Lapatinib

Catalog No.S2111 Batch:S211107

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Technical Data

Formula

C29H26ClFN4O4S
Molecular Weight 581.06 CAS No. 231277-92-2
Solubility (25°C)* In vitro 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Lapatinib 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.
Targets
ErbB2 [1]
(Cell-free assay)		 EGFR [1]
(Cell-free assay)		 ErbB4 [1]
(Cell-free assay)
9.2 nM 10.8 nM 367 nM
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]

Protocol (from reference)

Kinase Assay:[1]
  • 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.
Cell Assay:[1]
  • Cell lines

    HFF, MCF-7, T47D, A-431, HN5, BT474, N87, CaLu-3, HB4a, and HB4a c5.2 cells

  • Concentrations

    Dissolved in DMSO, final concentrations ~100 μM

  • Incubation Time

    72 hours

  • Method

    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.
Animal Study:[1]
  • Animal Models

    CD-1 nude female mice implanted s.c. with HN5 cells, and C.B-17 SCID female mice implanted s.c. with BT474 cells

  • Dosages

    ~100 mg/kg

  • Administration

    Orally twice daily

Customer Product Validation

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]

Data from [Acta Pharmacol Sin, 2013, 10.1038/aps.2013.124]

Selleck's Lapatinib has been cited by 536 publications

Tumor-acquired somatic mutation affects conformation to abolish ABCG2-mediated drug resistance [ Drug Resist Updat, 2024, 73:101066] PubMed: 38387283
RAB22A sorts epithelial growth factor receptor (EGFR) from early endosomes to recycling endosomes for microvesicles release [ J Extracell Vesicles, 2024, 13(7):e12494] PubMed: 39051763
EGFR and HER2 hyper-activation mediates resistance to endocrine therapy and CDK4/6 inhibitors in ER+ breast cancer [ Cancer Lett, 2024, 593:216968] PubMed: 38788968
Cell-specific models reveal conformation-specific RAF inhibitor combinations that synergistically inhibit ERK signaling in pancreatic cancer cells [ Cell Rep, 2024, 43(9):114710] PubMed: 39240715
Targeting rapid TKI-induced AXL upregulation overcomes adaptive ERK reactivation and exerts antileukemic effects in FLT3/ITD acute myeloid leukemia [ Mol Oncol, 2024, 10.1002/1878-0261.13749] PubMed: 39395205
Peptidylarginine deiminase 3 modulates response to neratinib in HER2 positive breast cancer [ Oncogenesis, 2024, 13(1):30] PubMed: 39097594
Identification of kinase modulators as host-directed therapeutics against intracellular methicillin-resistant Staphylococcus aureus [ Front Cell Infect Microbiol, 2024, 14:1367938] PubMed: 38590439
Duloxetine enhances the sensitivity of non-small cell lung cancer cells to EGFR inhibitors by REDD1-induced mTORC1/S6K1 suppression [ Am J Cancer Res, 2024, 14(3):1087-1100] PubMed: 38590408
Targeting Tyro3, Axl, and MerTK Receptor Tyrosine Kinases Significantly Sensitizes Triple-Negative Breast Cancer to CDK4/6 Inhibition [ Cancers (Basel), 2024, 16(12)2253] PubMed: 38927958
Neratinib plus dasatinib is highly synergistic in HER2-positive breast cancer in vitro and in vivo [ Transl Oncol, 2024, 49:102073] PubMed: 39191139

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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