Lapatinib-GW572016-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemELapatinibCat. No.: HY-50898CAS No.: 231277-92-2Synonyms: GW572016分式: CHClFNOS分量: 581.06作靶点: EGFR; Autophagy作通路: JAK/STAT Signaling; Protein Tyrosine Kinase/RTK; Autophagy储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months

2、-20C 1 month溶解性数据体外实验 DMSO : 39 mg/mL (67.12 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液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请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验 Lapatinib is

3、dissolved in 0.5% methylcellulose/0.2% Tween 805. Lapatinib is dissolved in 0.5% hydroxypropylmethylcellulose (HPMC) with 0.1% Tween804.BIOLOGICAL ACTIVITY物活性 Lapatinib (GW572016)是有效的 EGFR 和 ErbB2 抑制剂，IC50 分别为10.2 和 9.8 nM。1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEIC50 & Target EGFR ErbB210.2

4、 nM (IC50, Cell Free Assay) 9.8 nM (IC50, Cell Free Assay)体外研究 The IC50 of Lapatinib (GW2016) values for inhibition of enzyme activity are generated by measuringinhibition of phosphorylation of a peptide substrate. With the exception of ErbB-4 (IC50, 367 nM), Lapatinib is300-fold selective for EGFR

5、and ErbB-2 over other kinases tested 1. IC50 values of Lapatinib (GW2016)for BT474, SKBR3, EFM192A, HCC1954, MDAMB453 and MDAMB231 cells is 3615.1 nM, 8017.3 nM,19366.5 nM, 416.6180 nM, 6.080.825 M and 7.460.102 M, respectively. Treatment with Lapatinibresults in IC50 values of 0.16 M on the EGFR- a

6、nd the ErbB-2-overexpressing tumor cell lines 2.体内研究 Lapatinib (GW2016) is potent at inhibiting the growth of BT474 and HN5 human tumor xenografts. A dose-responsive inhibition of both models occurred on treatment of tumor-bearing mice with 30 and 100 mg/kgLapatinib orally, twice daily. Complete inh

7、ibition of tumor growth is seen at the 100 mg/kg dose. At this dose,there is 1. Lapatinib (100 mg/kg/day, oral gavage) induces severe oxidative damage in the cardiac tissue ofrat 3.PROTOCOLKinase Assay 1 The intracellular kinase domains of EGFR, ErbB-2, and ErbB4 are purified from a baculovirus expr

8、essionsystem. EGFR, ErbB-2, and ErbB-4 reactions are performed in 96-well polystyrene round-bottomed plates ina final volume of 45 L. Reaction mixtures contain 50 mM 4-morpholinepropanesulfonic acid (pH 7.5), 2 mMMnCl2, 10 M ATP, 1 Ci of -33P ATP/reaction, 50 M Peptide A Biotin-(amino hexonoic acid)

9、-EEEEYFELVAKKK-CONH2, 1 mM dithiothreitol, and 1 L of DMSO containing serial dilutions of Lapatinibbeginning at 10 M. The reaction is initiated by adding the indicated purified type-1 receptor intracellulardomain. The amount of enzyme added is 1 pmol/reaction (20 nM). Reactions are terminated after

10、10 min at23C by adding 45 L of 0.5% phosphoric acid in water. The terminated reaction mix (75 L) is transferred tophosphocellulose filter plates. The plates are filtered and washed three times with 200 L of 0.5% phosphoricacid. Scintillation cocktail (50 L) is added to each well, and the assay is qu

11、antified by counting in a PackardTopcount 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 Cells are plated in 96-well plates, in the media, at the following densities: HFF and HN5, 1000 cells/well andBT474, 5000 cells/well. After 24 h, th

12、e cells are exposed to vehicle (0.3% DMSO) or Lapatinib (1 nM, 10 nM,100 nM, 1M, 10M, and 100M). Lapatinib is removed from the cells after 72 h and is replaced by eitherDMEM containing 10% FBS and 50 g/mL Gentamicin (HFF and HN5) or RPMI containing 10% FBS and 50g/mL Gentamicin (BT474). Methylene bl

13、ue staining is performed at the time points over a total period of 16days 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 13 CD-1 nude female mice are used for HN5 human tumor xenografts, which are initiated by injection of

14、 a cellsuspension in PBS:Matrigel (1:1). C.B-17 SCID female mice are used for BT474 human tumor xenografts,which are initiated by implantation of tumor fragments (20-100 mg) from established tumors. Tumor cells and2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEfragments are implanted by s.c. injec

15、tion in the right flank. The s.c. tumors are measured with calipers, andmice are weighed twice weekly. Tumor weight is estimated from tumor volume using this formula:lengthwidth2/2=tumor volume (mm3). Treatment begins when tumors are palpable, 3-5 mm in diameter.Lapatinib (30 and 100 mg/kg) is admin

16、istered p.o. twice daily for 21 days in a vehicle of sulfo-butyl-ether-cyclodextrin 10% aqueous solution (CD10).Rats 3Wistar rats (12-week-old albino males) are randomly assigned to three groups: control (C, n=8), Trastuzumab(T, n=8) and Lapatinib (L, n=8) treatments. The control animals are untreat

17、ed, but the others in groups T andLapatinib are administered with the chemotherapy drugs. Trastuzumab is delivered once at a dose of 10mg/kg/day via intraperitoneal injection on the first day of the study. Lapatinib is administered daily at a doseof 100 mg/kg/day by oral gavage for 7 consecutive day

18、s. The selected doses are equivalent to those used inthe clinics. On day 8, anesthesia is induced by a single intraperitoneal injection of ketamine and xylazine (50and 5 mg/kg, respectively). The blood samples are collected and the hearts are removed for biochemicalanalysis.MCE has not independently

19、 confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 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: eaaq1093. Oncogene. 2016 Jun 9;35(23):2961-70.See more customer valid

20、ations on HYPERLINK / www.MedChemEREFERENCES1. Rusnak DW, et al. The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on thegrowth of human normal and tumor-derived cell lines in vitro and in vivo. Mol Cancer Ther. 2001 Dec;1(2):85-942. ONeill F, et al. Gene expression changes as markers of early lapatinib response in a panel of breast cancer cell lines. Mol Cancer. 2012Jun 18;11(1):41.3. Eryilmaz U, e