Lapatinib (GW-572016) Ditosylate

Catalog No.S1028

For research use only.

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 (GW-572016) Ditosylate Chemical Structure

CAS No. 388082-77-7

Selleck's Lapatinib (GW-572016) Ditosylate has been cited by 103 publications

Purity & Quality Control

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Biological Activity

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.
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 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. [1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HN5 cell line MXPQdo9tcW[ncnH0bY9vKGG|c3H5 MlmzRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCKTkWgZ4VtdCCuaX7lMEBKSzVyPUCuNFI2KM7:TR?= Mn32QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTZ2OEO3O|IoRjF4NEizO|czRC:jPh?=
BT474 cell line M3v1PHBzd2yrZnXyZZRqd25iYYPzZZk> NUPaSmZXSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDCWFQ4PCClZXzsJIxqdmVuIFnDOVA:OC5yMkWg{txO NIrNcFc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zNkS4N|c4Oid-MU[0PFM4PzJ:L3G+
HN5 cell NEHBfYlIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NVnXXXVmUW6qaXLpeIlwdiCxZjDIUlUh[2WubDDndo94fGhiYX\0[ZIhPzJiaILzMEBKSzVyPUCuNVIh|ryP MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPjd5N{SxNEc,OTZ5N{e0NVA9N2F-
BT474 cell M3rkOGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NVf3SFhzUW6qaXLpeIlwdiCxZjDCWFQ4PCClZXzsJIdzd3e2aDDh[pRmeiB5MjDodpMtKEmFNUC9NE4xQCEQvF2= NH;CbXM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zNke3O|QyOCd-MU[3O|c1OTB:L3G+
N87 cell NVWzN3NHT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NETJRYRKdmirYnn0bY9vKG:oIF64O{Bk\WyuIHfyc5d1cCCjZoTldkA4OiCqcoOsJGlEPTB;MD6wPEDPxE1? NWnVcGtjRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMU[3O|c1OTBpPkG2O|c4PDFyPD;hQi=>
HFF cell NX3HUXp5T3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MYPJcohq[mm2aX;uJI9nKEiIRjDj[YxtKGe{b4f0bEwhUUN3ME25Mlkh|ryP M33mcFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF4N{e3OFExLz5zNke3O|QyODxxYU6=
BT474 NITQV3VCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= NEG5cWRCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFLUOFc1KGOnbHzzJI93\XKneIDy[ZN{cW6pIFXyRlItKEmFNUC9NE4xOjYQvF2= MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDZ3M{OzN{c,OTh4NUOzN|M9N2F-
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Hep3B2 NW\qTHF7SW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= NFf0UotCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFjldFNDOiClZXzsd{Bi\nSncjDodpMh[nliQWTQJINwdnSnboSgZZN{[XluIFnDOVA:PS52Od88US=> M3XvOFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJyMUSzO|c5Lz5{MEG0N|c4QDxxYU6=
HepG2 M32yfmFvfGmycn;sbYZmemG2aY\lJIF{e2G7 NVXlOHFySW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDI[ZBIOiClZXzsd{Bi\nSncjDodpMh[nliQWTQJINwdnSnboSgZZN{[XluIFnDOVA:Pi5{N988US=> M1f4WVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJyMUSzO|c5Lz5{MEG0N|c4QDxxYU6=
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A431 M3zDdWZ2dmO2aX;uJIF{e2G7 Mmi0TY5pcWKrdHnvckBw\iCHR1\SJIlvfHKjY3XscJVt[XJicHjvd5Bpd3K7bHH0bY9vKGmwIHj1cYFvKEF2M{GgZ4VtdHNiYomgSWxKW0FuIFnDOVA:OC5yNUNOwG0> NInmO2o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MEO0OlY2PSd-MkCzOFY3PTV:L3G+
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MIAPaCa M4L5dGZ2dmO2aX;uJIF{e2G7 M1XPSWlvcGmkaYTpc44hd2ZiRWLCZlIheGixc4Doc5J6dGG2aX;uJIlvKGi3bXHuJG1KSVCjQ3GgZ4VtdHNiYomgSWxKW0FuIFnDOVA:OC5zNN88US=> M1v4UVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJyOEG3OVI{Lz5{MEixO|UzOzxxYU6=
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CAL27 NXHGN2c3S3m2b4TvfIlkcXS7IHHzd4F6 MmDlR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gR2FNOjdiY3XscJMhd3[ncnX4dJJme3OrbnegSWdHWiCkeTDy[ZNignW{aX6g[JlmKHKnZIXjeIlwdiCjc4PhfUwhUUN3ME2wMlAxP87:TR?= NGjldHo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUC4NFYzQSd-MkGwPFA3Ojl:L3G+
CAL27 M4Hw[mZ2dmO2aX;uJIF{e2G7 MVOxOkBpenN? NXW1fJpLUW6qaXLpeIlwdiCxZjDFS2YucW6mdXPl[EBGT0[UIIDoc5NxcG:{eXzheIlwdiCrbjDoeY1idiCFQVyyO{Bk\WyuczDveoVz\XiycnXzd4lv\yCHR1\SJIFnfGW{IEG2JIhzeyCkeTDX[ZN1\XKwIHLsc5QtKEmFNUC8NE4xOzMQvF2= MUW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTB6ME[yPUc,OjFyOEC2Nlk9N2F-
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HCC2218 cell NYrpT5djT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MUDJcohq[mm2aX;uJI9nKGi3bXHuJGhESzJ{MUigZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2wMlA2OzJ4IN88US=> MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1OVQwLz6VQV7HSXI9N2F-
LB2241-RCC cell M{TJbGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NWXhfXVVUW6qaXLpeIlwdiCxZjDoeY1idiCOQkKyOFEuWkOFIHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;MT6xOVQxOyEQvF2= MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1OVQwLz6VQV7HSXI9N2F-
LB996-RCC cell NFj2cGtIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NX3Uco5kUW6qaXLpeIlwdiCxZjDoeY1idiCOQkm5Ok1TS0NiY3XscEBoem:5dHigbY4h[SClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OD1zLkO2NlI5KM7:TR?= NWn5O3ZqRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTV2Lze+V2FPT0WUPD;hQi=>
LC-1F cell NF74T4NIem:5dHigbY5pcWKrdHnvckBie3OjeR?= M{XXN2lvcGmkaYTpc44hd2ZiaIXtZY4hVENvMV[gZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2xMlM5OjR2IN88US=> MnH3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVU1Nyd-U1HOS2VTRC:jPh?=
LS-513 cell NGTzVWRIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NWX2d3ZsUW6qaXLpeIlwdiCxZjDoeY1idiCOUz21NVMh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0{NjRyMESxJO69VQ>? M2T5TVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU2PC9pPmPBUmdGWjxxYU6=
Assay
Methods Test Index PMID
Western blot p-ErbB2 / t-ErbB2 / p-Akt / t-Akt / p-Erk / t-Erk ; pEGFR / EGFR / p-mTOR / mTOR / PARP / c-PARP 25238247 28938602
Growth inhibition assay Cell viability 24947784
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. [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 Research:[1]
  • Cell lines: HFF, MCF-7, T47D, A-431, HN5, BT474, N87, CaLu-3, HB4a, and HB4a c5.2
  • 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.
  • (Only for Reference)
Animal Research:[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
  • (Only for Reference)

Solubility (25°C)

In vitro

DMSO 100 mg/mL
(108.05 mM)
Water Insoluble
Ethanol Insoluble

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
2% DMSO+40% PEG 300+5% Tween 80+53% ddH2O
For best results, use promptly after mixing.

1.25 mg/mL

* 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.

Chemical Information

Molecular Weight 925.46
Formula

C29H26ClFN4O4S.2C7H8O3S

CAS No. 388082-77-7
Storage 3 years -20°C powder
2 years -80°C in solvent
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

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04608409 Recruiting Drug: Lapatinib and Paclitaxel Ovarian Cancer Frederick R. Ueland M.D.|University of Kentucky November 16 2020 Phase 1
NCT03075995 Unknown status Other: hight-fat breakfast Breast Cancer Sun Yat-sen University April 12 2017 Not Applicable
NCT02338245 Completed Drug: ASLAN001|Drug: Lapatinib|Drug: Capecitabine Metastatic Breast Cancer Aslan Pharmaceuticals December 29 2014 Phase 2
NCT02294786 Terminated Drug: Lapatinib|Drug: Capecitabine|Drug: Octreotide Cancer Novartis Pharmaceuticals|Novartis December 17 2014 Phase 2
NCT02158507 Active not recruiting Drug: Combination of Veliparib + Lapatinib Metastatic Triple Negative Breast Cancer University of Alabama at Birmingham|Scariot Foundation|GlaxoSmithKline|AbbVie September 2014 Not Applicable
NCT01782651 Completed Drug: Lapatinib plus capecitabine Neoplasms Breast GlaxoSmithKline August 2014 --

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

Question 1:
If I need to use S1028 for treating tumor-bearing mice with injection, how could I prepare the solution?

Answer:
S1028 Lapatinib Ditosylate can be dissolved in 2% DMSO/30% PEG 300/ddH2O at 10 mg/ml as clear solution.

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