Lapatinib

Details

Stereochemistry	ACHIRAL
Molecular Formula	C29H26ClFN4O4S
Molecular Weight	581.058
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CS(=O)(=O)CCNCC1=CC=C(O1)C2=CC3=C(C=C2)N=CN=C3NC4=CC(Cl)=C(OCC5=CC(F)=CC=C5)C=C4

InChI

InChIKey=BCFGMOOMADDAQU-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C29H26ClFN4O4S
Molecular Weight	581.058
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022059s007lbl.pdf
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800015425

Lapatinib is a small molecule and a member of the 4-anilinoquinazoline class of kinase inhibitors. It is present as the monohydrate of the ditosylate salt (trade name TYKERB). Lapatinib is dual inhibitor of the EGFR (epidermal growth factor receptor; also called HER1 or ErbB1) and HER2 receptor tyrosine kinases. Lapatinib was developed by GlaxoSmithKline, however, Novartis subsequently acquired all the rights to the drug from GlaxoSmithKline. TYKERB is indicated in combination therapy for the treatment of metastatic breast cancer that overexpresses the HER2 receptor.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Epidermal growth factor receptor erbB1 62 Target ID: CHEMBL203 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022059s007lbl.pdf	Inhibitor 8504		3.0 nM [Ki]
Receptor protein-tyrosine kinase erbB-2 35 Target ID: CHEMBL1824 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022059s007lbl.pdf	Inhibitor 8504		13.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Breast cancer 432 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022059s007lbl.pdf	Primary		Approved 8583	TYKERB Approved Use TYKERB® is indicated in combination with: •capecitabine for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab. Limitation of Use: Patients should have disease progression on trastuzumab prior to initiation of treatment with TYKERB in combination with capecitabine. •letrozole for the treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer that overexpresses the HER2 receptor for whom hormonal therapy is indicated. TYKERB in combination with an aromatase inhibitor has not been compared to a trastuzumab-containing chemotherapy regimen for the treatment of metastatic breast cancer. TYKERB, a kinase inhibitor, is indicated in combination with: (1) •capecitabine, for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab. Limitation of Use: Patients should have disease progression on trastuzumab prior to initiation of treatment with TYKERB in combination with capecitabine. •letrozole for the treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer that overexpresses the HER2 receptor for whom hormonal therapy is indicated. TYKERB in combination with an aromatase inhibitor has not been compared to a trastuzumab-containing chemotherapy regimen for the treatment of metastatic breast cancer. Launch Date 2007

C_max

Value	Dose	Co-administered	Analyte	Population
2.43 μg/mL DRUG LABEL https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/tykerb.pdf	1250 mg 1 times / day steady-state, oral dose: 1250 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		LAPATINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
36.2 μg × h/mL DRUG LABEL https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/tykerb.pdf	1250 mg 1 times / day steady-state, oral dose: 1250 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		LAPATINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
24 h DRUG LABEL https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/tykerb.pdf	1250 mg 1 times / day steady-state, oral dose: 1250 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		LAPATINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022059s007lbl.pdf			LAPATINIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
1250 mg 1 times / day steady, oral MTD Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24197661	unhealthy, 50 years (range: 30–78 years) Health Status: unhealthy Age Group: 50 years (range: 30–78 years) Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/24197661	DLT: Rash, Diarrhea... Dose limiting toxicities: Rash (grade 3, 2 patients) Diarrhea (grade 3, 2 patients) Hypoxia (grade 3, 1 patient) Pulmonary embolus (grade 4, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/24197661
1500 mg 1 times / day steady, oral Dose: 1500 mg, 1 times / day Route: oral Route: steady Dose: 1500 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24197661	unhealthy, 50 years (range: 30–78 years) Health Status: unhealthy Age Group: 50 years (range: 30–78 years) Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/24197661	DLT: Mucositis, Rash... Dose limiting toxicities: Mucositis (grade 3, 2 patients) Rash (grade 3, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/24197661
1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022059lbl.pdf	unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022059lbl.pdf	Disc. AE: Diarrhea... Other AEs: Diarrhea, Diarrhea... AEs leading to discontinuation/dose reduction: Diarrhea (grade 4, 1%) Other AEs: Diarrhea (all grades, 65%) Diarrhea (grade 3, 13%) Nausea (all grades, 44%) Nausea (grade 3, 2%) Vomiting (all grades, 26%) Vomiting (grade 3, 2%) Stomatitis (all grades, 14%) Dyspepsia (all grades, 11%) Dyspepsia (grade 3, <1%) Palmar-plantar erythrodysesthesia syndrome (all grades, 53%) Palmar-plantar erythrodysesthesia syndrome (grade 3, 12%) Rash (all grades, 28%) Rash (grade 3, 2%) Dermatitis acneiform (grade 3, <1%) Dry skin (all grades, 10%) Mucosal inflammation (all grades, 15%) Pain in extremity (all grades, 12%) Pain in extremity (grade 3, 1%) Back pain (all grades, 11%) Back pain (grade 3, 1%) Dyspnea (all grades, 12%) Dyspnea (grade 3, 3%) Insomnia (all grades, 10%) Insomnia (grade 3, <1%) Hepatotoxicity (severe\|grade 5) Bilirubin total increased (grade 3, 4%) Bilirubin total increased (grade 1-2, 41%) AST increased (grade 3, 2%) AST increased (grade 4, <1%) AST increased (grade 1-2, 46%) ALT increased (grade 3, 2%) ALT increased (grade 1-2, 35%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022059lbl.pdf
1800 mg 1 times / day steady, oral MTD Dose: 1800 mg, 1 times / day Route: oral Route: steady Dose: 1800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19052038	unhealthy, 60 years (range: 37 – 73 years) Health Status: unhealthy Age Group: 60 years (range: 37 – 73 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19052038	DLT: Diarrhea, Gamma GT increased... Other AEs: Stomatitis, Rash... Dose limiting toxicities: Diarrhea (grade 3, 2 patients) Gamma GT increased (grade 3, 1 patient) Other AEs: Stomatitis (grade 1, 1 patient) Rash (grade 2, 2 patients) Seborrheic dermatitis (grade 1, 1 patient) Paronychia (grade 1, 1 patient) Anorexia (grade 1, 3 patients) Lymphocyte count decreased (grade 1, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/19052038
1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022059lbl.pdf	unhealthy, 63 years Health Status: unhealthy Age Group: 63 years Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022059lbl.pdf	Other AEs: Hepatotoxicity, Bilirubin total increased... Other AEs: Hepatotoxicity (severe\|grade 5) Bilirubin total increased (grade 3, <1%) Bilirubin total increased (grade 4, <1%) Bilirubin total increased (grade 1-2, 20%) AST increased (grade 3, 6%) AST increased (grade 1-2, 47%) ALT increased (grade 3, 5%) ALT increased (grade 4, <1%) ALT increased (grade 1-2, 40%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022059lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 substrate 1946 inducer 1087	substrate 1193 inhibitor 2438 inducer 440	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 1057 P-gp 1741 CYP1A2 2153 CYP2C19 2057 UGT 45 BCRP 910 OATP1B1 1079 OAT3 747	P-gp 2052 CYP3A5 446 CYP2C8 810 CYP2C19 1119 CYP1A2 1197 CYP2B6 776 CYP2A6 626 CYP2E1 729 BCRP 697	CYP1A2 832

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=26 Page: 26.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=25 Page: 25.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=25 Page: 25.0	no
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=26 Page: 26.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=25 Page: 25.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=25 Page: 25.0	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=26 Page: 26.0	no
UGT 70	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=25 Page: 25.0	no
PXR 51	activator 342 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=25 Page: 25.0	yes [EC50 52.5 uM]
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=27 Page: 27.0	yes [IC50 1.86 uM]
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=5 Page: 5.0	yes [IC50 3.91 uM]
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=27 Page: 27.0	yes [IC50 4.02 uM]
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=27 Page: 27.0	yes [Inhibition 30 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=4 Page: 4.0	yes [Ki 0.6 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=4 Page: 4.0	yes [Ki 1.1 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A5 446	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=5 Page: 5.0	major
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=5 Page: 5.0	major	yes (co-administration study) Comment: Lapatinib exposure were reduced by 72% after CYP3A4 induction by carbamazepine, and increased to 3.6 times control after CYP3A4 inhibition by ketoconazole. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=5 Page: 5.0
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=5 Page: 5.0	minor
CYP2C8 810	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=5 Page: 5.0	minor	unknown (co-administration study) Comment: Based upon the ability of laptinib to act as a CYP 2C8 inhibitor in vitro, the Applicant agrees to perform an in vivo drug interaction study of the ability of steady-state lapatinib dosing to alter the pharmacokinetics of a single dose of paclitaxel or rosiglitazone. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=5 Page: 5.0
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=13 Page: 13.0	no
CYP2A6 626	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=13 Page: 13.0	no
CYP2B6 776	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=13 Page: 13.0	no
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=13 Page: 13.0	no
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=13 Page: 13.0	no
CYP2E1 729	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=13 Page: 13.0	no
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=26 Page: 26.0	yes
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=5 Page: 5.0	yes	unknown (co-administration study) Comment: Based upon the ability of laptinib to act as a Pgp inhibitor in vitro, the Applicant agrees to perform an in vivo drug interaction study of the ability of steady-state lapatinib dosing to alter the pharmacokinetics of a single dose of digoxin Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=5 Page: 5.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.ema.europa.eu/documents/assessment-report/tyverb-epar-public-assessment-report_en.pdf Page: -

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:49603	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:49603
ChemicalBook	CB8855402	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8855402
eMolecules	6757269	https://www.emolecules.com/cgi-bin/more?vid=6757269
MolPort	MolPort-006-069-221	https://www.molport.com/shop/molecule-link/MolPort-006-069-221
Selleck Chemicals	lapatinib	http://www.selleckchem.com/products/lapatinib.html
ZINC	ZINC000001550477	http://zinc15.docking.org/substances/ZINC000001550477

PubMed

Title	Date	PubMed
Recent advances in the treatment of salivary gland cancers: emphasis on molecular targeted therapy.	2007-09	17350323
Trastuzumab: mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancer.	2007-06	17229773
Combination treatment with Grb7 peptide and Doxorubicin or Trastuzumab (Herceptin) results in cooperative cell growth inhibition in breast cancer cells.	2007-05-21	17426702
Lapatinib plus capecitabine in breast cancer.	2007-04-05	17409332
relocating job wise? A mathematical model separates quantitatively the cytostatic and cytotoxic effects of a HER2 tyrosine kinase inhibitor.	2007-04-03	17407594
Chemotherapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials.	2007-03-26	17325704
Vinorelbine plus 3-weekly trastuzumab in metastatic breast cancer: a single-centre phase 2 trial.	2007-03-20	17374151
Gateways to clinical trials.	2007-03-09	17344945
Lapatinib moves forward in inflammatory and early HER2-positive breast cancer trials.	2007-03-07	17341725
Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity.	2007-03	17349580
The EGF receptor Hokey-Cokey.	2007-03	17349577
Targeting EGF-receptor-signalling in squamous cell carcinomas of the head and neck.	2007-02-12	17224925
Lapatinib antitumor activity is not dependent upon phosphatase and tensin homologue deleted on chromosome 10 in ErbB2-overexpressing breast cancers.	2007-02-01	17283152
TEACH: Tykerb evaluation after chemotherapy.	2007-02	17386127
Combined treatment of bladder cancer cell lines with lapatinib and varying chemotherapy regimens--evidence of schedule-dependent synergy.	2007-02	17320695
Lapatinib induces apoptosis in trastuzumab-resistant breast cancer cells: effects on insulin-like growth factor I signaling.	2007-02	17308062
European Society for Medical Oncology 2006: meeting highlights on targeted therapies. Istanbul, Turkey, 29 September-3 October 2006.	2007-02	17250464
Lapatinib: a dual inhibitor of EGFR and HER2 tyrosine kinase activity.	2007-02	17250463
Recent advances in the therapy of renal cancer.	2007-02	17250461
Dual inhibition of ErbB1 (EGFR/HER1) and ErbB2 (HER2/neu).	2007-02	17208435
Synergistic inhibition of breast cancer cell lines with a dual inhibitor of EGFR-HER-2/neu and a Bcl-2 inhibitor.	2007-02	17203189
The 17q12-q21 amplicon: Her2 and topoisomerase-IIalpha and their importance to the biology of solid tumours.	2007-02	17113234
Small molecule tyrosine kinase inhibitors in the treatment of solid tumors: an update of recent developments.	2007-02	17103252
Proteomic identification of secreted proteins as surrogate markers for signal transduction inhibitor activity.	2007-01-29	17211472
Therapeutic advances in the treatment of brain metastases.	2007-01	17339829
Prospective study of positron emission tomography for evaluation of the activity of lapatinib, a dual inhibitor of the ErbB1 and ErbB2 tyrosine kinases, in patients with advanced tumors.	2007-01	17060407
HER-2-positive breast cancer: hope beyond trastuzumab.	2007	17402790
Targeted therapy of breast cancer.	2007	17348846
HER2 therapy. HER2 (ERBB2): functional diversity from structurally conserved building blocks.	2007	17274834
Targeted therapy for metastatic breast cancer.	2006-12-28	17192546
Lapatinib plus capecitabine for HER2-positive advanced breast cancer.	2006-12-28	17192538
A novel mutation in the tyrosine kinase domain of ERBB2 in hepatocellular carcinoma.	2006-12-06	17150109
The molecular biology and immunology of glioblastoma multiforme (GBM) with the presentation of an immunotherapy protocol for a clinical trial.	2006-12	17278710
Targeting growth factor and antiangiogenic pathways in clear-cell renal cell carcinoma: rationale and ongoing trials.	2006-12	17239282
Gateways to clinical trials.	2006-12	17235418
Lapatinib: current status and future directions in breast cancer.	2006-11-18	17110623
Closing in on a cure.	2006-10-23	17432437
Receptor tyrosine kinase (RTK) inhibition is effective in chemosensitising EGFR-expressing drug resistant human ovarian cancer cell lines when used in combination with cytotoxic agents.	2006-10-16	16934227
Delivery of a healthy baby after first-trimester maternal exposure to lapatinib.	2006-10	17092403
[Molecular diagnostic and targeted therapy--"Barking dogs are going to bite": presentations from the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta 2006].	2006-10	17001557
Combination therapy with aromatase inhibitors: the next era of breast cancer treatment?	2006-09-18	16926831
Three new drugs available to fight kidney cancer.	2006-09-06	16954469
Identification of potentially useful combinations of epidermal growth factor receptor tyrosine kinase antagonists with conventional cytotoxic agents using median effect analysis.	2006-09	16940802
Emerging drugs to replace current leaders in first-line therapy for breast cancer.	2006-09	16939387
Two targets, one drug for new EGFR inhibitors.	2006-08-16	16912259
New hope for RCC patients.	2006-08	16998955
Lapatinib: a novel EGFR/HER2 tyrosine kinase inhibitor for cancer.	2006-07	16894399
Targeting the EGFR pathway for cancer therapy.	2006	17168718
Dual/pan-HER tyrosine kinase inhibitors: focus in breast cancer.	2006	17163175
HER2 therapy: molecular mechanisms of trastuzumab resistance.	2006	17096862

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dosage of TYKERB for advanced or metastatic breast cancer is 1,250 mg (5 tablets) given orally once daily on Days 1-21 continuously in combination with capecitabine 2,000 mg/m2 /day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle. The recommended dose of TYKERB for hormone receptor positive, HER2 positive metastatic breast cancer is 1500 mg (6 tablets) given orally once daily continuously in combination with letrozole. When TYKERB is coadministered with letrozole, the recommended dose of letrozole is 2.5 mg once daily. • TYKERB should be taken at least one hour before or one hour after a meal. However, capecitabine should be taken with food or within 30 minutes after food. • TYKERB should be taken once daily. Do not divide daily doses of TYKERB. • Modify dose for cardiac and other toxicities, severe hepatic impairment, and CYP3A4 drug interactions.

Route of Administration: Oral

In Vitro Use Guide

lapatinib-induced time- and dose-dependent phosphorylation dynamics in SKBR3 breast cancer cells. Among 4953 identified phosphopeptides from 1548 proteins, a small proportion (5-7%) was regulated at least twofold by 1-10 μm lapatinib.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:27:07 GMT 2025` Edited by `admin` on `Mon Mar 31 18:27:07 GMT 2025`
Record UNII	0VUA21238F
Record Status	`Validated (UNII)`
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Name

Type

Language

GSK-572016

Preferred Name

English

Lapatinib

Official Name

English

LAPATINIB [EMA EPAR]

Common Name

English

lapatinib [INN]

Common Name

English

GW-572016X

Code

English

LAPATINIB [MI]

Common Name

English

GW572016

Code

English

LAPATINIB [VANDF]

Common Name

English

GW-572016

Code

English

Lapatinib [WHO-DD]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175605