Name: Lapatinib
Brand: BOC Sciences
Price: 168 USD
Availability: MadeToOrder

Purity

>98%

Solubility

Yellow solid. Solubility at 25 eg C (mg/mL): 0.007 in water; 0.001 in 0.1 N HCl /Lapatinib ditoluenesulfonate monohydrate/

Application

Antineoplastic agents; protein kinase inhibitors

IUPACName

N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine

Synonyms

GW-572016; GSK-572016; GSK 572016

InChI Key

BCFGMOOMADDAQU-UHFFFAOYSA-N

InChI

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)

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

Mechanism

Target: This ligand targets EGFR/ERBB1 and HER2/ERBB2 tyrosine kinase domains in biochemical or cellular target-engagement studies.

Mechanism of Action: Used as the target-protein recognition element, this ligand provides the binding interface for EGFR/ERBB1 and HER2/ERBB2 tyrosine kinase domains. In PROTAC design, a derivatizable position on the ligand can be connected through an optimized linker to an E3 ligase ligand, such as a CRBN, VHL, or IAP recruiter, while preserving productive target engagement. The resulting bifunctional molecule brings EGFR/ERBB1 into proximity with the recruited E3 ligase, enabling ternary-complex formation. If the complex has favorable geometry and residence time, target lysine ubiquitination is promoted, leading to proteasome-dependent degradation in experimental systems.

Applications

• EGFR/HER2 PROTAC Targeting: Lapatinib can be used as a kinase-binding warhead to recruit EGFR and HER2 in PROTAC designs. By coupling it to an E3 ligase ligand, researchers can evaluate whether ternary complex formation drives ubiquitination and selective degradation of EGFR/HER2, enabling pathway suppression beyond reversible kinase inhibition.

• Receptor Degradation Studies: In targeted protein degradation workflows, Lapatinib-based PROTACs can be applied to quantify degradation kinetics of EGFR/HER2 in cancer cell models. This supports mechanistic studies comparing proteasome-dependent loss, residence-time effects, and degradation selectivity across receptor family members.

• Ternary Complex Optimization: Lapatinib-derived warheads are suitable for PROTAC optimization aimed at improving ternary complex stability with EGFR/HER2 and an E3 ligase. Systematic linker and attachment-site variation can be used to tune cooperativity, thereby enhancing ubiquitination efficiency and increasing degradation potency.

• Resistance Mechanism Probing: Lapatinib-based PROTACs can help dissect resistance mechanisms where kinase inhibition fails. By degrading EGFR/HER2 rather than only blocking signaling, researchers can test whether degradation circumvents compensatory phosphorylation, receptor reactivation, or partial target engagement in resistant phenotypes.

1.A phase I/II trial of GW572016 (lapatinib) in recurrent glioblastoma multiforme: clinical outcomes, pharmacokinetics and molecular correlation

Brian Thiessen • Clinton Stewart • Ming Tsao • Suzanne Kamel-Reid. Cancer Chemother Pharmacol (2010) 65:353–361

We were unable to demonstrate any beneWt of lapatinib in the 17 patients enrolled in the phase II arm of this trial. Only four patients demonstrated stable disease and 13 patients showed early progression, thus, even in the absence of response, there was no signal of activity in terms of delay in progression in meaningful numbers of patients. Because of these results, as per protocol, the phase II portion of the trial was closed to accrual. At that time, seven patients had been enrolled into the phase I arm of the trial and although a recommended dose had not been identiWed, the lack of eYcacy of the agent made the pursuit of a recommended dose in this population no longer relevant. In both EIAED and non-EIAED patients, we were able to con- Wrm that lapatinib was a well tolerated agent. No Grade 4 toxicities were seen and no cardiac toxicity was identiWed. There are several possible reasons for the lack of eYcacy in this tumor group. Lapatinib may perform better in cells that have both ErB-1 and ErbB-2 expression rather than isolated ErbB-1 overexpression. In fact, lapatinib may bind only to inactive/intermediate form of EGFR and constitutively active EGFR (i.e., EGFRvIII mutation) may not be inhibited at all.

2.Cost-effectiveness of lapatinib plus capecitabine in women with HER2+ metastatic breast cancer who have received prior therapy with trastuzumab

Thomas E. Delea • Paul Tappenden • Oleg Sofrygin • Dominy Browning. Eur J Health Econ (2012) 13:589–603

EGF100151 was a phase III randomized controlled trial to evaluate the efﬁcacy and safety of combined therapy with lapatinib, an orally administered dual inhibitor of ErbB1 and HER2, plus capecitabine versus capecitabine monotherapy in women with HER2-positive metastatic breast cancer previously treated with an anthracycline and a taxane (for adjuvant and/or metastatic disease) and trastuzumab (for metastatic disease) [10]. Patients in the combination therapy arm received lapatinib 1,250 mg daily continuously plus capecitabine 2,000 mg/m² daily for 14 days every 3 weeks. Those in the capecitabine monotherapy arm received capecitabine 2,500 mg/m² daily for 14 days every 3 weeks. Approximately one-half of subjects had received C4 prior lines of chemotherapy prior to randomization. Based on the recommendation of an independent data-monitoring committee reviewing data up to 15 November 2005, enrolment into the trial was discontinued and crossover to lapatinib plus capecitabine was offered to women receiving capecitabine monotherapy as of 3 April 2006.

3.Pooled analysis of diarrhea events in patients with cancer treated with lapatinib

John P. Crown, Harold A. Burris III, Fran Boyle , Suzanne Jones, Maria Koehler. Breast Cancer Res Treat (2008) 112:317–325

Lapatinib (Tykerb®/Tyverb®; GlaxoSmithKline, Philadelphia, PA) is an oral, dual tyrosine kinase inhibitor targeting both EGFR (ErbB1) and HER2 (ErbB2) receptors. Lapatinib is approved in the United States, Switzerland, Australia, and several other international markets for the treatment of advanced or metastatic breast cancer in patients with HER2-positive tumors who have progressed on treatment regimens containing an anthracycline, a taxane, and trastuzumab. Lapatinib is clinically active as a single agent or in combination with various chemotherapy agents in patients with HER2-positive breast cancer and other solid tumors.

4.Randomized phase II study of lapatinib plus capecitabine or lapatinib plus topotecan for patients with HER2-positive breast cancer brain metastases

Nancy U. Lin • Wolfgang Eierman • Richard Greil • Mario Campone. J Neurooncol (2011) 105:613–620

Lapatinib is an orally bioavailable, 4-aniloquinazoline tyrosine kinase inhibitor of the epidermal growth factor and HER2. In animal models, lapatinib inhibits CNS outgrowth of HER2-positive cell lines. CNS therapeutic levels have been demonstrated in tumor resection specimens in patients with glioblastoma multiforme. Two phase 2 trials have evaluated lapatinib monotherapy in patients with progressive HER2-positive, brain metastases.

ConcentrationVolumeMass	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
50 mM	0.0344 mL	0.1721 mL	0.3442 mL

Lapatinib is a multi-kinase target ligand intended for use as the target-engaging component or reference ligand in PROTAC discovery workflows. Its known small-molecule recognition profile enables rational linker-vector evaluation and comparative degrader design. This molecule is described in detail below.

Structure: The structure of Lapatinib is characterized by primary or secondary amine/basic nitrogen centers; amide/urea/sulfonamide hydrogen-bonding motifs; halogenated aryl/heteroaryl ring system; heteroaromatic protein-recognition scaffold. These features provide defined hydrogen-bonding, hydrophobic, and steric elements that can support affinity retention while enabling analogue-based linker-vector selection.

Reactivity: The amine/basic nitrogen-containing motif can be evaluated for acylation, sulfonylation, alkylation, or carbamate/urea linker installation when that vector is solvent exposed. For PROTAC construction, the POI ligand can be paired with CRBN ligands such as thalidomide, pomalidomide, or lenalidomide analogues, VHL ligands such as VH032 derivatives, or less common IAP/MDM2/cIAP-recruiting ligands, with alkyl, PEG, piperazine, triazole, or amide linkers screened for ternary-complex formation. In practice, incorporation into PROTACs should begin from derivatives that preserve the reported binding pharmacophore, followed by systematic variation of linker length, polarity, rigidity, and exit-vector geometry to optimize target engagement, E3 recruitment, and cellular degradation readouts.

HPLC

HNMR

Hi, I was just wondering how Lapatinib induces mitochondrial dysfunction to enhance oxidative stress.

OK! Lapatinib induces mitochondrial dysfunction to enhance oxidative stress and ferroptosis in doxorubicin-induced cardiomyocytes via inhibition of PI3K/AKT signaling pathway.

15/6/2017

Hello! Which phase of the cell cycle can Lapatinib inhibit?

Hi, Lapatinib treatment results in induces G1 arrest in HN5 cells.

26/11/2018

We'd like to know that how Lapatinib alters the malignant phenotype of osteosarcoma cells.

Hello. Lapatinib alters the malignant phenotype of osteosarcoma cells via downregulation of the activity of the HER2-PI3K/AKT-FASN axis in vitro.

1/4/2021

block tumor xenograft growth

This product works pretty well. Lapatinib treatment blocks tumor xenograft growth of the HN5 cells in a dose-responsive manner, with complete inhibition of tumor growth at the higher dose.

16/12/2017

have a selective inhibition of the proliferation of human tumor cell lines

Lapatinib inhibited cell proliferation as expected. Great performance! Lapatinib treatment has a selective inhibition of the proliferation of human tumor cell lines.

8/2/2020

inhibit receptor autophosphorylation of EGFR

Chemical worked well in our experiments, happy with purchase. Lapatinib inhibits receptor autophosphorylation of EGFR and ErbB-2 in a dose-responsive manner.

7/11/2022

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It is commonly abbreviated as: C₁V₁ = C₂V₂