LAPATINIB DITOSYLATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C29H26ClFN4O4S.2C7H8O3S.H2O
Molecular Weight	943.476
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.CC1=CC=C(C=C1)S(O)(=O)=O.CC2=CC=C(C=C2)S(O)(=O)=O.CS(=O)(=O)CCNCC3=CC=C(O3)C4=CC=C5N=CN=C(NC6=CC=C(OCC7=CC=CC(F)=C7)C(Cl)=C6)C5=C4

InChI

InChIKey=XNRVGTHNYCNCFF-UHFFFAOYSA-N

InChI=1S/C29H26ClFN4O4S.2C7H8O3S.H2O/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;2*1-6-2-4-7(5-3-6)11(8,9)10;/h2-10,13-15,18,32H,11-12,16-17H2,1H3,(H,33,34,35);2*2-5H,1H3,(H,8,9,10);1H2

HIDE SMILES / InChI

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 58 Target ID: CHEMBL203 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022059s007lbl.pdf	Inhibitor 8297		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 8297		13.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Breast cancer 434 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022059s007lbl.pdf	Primary		Approved 8429	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 Co-administed with:: whole brain radiotherapy Sources: https://pubmed.ncbi.nlm.nih.gov/24197661	unhealthy, 50 years (range: 30–78 years) n = 27 Health Status: unhealthy Condition: (HER2)-positive breast cancer Age Group: 50 years (range: 30–78 years) Sex: F Population Size: 27 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 Co-administed with:: whole brain radiotherapy Sources: https://pubmed.ncbi.nlm.nih.gov/24197661	unhealthy, 50 years (range: 30–78 years) n = 5 Health Status: unhealthy Condition: (HER2)-positive breast cancer Age Group: 50 years (range: 30–78 years) Sex: F Population Size: 5 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 Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022059lbl.pdf	unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer \| estrogen receptor+ \|progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 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) n = 6 Health Status: unhealthy Condition: Solid Tumors Age Group: 60 years (range: 37 – 73 years) Sex: M+F Population Size: 6 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 Co-administed with:: Letrozole(2.5 mg/day) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022059lbl.pdf	unhealthy, 63 years n = 111 Health Status: unhealthy Condition: stage IV breast cancer \| estrogen receptor+ \|progesterone receptor+ Age Group: 63 years Sex: F Population Size: 111 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 1587 substrate 1737 inducer 781	substrate 1037 inhibitor 1767 inducer 389	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 911 P-gp 1461 CYP1A2 1524 CYP2C19 1478 UGT 35 BCRP 699 OATP1B1 788 OAT3 642	P-gp 1537 CYP3A5 395 CYP2C8 693 CYP2C19 991 CYP1A2 1054 CYP2B6 664 CYP2A6 543 CYP2E1 667 BCRP 561	CYP1A2 701

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=26 Page: 26.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=25 Page: 25.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=25 Page: 25.0	no
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=26 Page: 26.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=25 Page: 25.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=25 Page: 25.0	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=26 Page: 26.0	no
UGT 59	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=25 Page: 25.0	no
PXR 46	activator 214 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=25 Page: 25.0	yes [EC50 52.5 uM]
BCRP 773	inhibitor 3277 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 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=5 Page: 5.0	yes [IC50 3.91 uM]
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=27 Page: 27.0	yes [IC50 4.02 uM]
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=27 Page: 27.0	yes [Inhibition 30 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=4 Page: 4.0	yes [Ki 0.6 uM]
CYP3A4 1925	inhibitor 3277 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 395	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=5 Page: 5.0	major
CYP3A4 1737	substrate 3367 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 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=5 Page: 5.0	minor
CYP2C8 693	substrate 3367 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 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=13 Page: 13.0	no
CYP2A6 543	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=13 Page: 13.0	no
CYP2B6 664	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=13 Page: 13.0	no
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=13 Page: 13.0	no
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=13 Page: 13.0	no
CYP2E1 667	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=13 Page: 13.0	no
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022059s000_ClinPharmR.pdf#page=26 Page: 26.0	yes
P-gp 1537	substrate 3367 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 1647	inhibitor 1626 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
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
eMolecules	6757269	https://www.emolecules.com/cgi-bin/more?vid=6757269

PubMed

Title	Date	PubMed
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
New hope for RCC patients.	2006 Aug	16998955
Two targets, one drug for new EGFR inhibitors.	2006 Aug 16	16912259
The molecular biology and immunology of glioblastoma multiforme (GBM) with the presentation of an immunotherapy protocol for a clinical trial.	2006 Dec	17278710
Targeting growth factor and antiangiogenic pathways in clear-cell renal cell carcinoma: rationale and ongoing trials.	2006 Dec	17239282
Gateways to clinical trials.	2006 Dec	17235418
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 EGFR/HER2 tyrosine kinase inhibitor for cancer.	2006 Jul	16894399
Lapatinib: current status and future directions in breast cancer.	2006 Nov-Dec	17110623
Delivery of a healthy baby after first-trimester maternal exposure to lapatinib.	2006 Oct	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 Oct	17001557
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 Oct 16	16934227
Closing in on a cure.	2006 Oct 23	17432437
Identification of potentially useful combinations of epidermal growth factor receptor tyrosine kinase antagonists with conventional cytotoxic agents using median effect analysis.	2006 Sep	16940802
Emerging drugs to replace current leaders in first-line therapy for breast cancer.	2006 Sep	16939387
Combination therapy with aromatase inhibitors: the next era of breast cancer treatment?	2006 Sep 18	16926831
Three new drugs available to fight kidney cancer.	2006 Sep 6	16954469
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
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
TEACH: Tykerb evaluation after chemotherapy.	2007 Feb	17386127
Combined treatment of bladder cancer cell lines with lapatinib and varying chemotherapy regimens--evidence of schedule-dependent synergy.	2007 Feb	17320695
Lapatinib induces apoptosis in trastuzumab-resistant breast cancer cells: effects on insulin-like growth factor I signaling.	2007 Feb	17308062
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
Recent advances in the therapy of renal cancer.	2007 Feb	17250461
Dual inhibition of ErbB1 (EGFR/HER1) and ErbB2 (HER2/neu).	2007 Feb	17208435
Synergistic inhibition of breast cancer cell lines with a dual inhibitor of EGFR-HER-2/neu and a Bcl-2 inhibitor.	2007 Feb	17203189
The 17q12-q21 amplicon: Her2 and topoisomerase-IIalpha and their importance to the biology of solid tumours.	2007 Feb	17113234
Small molecule tyrosine kinase inhibitors in the treatment of solid tumors: an update of recent developments.	2007 Feb	17103252
Lapatinib antitumor activity is not dependent upon phosphatase and tensin homologue deleted on chromosome 10 in ErbB2-overexpressing breast cancers.	2007 Feb 1	17283152
Targeting EGF-receptor-signalling in squamous cell carcinomas of the head and neck.	2007 Feb 12	17224925
Therapeutic advances in the treatment of brain metastases.	2007 Jan	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 Jan	17060407
Proteomic identification of secreted proteins as surrogate markers for signal transduction inhibitor activity.	2007 Jan 29	17211472
Gateways to clinical trials.	2007 Jan-Feb	17344945
Trastuzumab: mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancer.	2007 Jun	17229773
Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity.	2007 Mar	17349580
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
Chemotherapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials.	2007 Mar 26	17325704
Lapatinib moves forward in inflammatory and early HER2-positive breast cancer trials.	2007 Mar 7	17341725
Combination treatment with Grb7 peptide and Doxorubicin or Trastuzumab (Herceptin) results in cooperative cell growth inhibition in breast cancer cells.	2007 May 21	17426702
Recent advances in the treatment of salivary gland cancers: emphasis on molecular targeted therapy.	2007 Sep	17350323

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.

Name

Type

Language

LAPATINIB DITOSYLATE

Official Name

English

LAPATINIB DITOLUENESULFONATE MONOHYDRATE

Common Name

English

LAPATINIB TOSILATE HYDRATE

Common Name

English

LAPATINIB DITOSYLATE MONOHYDRATE

Common Name

English

LAPATINIB DITOSYLATE [ORANGE BOOK]

Common Name

English

LAPATINIB TOSILATE HYDRATE [JAN]

Common Name

English

TYVERB

Brand Name

English

GW-572016F

Code

English

Lapatinib ditosylate monohydrate [WHO-DD]

Common Name

English

LAPATINIB DITOLUENESULFONATE MONOHYDRATE [MI]

Common Name

English

4-QUINAZOLINAMINE, N-(3-CHLORO-4-((3-FLUOROPHENYL)METHOXY)PHENYL)-6-(5-(((2-(METHYLSULPHONYL)ETHYL)AMINO)METHYL)-2-FURANYL)-, BIS(4-METHYLBENZENESULPHONATE), MONOHYDRATE

Common Name

English

LAPATINIB TOSILATE [MART.]

Common Name

English

LAPATINIB DITOSYLATE [USAN]

Common Name

English

GW572016F

Code

English

4-QUINAZOLINAMINE, N-(3-CHLORO-4-((3-FLUOROPHENYL)METHOXY)PHENYL)-6-(5-(((2-(METHYLSULFONYL)ETHYL)AMINO)METHYL)-2-FURANYL)-, 4-METHYLBENZENESULFONATE, HYDRATE (1:2:1)

Common Name

English

TYKERB

Brand Name

English

N-[3-Chloro-4-[(3-fluorobenzyl)oxy]phenyl]-6-[5-[[[2-(methylsulfonyl)ethyl]amino]methyl]furan-2-yl]quinazolin-4-amine bis(4-methylbenzenesulfonate) monohydrate

Common Name

English

4-QUINAZOLINAMINE, N-(3-CHLORO-4-((3-FLUOROPHENYL)METHOXY)PHENYL)-6-(5-(((2-(METHYLSULFONYL)ETHYL)AMINO)METHYL)-2-FURANYL)-, BIS(4-METHYLBENZENESULFONATE), MONOHYDRATE

Common Name

English

TYCERB

Brand Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2167