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Synonyms | GSK572016, GW2016 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C29H26ClFN4O4S |
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分子量 | 581.06 | CAS No. | 231277-92-2 | |
Solubility (25°C)* | 体外 | DMSO | 100 mg/mL (172.09 mM) | |
Water | Insoluble | |||
Ethanol | 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. |
製品説明 | Lapatinib, used in the form of Lapatinib Ditosylate, is a potent EGFR and ErbB2 inhibitor with IC50 of 10.8 and 9.2 nM in cell-free assays, respectively. Lapatinib induces ferroptosis and autophagic cell death. |
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in vitro | Lapatinib 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 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 inhibits the growth of both EGFR- and ErbB2-overexpressing cells. Lapatinib 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 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 (~100 mg/kg) twice daily significantly inhibits the growth of BT474 and HN5 xenografts in a dose-dependent manner. [1] |
キナーゼアッセイ | In vitro kinase assays | |
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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 cells |
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 |
Data from [Cancer Lett, 2013, 340(1), 43-50]
Data from [Mol Oncol, 2013, 7(3), 392-401]
Data from [Mol Carcinog, 2013, 52(12), 959-69]
Tumor-acquired somatic mutation affects conformation to abolish ABCG2-mediated drug resistance [ Drug Resist Updat, 2024, 73:101066] | PubMed: 38387283 |
The net electrostatic potential and hydration of ABCG2 affect substrate transport [ Nat Commun, 2023, 14(1):5035] | PubMed: 37596258 |
Single cell profiling of female breast fibroadenoma reveals distinct epithelial cell compositions and therapeutic targets [ Nat Commun, 2023, 10.1038/s41467-023-39059-3] | PubMed: 37328469 |
Single cell profiling of female breast fibroadenoma reveals distinct epithelial cell compositions and therapeutic targets [ Nat Commun, 2023, 14(1):3469] | PubMed: 37328469 |
The net electrostatic potential and hydration of ABCG2 affect substrate transport [ Nat Commun, 2023, 14(1):5035] | PubMed: 37596258 |
Inhibiting the glycerophosphodiesterase EDI3 in ER-HER2+ breast cancer cells resistant to HER2-targeted therapy reduces viability and tumour growth [ J Exp Clin Cancer Res, 2023, 42(1):25] | PubMed: 36670508 |
New hormone receptor-positive breast cancer mouse cell line mimicking the immune microenvironment of anti-PD-1 resistant mammary carcinoma [ J Immunother Cancer, 2023, 11(6)e007117] | PubMed: 37344100 |
Irreversible HER2 inhibitors overcome resistance to the RSL3 ferroptosis inducer in non-HER2 amplified luminal breast cancer [ Cell Death Dis, 2023, 14(8):532] | PubMed: 37596261 |
FGFR blockade inhibits targeted therapy-tolerant persister in basal FGFR1- and FGF2-high cancers with driver oncogenes [ NPJ Precis Oncol, 2023, 7(1):107] | PubMed: 37880373 |
FGFR blockade inhibits targeted therapy-tolerant persister in basal FGFR1- and FGF2-high cancers with driver oncogenes [ NPJ Precis Oncol, 2023, 7(1):107] | PubMed: 37880373 |
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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