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100mg |
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250mg |
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500mg |
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1g |
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2g |
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Lapatinib Ditosylate (formerly GW-572016, GW572016; trade names Tykerb and Tyverb) is an orally bioavailable medication acting as an EGFR (epidermal growth factor receptor) and ErbB2 inhibitor with antineoplastic activity. In cell-free experiments, it inhibits EGFR and ErbB2 with IC50s of 10.8 and 9.2 nM, respectively. The FDA has approved this medication for the treatment of solid tumors, including breast cancer.
Targets |
ErbB2 (IC50 = 9.2 nM); EGFR (IC50 = 10.8 nM); ErbB4 (IC50 = 367 nM)
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ln Vitro |
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ln Vivo |
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Enzyme Assay |
The process of measuring the inhibition of phosphorylation of a peptide substrate yields the IC50 values for inhibition of enzyme activity. The EGFR and ErbB2 intracellular kinase domains are isolated using a baculovirus expression system. In round-bottomed polystyrene 96-well plates, EGFR and ErbB2 reactions are carried out with a final volume of 45 μL. The reaction mixtures consist of the following components: 50 μM Peptide A [Biotin-(amino hexonoic acid)-EEEEYFELVAKKK-CONH2], 1 mM dithiothreitol, 2 mM MnCl2, 10 μM ATP, 1 μCi of [γ33P] ATP/reaction, and 1 μL of DMSO containing serial dilutions of Lapatinib starting at 10 μM. The indicated purified type-1 receptor intracellular domain is added to start the reaction. One pmol of added enzyme is used for each reaction (20 nM). After 10 minutes at 23°C, 45 μL of 0.5% phosphoric acid in water is added to stop the reaction. The 75 μL of the finished reaction mix is put onto phosphocellulose filter plates. The plates undergo three rounds of filtering and washing with 200 μL of 0.5% phosphoric acid. Each well receives 50 μL of the scintillation cocktail, and the assay is measured using a Packard Topcount. 10-point dose-response curves are used to calculate IC50 values.
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Cell Assay |
Lapatinib is applied to cells at different concentrations for a duration of 72 hours. Staining with methylene blue yields an estimate of the relative cell number. Using a Spectra microplate reader, the absorbance at 620 nm is measured. By using propidium iodide staining, antibody detection of incorporated BrdUrd, and propidium iodide staining, cell death and cell cycle analysis are evaluated.
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Animal Protocol |
CD-1 nude female mice implanted s.c. with HN5 cells, and C.B-17 SCID female mice implanted s.c. with BT474 cells
~100 mg/kg Orally twice daily |
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References |
Molecular Formula |
C43H42CLFN4O10S3
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Molecular Weight |
925.46
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Exact Mass |
924.1735629
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Elemental Analysis |
C, 55.81; H, 4.57; Cl, 3.83; F, 2.05; N, 6.05; O, 17.29; S, 10.39
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CAS # |
388082-77-7
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Related CAS # |
Lapatinib;231277-92-2;Lapatinib ditosylate monohydrate;388082-78-8;Lapatinib tosylate;1187538-35-7
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Appearance |
Yellow solid powder
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SMILES |
CC1=CC=C(C=C1)S(=O)(=O)O.CC1=CC=C(C=C1)S(=O)(=O)O.CS(=O)(=O)CCNCC1=CC=C(O1)C2=CC3=C(C=C2)N=CN=C3NC4=CC(=C(C=C4)OCC5=CC(=CC=C5)F)Cl
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InChi Key |
UWYXLGUQQFPJRI-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C29H26ClFN4O4S.2C7H8O3S/c1-40(36,37)12-11-32-16-23-7-10-27(39-23)20-5-8-26-24(14-20)29(34-18-33-26)35-22-6-9-28(25(30)15-22)38-17-19-3-2-4-21(31)13-19;2*1-6-2-4-7(5-3-6)11(8,9)10/h2-10,13-15,18,32H,11-12,16-17H2,1H3,(H,33,34,35);2*2-5H,1H3,(H,8,9,10)
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Chemical Name |
N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine;4-methylbenzenesulfonic acid
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Synonyms |
GSK 572016; Trade name: Tykerb.GW2016; GSK 572016 ditosylate; GW-2016 ditosylate; GSK-572016 ditosylate; GSK-572016; GW-2016; GSK572016 ditosylate; GW2016 ditosylate; GW 2016; Lapatinib ditosylate; SK572016; GW 2016; Lapatinib
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.33 mg/mL (2.52 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 23.3 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.33 mg/mL (2.52 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 23.3 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 2% DMSO+30% PEG 300+ddH2O: 10 mg/mL |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.0805 mL | 5.4027 mL | 10.8054 mL | |
5 mM | 0.2161 mL | 1.0805 mL | 2.1611 mL | |
10 mM | 0.1081 mL | 0.5403 mL | 1.0805 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT02101905 | Active Recruiting |
Drug: Lapatinib Drug: Lapatinib Ditosylate |
Gliosarcoma Mixed Glioma |
National Cancer Institute (NCI) |
March 13, 2014 | Phase 1 |
NCT01273610 | Active Recruiting |
Drug: Lapatinib Drug: Trastuzumab |
Breast Neoplasms HER2/Neu Positive |
City of Hope Medical Center | April 20, 2011 | Phase 2 |
NCT00999804 | Active Recruiting |
Drug: Lapatinib Drug: Letrozole |
Breast Cancer | Baylor Breast Care Center | October 2011 | Phase 2 |
NCT00680901 | Active Recruiting |
Drug: Lapatinib Drug: Placebo |
Neoplasms, Gastrointestinal Tract | Novartis Pharmaceuticals | June 4, 2008 | Phase 3 |
NCT00470704 | Active Recruiting |
Drug: Lapatinib Drug: Herceptin |
Breast Cancer | Nancy Lin, MD | May 14, 2007 | Phase 2 |
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