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Purity: ≥98%
Lapatinib (formerly GW572016, trade names Tykerb & Tyverb), usually used in the Ditosylate form, is a potent, orally bioavailable dual EGFR/ErbB2 inhibitor with potential anticancer activity. In cell-free assays, it inhibits the epidermal growth factor receptor (EGFR)/ErbB2 with an IC50 of 10.8 and 9.2 nM, respectively. It is a drug that has FDA approval and is used to treat solid tumors such as breast cancer. The mechanism of action of lapatinib is the reversible inhibition of phosphorylation of EGFR, ErbB2, Erk-1, Erk-2, and AKT kinases.
| Targets |
EGFR (IC50 = 10.2 nM); ErbB2 (IC50 = 9.8 nM); ErbB4 (IC50 = 367 nM)
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| ln Vitro |
Lapatinib exhibits >300-fold selectivity for EGFR and ErbB2 over other kinases, including c-Src, c-Raf, MEK, ERK, c-Fms, CDK1, CDK2, p38, Tie-2, and VEGFR2. It also weakly inhibits the activity of ErbB4 with an IC50 of 367 nM. With an IC50 of 170 nM and 80 nM, respectively, in HN5 cells and 210 nM and 60 nM, respectively, in BT474 cells, lapatinib significantly inhibits receptor autophosphorylation of EGFR and ErbB2 in a dose-dependent manner. Lapatinib inhibits the growth of both EGFR- and ErbB2-overexpressing cells, in contrast to OSI-774 and Iressa (ZD1839), which preferentially inhibit the growth of the EGFR-overexpressing cells. Lapatinib exhibits approximately 100-fold selectivity over normal fibroblast cells and shows higher inhibitory activity against EGFR- or ErbB2-overexpressing cells (IC50 of 0.09-0.21 μM) as compared to cells expressing low levels of EGFR or ErbB2. Lapatinib strongly induces G1 arrest in HN5 cells and apoptosis in BT474 cells, which are linked to inhibition of AKT phosphorylation. It also potently inhibits the outgrowth of EGFR-overexpressing HN5 and A-431 cells, as well as ErbB2-overexpressing BT474 and N87 cells.[1]
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| ln Vivo |
Lapatinib (~100 mg/kg) given orally twice a day significantly and dose-dependently inhibits the growth of HN5 and BT474 xenografts.[1]
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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 |
For 72 hours, cells are exposed to different lapatinib concentrations. Methylene blue staining is used to estimate the relative number of cells. A Spectra microplate reader is used to measure the absorbance at 620 nm. Propidium iodide staining, antibody detection of incorporated BrdUrd, and propidium iodide staining are used to analyze cell death and the cell cycle.
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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 |
| References |
| Molecular Formula |
C29H26CLFN4O4S
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|---|---|
| Molecular Weight |
581.06
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| Exact Mass |
580.13
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| Elemental Analysis |
C, 59.94; H, 4.51; Cl, 6.10; F, 3.27; N, 9.64; O, 11.01; S, 5.52
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| CAS # |
231277-92-2
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| Related CAS # |
Lapatinib ditosylate;388082-77-7;Lapatinib ditosylate monohydrate;388082-78-8;Lapatinib-d4;1184263-99-7;Lapatinib tosylate;1187538-35-7;Lapatinib-d7 dihydrochloride;Lapatinib-d5;2748212-14-6;Lapatinib-d4-1;1184264-15-0
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| Appearance |
Solid powder
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| SMILES |
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 |
BCFGMOOMADDAQU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H26ClFN4O4S/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/h2-10,13-15,18,32H,11-12,16-17H2,1H3,(H,33,34,35)
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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
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| Synonyms |
Lapatinib; Lapatinib ditosylate; GW2016; gw572016; gw 572016;GW-2016; GW 2016; GW-572016; GSK572016; GSK 572016; gw-572016; Trade name: Tykerb
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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) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7210 mL | 8.6050 mL | 17.2099 mL | |
| 5 mM | 0.3442 mL | 1.7210 mL | 3.4420 mL | |
| 10 mM | 0.1721 mL | 0.8605 mL | 1.7210 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 |
| NCT00999804 | Active Recruiting |
Drug: Lapatinib Drug: Letrozole |
Breast Cancer | Baylor Breast Care Center | October 2011 | Phase 2 |
| NCT01273610 | Active Recruiting |
Drug: Lapatinib Drug: Trastuzumab |
Breast Neoplasms HER2/Neu Positive |
City of Hope Medical Center | April 20, 2011 | Phase 2 |
| NCT00470704 | Active Recruiting |
Drug: Lapatinib Drug: Herceptin |
Breast Cancer | Nancy Lin, MD | May 14, 2007 | Phase 2 |
| NCT03523585 | Active Recruiting |
Drug: Lapatinib Drug: Trastuzumab |
Breast Cancer | Daiichi Sankyo, Inc. | August 1, 2018 | Phase 3 |
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