Lapatinib (GW-572016) Ditosylate
Molecular Weight(MW): 925.46
Lapatinib (GW-572016) Ditosylate is a potent EGFR and ErbB2 inhibitor with IC50 of 10.8 and 9.2 nM in cell-free assays, respectively.
Cited by 52 Publications
7 Customer Reviews
Combination of NVP-AEW541 and lapatinib cooperatively inhibits the growth of NVP-AEW541 resistant murine rhabdomyosarcoma primary cell cultures with Igf1r/Her2 complexes. Cell viability assay for Naïve, untreated (U20325; A) and NVP-AEW541 innately resistant mouse rhabdomyosarcoma primary culture (U44676; B) treated with varying concentrations of NVP-AEW541, lapatinib, or a combination of both. Naïve cells (U20325) were sensitive to NVP-AEW541, but lapatinib had no cooperativity. In contrast, NVP-AEW541 at moderate doses increased cell growth in resistant cell cultures (U44676). However, this paradoxical effect was reduced by the addition of lapatinib, although lapatinib treatment alone had very little effect. C, the NVP-AEW541 resistant primary tumor cell line (U44676) was treated with DMSO, 5 μmol/L lapatinib, 5 μmol/L NVP-AEW541, and a combination of 5 μmol/L NVP-AEW541+lapatinib for 25 minutes and Western blot analysis was done on lysates for p-Igf1r and p-Her2.
Mol Cancer Ther 2011 10:697-707. Lapatinib (GW-572016) Ditosylate purchased from Selleck.
(B-C) LNCaP (B) and LNCaP-AI (C) cells were transiently transfected with sPLA2-IIa(-800)-Luc (0.5 lg). The cells were then treated with Erlotinib (20 μM), Gefitinib (20 μM), Lapatinib (20 μM), CI-1033 (8 μM), LY294002 (20 μM) and Bortezomib (20 μM) without or with EGF (100 ng/ml) for 24 h. Luciferase assay was performed according to a standard protocol with Renilla luciferase as an internal control. Data are presented as the mean (±SD) of duplicate values of a representative experiment that was independently repeated for five times.
Carcinogenesis 2010 31, 1948–1955 . Lapatinib (GW-572016) Ditosylate purchased from Selleck.
LNCaP-AI cells were starved in 1% stripped medium for 24 h. The cells were then treated with Erlotinib (20 μM), Gefitinib (20 μM), Lapatinib (20 μM), CI-1033 (8 μM), LY294002 (20 μM) and Bortezomib (20 μM) for 24 h. Cell culture medium was collected from each sample and subjected to ELISA for sPLA2-IIa. The condition medium samples were diluted 10 times for ELISA. Average of duplicate samples was converted to nanogram per milliliter against standard curve. The data represent one of five repeated experiments.
Carcinogenesis 2010 31, 1948–1955. Lapatinib (GW-572016) Ditosylate purchased from Selleck.
Impact of the TKI erlotinib, lapatinib, dasatinib, and sorafenib on the viability of MDS/AML cells. MOLM-13 (A) and HL-60 (B) cells were incubated with the indicated doses (given in mM below the x-axis) of the 4 TKI, and cellular viability was assessed by MTT assay after 24, 48 and 72 h of incubation. Changes in viability are given as percentage of cells as compared to non-treated control samples. This experiment was repeated at least three times, yielding comparable results. Graphs show representative results of one experiment carried out in duplicates (mean standard deviation).
Biochem Pharmacol 2011 82, 1457-1466. Lapatinib (GW-572016) Ditosylate purchased from Selleck.
Capacity of the TKI to overcome the AML-typical differentiation blockage. The myeloid cell lines MOLM-13 and HL-60 were incubated for 6 days with 0.01% DMSO (serving as a negative solvent control), 1 μM of ATRA (serving as a positive control), as well as with the indicated doses of the four TKI. (A) Representative May-Gruenwald-Giemsa staining of MOLM-13 cells, (B) quantitation of the percentage of MOLM-13 cells exhibiting at least two morphological signs of differentiation (that is a decrease in cytoplasmic basophilia, a reduction of the nucleo-cytoplasmic ratio, appearance of nuclear lobulation and/or cytoplasmic granules). Percentages were evaluated by examining at least 100 cells/condition; (C) representative FACS overlays of MOLM-13 cells depicting TKI-induced CD11b expression (black line) as compared to the isotype (shaded grey); (D) quantitation of TKI-induced CD11b-expression in MOLM-13 cells; (E) representative slides depicting morphology/staining of MOLM-13 cells assessed in the NBT-reduction assay; (F) respective quantitative assessment demonstrating the NBT-reducing capacity under the different drugs; (G) representative May-Gruenwald-Giemsa staining of HL-60 cells.
Biochem Pharmacol 2011 82, 1457-1466. Lapatinib (GW-572016) Ditosylate purchased from Selleck.
Inhibition of signaling pathway activation in lung tumor cell lines by kinase inhibitors. Lung tumor cells were cultured in 10% FBS until reaching ∼80% confluence and then the cells were starved in serum-free medium for overnight, followed by 4-hour treatment with the inhibitors. Cell lysates were then prepared and used for determination of the pathway activation signals by the CEER assay.
Int J Proteomics 2011 2011, 215496. Lapatinib (GW-572016) Ditosylate purchased from Selleck.
Purity & Quality Control
Choose Selective HER2 Inhibitors
|Description||Lapatinib (GW-572016) Ditosylate is a potent EGFR and ErbB2 inhibitor with IC50 of 10.8 and 9.2 nM in cell-free assays, respectively.|
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. 
|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. |
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.
|In vitro||DMSO||100 mg/mL (108.05 mM)|
|Water||slightly soluble or insoluble|
|Ethanol||slightly soluble or insoluble|
|In vivo||Add solvents individually and in order:
2% DMSO+30% PEG 300+ddH2O
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Clinical Trial Information
|NCT Number||Recruitment||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT00107003||Completed||Glioma|Brain Tumor|Glioblastoma Multiforme|GBM|Gliosarcoma|GS||National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC)||March 30, 2005||Phase 2|
|NCT00251433||Active, not recruiting||Neoplasms, Breast||Novartis Pharmaceuticals|Novartis||September 26, 2005||Phase 1|
|NCT01306045||Recruiting||Carcinoma, Non-Small-Cell Lung|Carcinoma, Small Cell Lung|Carcinoma, Thymic||National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC)||January 21, 2011||Phase 2|
|NCT03052634||Recruiting||Advanced Breast Cancer||RemeGen||November 2016||Phase 1|Phase 2|
|NCT02836847||Recruiting||Cholangiocarcinoma of the Extrahepatic Bile Duct|Gallbladder Cancer||Shanghai Jiao Tong University School of Medicine|Xinhua Hospital, Shanghai Jiao Tong University School of Medicine|Ruijin Hospital|RenJi Hospital|Eastern Hepatobiliary Surgery Hospital|Huashan Hospital||July 2016||Phase 2|
|NCT02650752||Recruiting||Metastatic Breast Cancer|Central Nervous System (CNS) Metastases||Memorial Sloan Kettering Cancer Center|Queens Cancer Center of Queens Hospital|University of Michigan||January 2016||Phase 1|
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