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
Targeting HER2 in brain metastases from breast cancer.	2003 Nov 15	14654521
Gateways to clinical trials.	2003 Oct	14671684
Gateways to clinical trials.	2004 Jan-Feb	14988742
Early success of combined EGFR and Her2 receptor blockade as a clinical strategy in breast cancer.	2004 Jun	15717407
Gateways to clinical trials.	2004 Nov	15632957
A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells.	2004 Sep 15	15374980
Study of the biologic effects of lapatinib, a reversible inhibitor of ErbB1 and ErbB2 tyrosine kinases, on tumor growth and survival pathways in patients with advanced malignancies.	2005 Apr 10	15684311
The epidermal growth factor receptor as a target for colorectal cancer therapy.	2005 Feb	15726506
Phase I pharmacokinetic studies evaluating single and multiple doses of oral GW572016, a dual EGFR-ErbB2 inhibitor, in healthy subjects.	2005 Jan	15528979
The dual ErbB1/ErbB2 inhibitor, lapatinib (GW572016), cooperates with tamoxifen to inhibit both cell proliferation- and estrogen-dependent gene expression in antiestrogen-resistant breast cancer.	2005 Jan 1	15665275
Gateways to clinical trials.	2005 Jan-Feb	15834459
Clinical trials of intracellular signal transductions inhibitors for breast cancer--a strategy to overcome endocrine resistance.	2005 Jul	16113091
Gateways to clinical trials.	2005 Jun	16082422
Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain.	2005 Mar	15737014
EGFR inhibition in non-small cell lung cancer: resistance, once again, rears its ugly head.	2005 Mar	15736989
Combining lapatinib (GW572016), a small molecule inhibitor of ErbB1 and ErbB2 tyrosine kinases, with therapeutic anti-ErbB2 antibodies enhances apoptosis of ErbB2-overexpressing breast cancer cells.	2005 Sep 15	16091755
Antitumor activity of HER-2 inhibitors.	2005 Sep 8	16051028
Targeting the EGFR pathway for cancer therapy.	2006	17168718
Dual/pan-HER tyrosine kinase inhibitors: focus in breast cancer.	2006	17163175
Lessons from the drug discovery of lapatinib, a dual ErbB1/2 tyrosine kinase inhibitor.	2006	16719802
Targeted therapy for metastatic breast cancer.	2006 Dec 28	17192546
Lapatinib plus capecitabine for HER2-positive advanced breast cancer.	2006 Dec 28	17192538
A novel mutation in the tyrosine kinase domain of ERBB2 in hepatocellular carcinoma.	2006 Dec 6	17150109
Lapatinib: a novel dual tyrosine kinase inhibitor with activity in solid tumors.	2006 Feb	16418322
Regulation of survivin by ErbB2 signaling: therapeutic implications for ErbB2-overexpressing breast cancers.	2006 Feb 1	16452223
Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells.	2006 Feb 1	16452222
HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors.	2006 Jul	16843263
Old and new perspectives in the pharmacological treatment of advanced or recurrent endometrial cancer: Hormonal therapy, chemotherapy and molecularly targeted therapies.	2006 Jun	16436330
Gateways to clinical trials.	2006 Mar	16636723
Her-2 targeted therapy: beyond breast cancer and trastuzumab.	2006 Mar	16507217
A phase II study of vinflunine in bladder cancer patients progressing after first-line platinum-containing regimen.	2006 May 22	16622447
Closing in on a cure.	2006 Oct 23	17432437
Targeted therapy of breast cancer.	2007	17348846
HER2 therapy. HER2 (ERBB2): functional diversity from structurally conserved building blocks.	2007	17274834
relocating job wise? A mathematical model separates quantitatively the cytostatic and cytotoxic effects of a HER2 tyrosine kinase inhibitor.	2007 Apr 3	17407594
Lapatinib plus capecitabine in breast cancer.	2007 Apr 5	17409332
European Society for Medical Oncology 2006: meeting highlights on targeted therapies. Istanbul, Turkey, 29 September-3 October 2006.	2007 Feb	17250464
Lapatinib: a dual inhibitor of EGFR and HER2 tyrosine kinase activity.	2007 Feb	17250463
Dual inhibition of ErbB1 (EGFR/HER1) and ErbB2 (HER2/neu).	2007 Feb	17208435
The 17q12-q21 amplicon: Her2 and topoisomerase-IIalpha and their importance to the biology of solid tumours.	2007 Feb	17113234
The EGF receptor Hokey-Cokey.	2007 Mar	17349577
Vinorelbine plus 3-weekly trastuzumab in metastatic breast cancer: a single-centre phase 2 trial.	2007 Mar 20	17374151
Combination treatment with Grb7 peptide and Doxorubicin or Trastuzumab (Herceptin) results in cooperative cell growth inhibition in breast cancer cells.	2007 May 21	17426702

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