaling in the cytostatic state enables targeting of non-proliferating persistent cancer cells [ Cancer Res, 2022, can.21.2908] PubMed: 35792658
Regulatory chromatin rewiring promotes metabolic switching during adaptation to oncogenic receptor tyrosine kinase inhibition [ Oncogene, 2022, 41(43):4808-4822] PubMed: 36153371

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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