DGIdb - LAPATINIB Drug Record

LAPATINIB chembl:CHEMBL554 ApprovedAntineoplastic

Alternate Names:

TYVERB
GW-572016X
GSK-572016
LAPATINIB
GW-2016
GW-572016
GW572016
LAP016
N-{3-CHLORO-4-[(3-FLUOROBENZYL)OXY]PHENYL}-6-[5-({[2-(METHYLSULFONYL)ETHYL]AMINO}METHYL)-2-FURYL]-4-QUINAZOLINAMINE
GW 572016
FMM
N-{3-CHLORO-4-[(3-FLUOROPHENYL)METHOXY]PHENYL}-6-[5-({[2-(METHYLSULFONYL)ETHYL]AMINO}METHYL)-2-FURANYL]-4-QUINAZOLINAMINE
chembl:CHEMBL554
pubchem.compound:208908
chemidplus:231277-92-2
rxcui:480167
drugbank:01259

Drug Info:

FDA Approval	Breast cancer (HER2+)
Drug Class	Kinase Inhibitors
FDA Approval	approved
Drug Class	Small Molecule
Drug Indications	antineoplastic agent
Year of Approval	2007
Drug Class	antineoplastic agents, protein kinase inhibitors
Pharmaceutical Developer	GlaxoSmithKline
Source Reported Drug Name(s)	Lapatinib
Drug Class	EGFR inhibitor
Drug Categories	cytochrome p-450 cyp2c8 inhibitors (strength unknown)
Drug Categories	cytochrome p-450 cyp3a substrates
Drug Categories	cytochrome p-450 cyp3a4 inhibitors
Drug Categories	cytochrome p-450 cyp3a5 substrates
Drug Categories	cytochrome p-450 enzyme inhibitors
Drug Categories	cytochrome p-450 substrates
Drug Categories	hepatotoxic agents
Drug Categories	heterocyclic compounds, fused-ring
Drug Categories	kinase inhibitor
Drug Categories	p-glycoprotein inhibitors
Drug Categories	potential qtc-prolonging agents
Drug Categories	qtc prolonging agents
Drug Categories	quinazolines
Drug Categories	tyrosine kinase inhibitors

(16 More Sources)

Publications:

Chang et al., 2016, Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity., Nat. Biotechnol.
Lyu A et al., 2014, Design and synthesis of Lapatinib derivatives containing a branched side chain as HER1/HER2 targeting antitumor drug candidates., Eur J Med Chem
Geyer et al., 2006, Lapatinib plus capecitabine for HER2-positive advanced breast cancer., N. Engl. J. Med.
Wainberg et al., 2010, Lapatinib, a dual EGFR and HER2 kinase inhibitor, selectively inhibits HER2-amplified human gastric cancer cells and is synergistic with trastuzumab in vitro and in vivo., Clin. Cancer Res.
Xia et al., 2005, 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., Oncogene
Secrier et al., 2016, Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance., Nat. Genet.
Xia et al., 2002, Anti-tumor activity of GW572016: a dual tyrosine kinase inhibitor blocks EGF activation of EGFR/erbB2 and downstream Erk1/2 and AKT pathways., Oncogene
Ali et al., 2014, Response of an ERBB2-mutated inflammatory breast carcinoma to human epidermal growth factor receptor 2-targeted therapy., J. Clin. Oncol.
Baselga et al., 2012, Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial., Lancet
Tevaarwerk et al., 2009, Lapatinib: a small-molecule inhibitor of epidermal growth factor receptor and human epidermal growth factor receptor-2 tyrosine kinases used in the treatment of breast cancer., Clin Ther
Trowe et al., 2008, EXEL-7647 inhibits mutant forms of ErbB2 associated with lapatinib resistance and neoplastic transformation., Clin. Cancer Res.
Morrison Joly et al., 2016, Rictor/mTORC2 Drives Progression and Therapeutic Resistance of HER2-Amplified Breast Cancers., Cancer Res.
Clavarezza et al., 2016, Dual Block with Lapatinib and Trastuzumab Versus Single-Agent Trastuzumab Combined with Chemotherapy as Neoadjuvant Treatment of HER2-Positive Breast Cancer: A Meta-analysis of Randomized Trials., Clin. Cancer Res.
Wood et al., 2004, 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., Cancer Res.
Pan et al., 2015, Development and Characterization of Bladder Cancer Patient-Derived Xenografts for Molecularly Guided Targeted Therapy., PLoS ONE
Sartore-Bianchi et al., 2016, Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial., Lancet Oncol.
Greulich et al., 2012, Functional analysis of receptor tyrosine kinase mutations in lung cancer identifies oncogenic extracellular domain mutations of ERBB2., Proc. Natl. Acad. Sci. U.S.A.
de Martino et al., 2014, Impact of ERBB2 mutations on in vitro sensitivity of bladder cancer to lapatinib., Cancer Biol. Ther.
Grana et al., 2003, Epidermal growth factor receptor autocrine signaling in RIE-1 cells transformed by the Ras oncogene enhances radiation resistance., Cancer Res.
Bertotti et al., 2011, A molecularly annotated platform of patient-derived xenografts ("xenopatients") identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer., Cancer Discov
Kotschy et al., 2016, The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models., Nature
Leto et al., 2015, Sustained Inhibition of HER3 and EGFR Is Necessary to Induce Regression of HER2-Amplified Gastrointestinal Carcinomas., Clin. Cancer Res.
Cancer Cell Line Encyclopedia Consortium. et al., 2015, Pharmacogenomic agreement between two cancer cell line data sets., Nature
Scott et al., 1991, The effects of flosequinan on regional blood flow in normal man., Br J Clin Pharmacol
Kim et al., 2008, The growth inhibitory effect of lapatinib, a dual inhibitor of EGFR and HER2 tyrosine kinase, in gastric cancer cell lines., Cancer Lett.
Manole et al., 2016, JNK Pathway Activation Modulates Acquired Resistance to EGFR/HER2-Targeted Therapies., Cancer Res.
Sridhar J et al., 2014, Identification of quinones as HER2 inhibitors for the treatment of trastuzumab resistant breast cancer., Bioorg Med Chem Lett
Johnston et al., 2006, Lapatinib: a novel EGFR/HER2 tyrosine kinase inhibitor for cancer., Drugs Today
Biswas et al., 2016, Genomic profiling of multiple sequentially acquired tumor metastatic sites from an "exceptional responder" lung adenocarcinoma patient reveals extensive genomic heterogeneity and novel somatic variants driving treatment response., Cold Spring Harb Mol Case Stud
Rexer et al., 2013, Human breast cancer cells harboring a gatekeeper T798M mutation in HER2 overexpress EGFR ligands and are sensitive to dual inhibition of EGFR and HER2., Clin. Cancer Res.
Zhou et al., 2004, Effects of the EGFR/HER2 kinase inhibitor GW572016 on EGFR- and HER2-overexpressing breast cancer cell line proliferation, radiosensitization, and resistance., Int. J. Radiat. Oncol. Biol. Phys.
Wisinski et al., 2016, Phase I Study of an AKT Inhibitor (MK-2206) Combined with Lapatinib in Adult Solid Tumors Followed by Dose Expansion in Advanced HER2+ Breast Cancer., Clin. Cancer Res.
Hanker et al., 2013, Mutant PIK3CA accelerates HER2-driven transgenic mammary tumors and induces resistance to combinations of anti-HER2 therapies., Proc. Natl. Acad. Sci. U.S.A.
Leary et al., 2015, Antiproliferative Effect of Lapatinib in HER2-Positive and HER2-Negative/HER3-High Breast Cancer: Results of the Presurgical Randomized MAPLE Trial (CRUK E/06/039)., Clin. Cancer Res.
Satoh et al., 2014, Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: TyTAN--a randomized, phase III study., J. Clin. Oncol.
Guarneri et al., 2015, Prospective Biomarker Analysis of the Randomized CHER-LOB Study Evaluating the Dual Anti-HER2 Treatment With Trastuzumab and Lapatinib Plus Chemotherapy as Neoadjuvant Therapy for HER2-Positive Breast Cancer., Oncologist
Johnston et al., 2009, Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer., J. Clin. Oncol.
Lee et al., 2016, Serum Human Epidermal Growth Factor 2 Extracellular Domain as a Predictive Biomarker for Lapatinib Treatment Efficacy in Patients With Advanced Breast Cancer., J. Clin. Oncol.
Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.
Xia et al., 2004, Truncated ErbB2 receptor (p95ErbB2) is regulated by heregulin through heterodimer formation with ErbB3 yet remains sensitive to the dual EGFR/ErbB2 kinase inhibitor GW572016., Oncogene
Medina et al., 2008, Lapatinib: a dual inhibitor of human epidermal growth factor receptor tyrosine kinases., Clin Ther
Bachelot T et al., 2013, Lapatinib plus capecitabine in patients with previously untreated brain metastases from HER2-positive metastatic breast cancer (LANDSCAPE): a single-group phase 2 study., Lancet Oncol
MacConaill et al., 2014, Prospective enterprise-level molecular genotyping of a cohort of cancer patients., J Mol Diagn
Burris, 2004, Dual kinase inhibition in the treatment of breast cancer: initial experience with the EGFR/ErbB-2 inhibitor lapatinib., Oncologist
Kancha et al., 2011, Differential sensitivity of ERBB2 kinase domain mutations towards lapatinib., PLoS ONE
Lin NU et al., 2009, Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer., Clin Cancer Res
Bose et al., 2013, Activating HER2 mutations in HER2 gene amplification negative breast cancer., Cancer Discov
Boulbes et al., 2015, HER family kinase domain mutations promote tumor progression and can predict response to treatment in human breast cancer., Mol Oncol
Kwak et al., 2015, Molecular Heterogeneity and Receptor Coamplification Drive Resistance to Targeted Therapy in MET-Amplified Esophagogastric Cancer., Cancer Discov
Lee et al., 2006, Somatic mutations of ERBB2 kinase domain in gastric, colorectal, and breast carcinomas., Clin. Cancer Res.
Grellety et al., 2016, A clinical case of invasive lobular breast carcinoma with ERBB2 and CDH1 mutations presenting a dramatic response to anti-HER2-directed therapy., Ann. Oncol.
Witkiewicz et al., 2014, CDK4/6 inhibition provides a potent adjunct to Her2-targeted therapies in preclinical breast cancer models., Genes Cancer
Vazquez-Martin et al., 2011, Lapatinib, a dual HER1/HER2 tyrosine kinase inhibitor, augments basal cleavage of HER2 extracellular domain (ECD) to inhibit HER2-driven cancer cell growth., J. Cell. Physiol.
Guarneri et al., 2012, Preoperative chemotherapy plus trastuzumab, lapatinib, or both in human epidermal growth factor receptor 2-positive operable breast cancer: results of the randomized phase II CHER-LOB study., J. Clin. Oncol.
Zuo et al., 2016, Dual Characteristics of Novel HER2 Kinase Domain Mutations in Response to HER2-Targeted Therapies in Human Breast Cancer., Clin. Cancer Res.
Kavuri et al., 2015, HER2 activating mutations are targets for colorectal cancer treatment., Cancer Discov
Langer, 2004, Emerging role of epidermal growth factor receptor inhibition in therapy for advanced malignancy: focus on NSCLC., Int. J. Radiat. Oncol. Biol. Phys.
Li et al., 2014, Modulation of ErbB2 blockade in ErbB2-positive cancers: the role of ErbB2 Mutations and PHLDA1., PLoS ONE
Blackwell et al., 2010, Randomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer., J. Clin. Oncol.
Lorenzen et al., 2015, Lapatinib versus lapatinib plus capecitabine as second-line treatment in human epidermal growth factor receptor 2-amplified metastatic gastro-oesophageal cancer: a randomised phase II trial of the Arbeitsgemeinschaft Internistische Onkologie., Eur. J. Cancer
Hecht et al., 2016, Lapatinib in Combination With Capecitabine Plus Oxaliplatin in Human Epidermal Growth Factor Receptor 2-Positive Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Adenocarcinoma: TRIO-013/LOGiC--A Randomized Phase III Trial., J. Clin. Oncol.
Baselga et al., 2016, Relationship between Tumor Biomarkers and Efficacy in EMILIA, a Phase III Study of Trastuzumab Emtansine in HER2-Positive Metastatic Breast Cancer., Clin. Cancer Res.
Funke S et al., 2008, Pharmacogenetics in colorectal cancer: a systematic review., Pharmacogenomics
Herbst RS et al., 2004, Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2., J Clin Oncol
Bonner JA et al., 2006, Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck., N Engl J Med
Normanno N et al., 2006, Epidermal growth factor receptor (EGFR) signaling in cancer., Gene
Ross et al., 2010, Randomized phase II multicenter trial of two schedules of lapatinib as first- or second-line monotherapy in patients with advanced or metastatic non-small cell lung cancer., Clin. Cancer Res.
Giaccone G et al., 2004, Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 1., J Clin Oncol
Vermorken JB et al., 2008, Platinum-based chemotherapy plus cetuximab in head and neck cancer., N Engl J Med
Frattini et al., 2013, The integrated landscape of driver genomic alterations in glioblastoma., Nat. Genet.
Gilmer et al., 2008, Impact of common epidermal growth factor receptor and HER2 variants on receptor activity and inhibition by lapatinib., Cancer Res.
Thatcher N et al., 2005, Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer)., Lancet
Jonker et al., 2007, Cetuximab for the treatment of colorectal cancer., N. Engl. J. Med.
Rossi A et al., 2013, Should epidermal growth factor receptor tyrosine kinase inhibitors be considered ideal drugs for the treatment of selected advanced non-small cell lung cancer patients?, Cancer Treat Rev
Yang et al., 2001, Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy., Crit. Rev. Oncol. Hematol.
Li et al., 2008, BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models., Oncogene
Van Cutsem et al., 2009, Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer., N. Engl. J. Med.
Giusti RM et al., 2008, U.S. Food and Drug Administration approval: panitumumab for epidermal growth factor receptor-expressing metastatic colorectal carcinoma with progression following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens., Clin Cancer Res
Leslie et al., 2012, Lapatinib and potential prognostic value of EGFR mutations in a Gynecologic Oncology Group phase II trial of persistent or recurrent endometrial cancer., Gynecol. Oncol.
Jorissen RN et al., 2003, Epidermal growth factor receptor: mechanisms of activation and signalling., Exp Cell Res
Mayo C et al., 2012, Pharmacogenetics of EGFR in lung cancer: perspectives and clinical applications., Pharmacogenomics
Jaiswal et al., 2013, Oncogenic ERBB3 mutations in human cancers., Cancer Cell
Bidard FC et al., 2015, Response to dual HER2 blockade in a patient with HER3-mutant metastatic breast cancer., Ann Oncol
Canfield et al., 2015, Receptor tyrosine kinase ERBB4 mediates acquired resistance to ERBB2 inhibitors in breast cancer cells., Cell Cycle
Prickett et al., 2009, Analysis of the tyrosine kinome in melanoma reveals recurrent mutations in ERBB4., Nat. Genet.
Eichhorn PJ et al., 2008, Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235., Cancer Res
Loibl S et al., 2014, PIK3CA mutations are associated with lower rates of pathologic complete response to anti-human epidermal growth factor receptor 2 (her2) therapy in primary HER2-overexpressing breast cancer., J Clin Oncol
Dogruluk et al., 2015, Identification of Variant-Specific Functions of PIK3CA by Rapid Phenotyping of Rare Mutations., Cancer Res.
Davies et al., 2012, Preclinical pharmacology of AZD5363, an inhibitor of AKT: pharmacodynamics, antitumor activity, and correlation of monotherapy activity with genetic background., Mol. Cancer Ther.
Spraggs CF et al., 2013, Genetic characterization to improve interpretation and clinical management of hepatotoxicity caused by tyrosine kinase inhibitors., Pharmacogenomics
Barbara JE et al., 2013, Metabolism-dependent inhibition of CYP3A4 by lapatinib: evidence for formation of a metabolic intermediate complex with a nitroso/oxime metabolite formed via a nitrone intermediate., Drug Metab Dispos
Chan EC et al., 2012, Interaction of lapatinib with cytochrome P450 3A5., Drug Metab Dispos
Schaid DJ et al., 2014, Prospective validation of HLA-DRB1*07:01 allele carriage as a predictive risk factor for lapatinib-induced liver injury., J Clin Oncol
Spraggs CF et al., 2018, Characterisation of the HLA-DRB1*07:01 biomarker for lapatinib-induced liver toxicity during treatment of early-stage breast cancer patients with lapatinib in combination with trastuzumab and/or taxanes., Pharmacogenomics J
Spraggs CF et al., 2011, HLA-DQA1*02:01 is a major risk factor for lapatinib-induced hepatotoxicity in women with advanced breast cancer., J Clin Oncol
LaBonte et al., 2011, The dual EGFR/HER2 inhibitor lapatinib synergistically enhances the antitumor activity of the histone deacetylase inhibitor panobinostat in colorectal cancer models., Cancer Res.
Montero-Conde et al., 2013, Relief of feedback inhibition of HER3 transcription by RAF and MEK inhibitors attenuates their antitumor effects in BRAF-mutant thyroid carcinomas., Cancer Discov
Xia et al., 2006, Regulation of survivin by ErbB2 signaling: therapeutic implications for ErbB2-overexpressing breast cancers., Cancer Res.
Baumslag, Trace metal studies in Bushman hair., Arch. Environ. Health
Karajannis et al., 2012, Phase II trial of lapatinib in adult and pediatric patients with neurofibromatosis type 2 and progressive vestibular schwannomas., Neuro-oncology
Leung et al., 2015, Combining lapatinib and pertuzumab to overcome lapatinib resistance due to NRG1-mediated signalling in HER2-amplified breast cancer., Oncotarget
Wilson et al., 2011, Neuregulin-1-mediated autocrine signaling underlies sensitivity to HER2 kinase inhibitors in a subset of human cancers., Cancer Cell
Zhao et al., 2014, Mislocalization of p27 to the cytoplasm of breast cancer cells confers resistance to anti-HER2 targeted therapy., Oncotarget

LAPATINIB HLA-DQA1

Interaction Score: 2.03

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
24687830 21245432

Sources:
FDA PharmGKB
LAPATINIB EEF2K

Interaction Score: 2.03

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
TTD
LAPATINIB ERBB2

Interaction Score: 1.03

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

combination therapy Lapatinib;Chemotherapy

Drug family ERBB2 inhibitor;Chemotherapy

Alteration ERBB2:amp

PMIDs:
26619011 25305330 17192538 20179222 16091755 27595477 12214266 24516025 22257673 20110044 18413839 27197158 27140927 15374980 26270481 27108243 22908275 24971884 14633707 22586653 27760111 26296355 26570998 2015169 18774637 27450453 24355130 16894399 27900369 23948973 14751502 27026198 23940356 25398453 24868024 26245675 19786658 26811533 11752352 14737100 18803986 23122784 25157968 15163842 22046346 19228746 23220880 25435280 26432108 16397024 26487584 25221644 20658522 22493419 27697991 26243863 14967461 25238247 20124187 25694417 26628478 26920887

Sources:
ClearityFoundationBiomarkers TEND DTC OncoKB FDA PharmGKB DoCM JAX-CKB TdgClinicalTrial CIViC TTD DrugBank TALC MyCancerGenome GuideToPharmacology CGI
LAPATINIB CDH1

Interaction Score: 0.68

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Lapatinib + Capecitabine

Indication/Tumor Type breast cancer

Response Type sensitive

PMIDs:
26487584

Sources:
JAX-CKB
LAPATINIB EGFR

Interaction Score: 0.55

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Reported Cancer Type Prostate

Alteration EGFR:E690K

Drug family ERBB2 inhibitor

PMIDs:
25305330 18681783 27595477 12214266 14990633 16467544 16377102 20110044 20215545 14990632 18784101 23917401 15374980 14633707 18199554 16257339 24355130 16894399 18003960 14751502 23022519 11255078 18408761 19339720 11752352 18316547 14737100 18803986 22885469 15163842 12648464 20658522 14967461 22594511

Sources:
ClearityFoundationClinicalTrial CancerCommons TEND DTC OncoKB PharmGKB DoCM JAX-CKB TdgClinicalTrial CIViC TTD DrugBank TALC GuideToPharmacology CGI
LAPATINIB NF2

Interaction Score: 0.51

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family ERBB2 inhibitor

Alteration NF2:del

Alteration NF2:.

PMIDs:
973739 22844108

Sources:
CGI
LAPATINIB ERBB3

Interaction Score: 0.46

Interaction Types & Directionality:

n/a

Interaction Info:

Clinical Status preclinical

Pathway activation

Variant Effect gain-of-function

PMIDs:
23680147 25953157 25398453

Sources:
PharmGKB DoCM CIViC CGI
LAPATINIB ABCB11

Interaction Score: 0.41

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
23556451

Sources:
PharmGKB
LAPATINIB ERBB4

Interaction Score: 0.4

Interaction Types & Directionality:

n/a

Interaction Info:

Variant Effect gain-of-function

Pathway activation

Clinical Status preclinical

PMIDs:
25590338 19718025

Sources:
DTC PharmGKB DoCM JAX-CKB CIViC CGI
LAPATINIB CDKN1B

Interaction Score: 0.34

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
25587029

Sources:
CIViC
LAPATINIB NRG1

Interaction Score: 0.34

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family ERBB2 inhibitor

Alteration NRG1__.

PMIDs:
25691057 21840482

Sources:
CIViC CGI
LAPATINIB HLA-DRB1

Interaction Score: 0.26

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
24687830 28786423

Sources:
FDA PharmGKB
LAPATINIB PIK3CA

Interaction Score: 0.14

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type no benefit

Approval Status Preclinical - Pdx

Indication/Tumor Type urinary bladder cancer

PMIDs:
19010894 26270481 25199759 26627007 23940356 26245675 22294718 26920887

Sources:
PharmGKB JAX-CKB CIViC
LAPATINIB BIRC5

Interaction Score: 0.11

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
16452223

Sources:
NCI
LAPATINIB CCND1

Interaction Score: 0.1

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
PharmGKB
LAPATINIB FGFR2

Interaction Score: 0.07

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type sensitive

PMIDs:
27595477

Sources:
JAX-CKB
LAPATINIB MET

Interaction Score: 0.07

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family ERBB2 inhibitor

Alteration MET:amp;ERBB2:amp

combination therapy Crizotinib + Lapatinib

PMIDs:
27595477 26432108

Sources:
JAX-CKB CGI
LAPATINIB BRAF

Interaction Score: 0.06

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type sensitive

combination therapy Lapatinib + Panobinostat

Indication/Tumor Type colorectal cancer

PMIDs:
21464044 23365119

Sources:
JAX-CKB
LAPATINIB CYP3A5

Interaction Score: 0.06

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
23404373 22511346

Sources:
DTC
LAPATINIB PGR

Interaction Score: 0.06

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
FDA PharmGKB
LAPATINIB KRAS

Interaction Score: 0.04

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Trastuzumab;Lapatinib

Drug family ERBB2 mAb inhibitor;ERBB2 inhibitor

Alteration KRAS:.

PMIDs:
27108243

Sources:
JAX-CKB CGI
LAPATINIB SRC

Interaction Score: 0.04

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Indication/Tumor Type urinary bladder cancer

Response Type no benefit

PMIDs:
26270481

Sources:
JAX-CKB
LAPATINIB AURKB

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
LAPATINIB RET

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
LAPATINIB ESR2

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
PharmGKB
LAPATINIB ESR1

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
FDA PharmGKB
LAPATINIB YES1

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
LAPATINIB CYP3A4

Interaction Score: 0.0

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
22511346

Sources:
DTC

DrugBank: DB01259

Version: 5.1.7

Alternate Names:

231277-92-2 CAS Number

Tycerb Drug Brand

Tykerb Drug Brand

Drug Info:

Drug Type small molecule

Drug Groups approved

Drug Groups investigational

Publications:

Xia et al., 2002, Anti-tumor activity of GW572016: a dual tyrosine kinase inhibitor blocks EGF activation of EGFR/erbB2 and downstream Erk1/2 and AKT pathways., Oncogene

Tevaarwerk et al., 2009, Lapatinib: a small-molecule inhibitor of epidermal growth factor receptor and human epidermal growth factor receptor-2 tyrosine kinases used in the treatment of breast cancer., Clin Ther

Wood et al., 2004, 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., Cancer Res.

CancerCommons: LAPATINIB
- Version: 25-July-2013
Alternate Names:

208908 PubChem Drug ID

Drug Info:

Drug Class EGFR inhibitor

Source Reported Drug Name(s) Lapatinib

Pharmaceutical Developer GlaxoSmithKline

Publications:
MyCancerGenome: LAPATINIB
- Version: 20-Jun-2017
Alternate Names:

GSK572016 Development Name

GW2016 Development Name

TYKERB Trade Name

Drug Info:

Drug Class Kinase Inhibitors

FDA Approval Breast cancer (HER2+)

Publications:
TdgClinicalTrial: LAPATINIB
- Version: January-2014
Alternate Names:

Drug Info:

Drug Indications antineoplastic agent

Drug Class Small Molecule

FDA Approval approved

Publications:
TEND: LAPATINIB
- Version: 01-August-2011
Alternate Names:

Drug Info:

Drug Class antineoplastic agents, protein kinase inhibitors

Year of Approval 2007

Publications:
NCI: GW572016
- Version: 14-September-2017
Alternate Names:

C26653 NCI drug code

Drug Info:

Publications:

Xia et al., 2006, Regulation of survivin by ErbB2 signaling: therapeutic implications for ErbB2-overexpressing breast cancers., Cancer Res.

DTC: LAPATINIB

Version: 02-September-2020

Alternate Names:

CHEMBL554 ChEMBL Drug ID

Drug Info:

Publications:

Barbara JE et al., 2013, Metabolism-dependent inhibition of CYP3A4 by lapatinib: evidence for formation of a metabolic intermediate complex with a nitroso/oxime metabolite formed via a nitrone intermediate., Drug Metab Dispos

Chan EC et al., 2012, Interaction of lapatinib with cytochrome P450 3A5., Drug Metab Dispos

Lyu A et al., 2014, Design and synthesis of Lapatinib derivatives containing a branched side chain as HER1/HER2 targeting antitumor drug candidates., Eur J Med Chem

PharmGKB: lapatinib

Version: 18-August-2020

Alternate Names:

Drug Info:

Publications:

Schaid DJ et al., 2014, Prospective validation of HLA-DRB107:01 allele carriage as a predictive risk factor for lapatinib-induced liver injury., J Clin Oncol

Spraggs CF et al., 2018, Characterisation of the HLA-DRB107:01 biomarker for lapatinib-induced liver toxicity during treatment of early-stage breast cancer patients with lapatinib in combination with trastuzumab and/or taxanes., Pharmacogenomics J

Cancer Cell Line Encyclopedia Consortium. et al., 2015, Pharmacogenomic agreement between two cancer cell line data sets., Nature

CGI: Lapatinib

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Scott et al., 1991, The effects of flosequinan on regional blood flow in normal man., Br J Clin Pharmacol

Lorenzen et al., 2015, Lapatinib versus lapatinib plus capecitabine as second-line treatment in human epidermal growth factor receptor 2-amplified metastatic gastro-oesophageal cancer: a randomised phase II trial of the Arbeitsgemeinschaft Internistische Onkologie., Eur. J. Cancer

Baumslag, Trace metal studies in Bushman hair., Arch. Environ. Health

JAX-CKB: Lapatinib

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Pan et al., 2015, Development and Characterization of Bladder Cancer Patient-Derived Xenografts for Molecularly Guided Targeted Therapy., PLoS ONE

Secrier et al., 2016, Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance., Nat. Genet.

Kwak et al., 2015, Molecular Heterogeneity and Receptor Coamplification Drive Resistance to Targeted Therapy in MET-Amplified Esophagogastric Cancer., Cancer Discov

DoCM: LAPATINIB

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Prickett et al., 2009, Analysis of the tyrosine kinome in melanoma reveals recurrent mutations in ERBB4., Nat. Genet.

Leslie et al., 2012, Lapatinib and potential prognostic value of EGFR mutations in a Gynecologic Oncology Group phase II trial of persistent or recurrent endometrial cancer., Gynecol. Oncol.

Jaiswal et al., 2013, Oncogenic ERBB3 mutations in human cancers., Cancer Cell

CIViC: LAPATINIB

Version: 14-September-2020

Alternate Names:

Drug Info:

Publications:

Li et al., 2008, BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models., Oncogene

Geyer et al., 2006, Lapatinib plus capecitabine for HER2-positive advanced breast cancer., N. Engl. J. Med.

Xia et al., 2005, 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., Oncogene

TTD: Lapatinib
- Version: 2020.06.01
Alternate Names:

D08CDI TTD Drug ID

Drug Info:

Publications:
TALC: LAPATINIB
- Version: 12-May-2016
Alternate Names:

TYKERB Drug Trade Name

Drug Info:

Publications:
ChemblDrugs: chembl:CHEMBL554
- Version: ChEMBL_27
Alternate Names:

Drug Info:

Publications:
ClearityFoundationBiomarkers: LAPATINIB
- Version: 26-July-2013
Alternate Names:

Drug Info:

Publications:
ClearityFoundationClinicalTrial: LAPATINIB
- Version: 15-June-2013
Alternate Names:

Drug Info:

Publications:
OncoKB: Lapatinib
- Version: 23-July-2020
Alternate Names:

Drug Info:

Publications:
FDA: Lapatinib
- Version: 04-September-2020
Alternate Names:

Drug Info:

Publications:
GuideToPharmacology: 178102319
- Version: 29-September-2020
Alternate Names:

Drug Info:

Publications:

combination therapy	Lapatinib;Chemotherapy
Drug family	ERBB2 inhibitor;Chemotherapy
Alteration	ERBB2:amp

combination therapy	Lapatinib + Capecitabine
Indication/Tumor Type	breast cancer
Response Type	sensitive

Reported Cancer Type	Prostate
Alteration	EGFR:E690K
Drug family	ERBB2 inhibitor

Clinical Status	preclinical
Pathway	activation
Variant Effect	gain-of-function

Response Type	no benefit
Approval Status	Preclinical - Pdx
Indication/Tumor Type	urinary bladder cancer

Evidence Type	Actionable
Approval Status	Preclinical - Cell culture
Response Type	sensitive

combination therapy	Trastuzumab;Lapatinib
Drug family	ERBB2 mAb inhibitor;ERBB2 inhibitor
Alteration	KRAS:.

Drug Type	small molecule
Drug Groups	approved
Drug Groups	investigational

GSK572016	Development Name
GW2016	Development Name
TYKERB	Trade Name

antagonist (inhibitory)
inhibitor (inhibitory)

antagonist (inhibitory)
inhibitor (inhibitory)

LAPATINIB Drug Record

LAPATINIB chembl:CHEMBL554 ApprovedAntineoplastic

Alternate Names:

Drug Info:

Publications:

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 24687830 21245432

Sources: FDA PharmGKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: None found

Sources: TTD

Interaction Types & Directionality: antagonist (inhibitory) inhibitor (inhibitory)

Interaction Info: combination therapy Lapatinib;Chemotherapy Drug family ERBB2 inhibitor;Chemotherapy Alteration ERBB2:amp

Sources: ClearityFoundationBiomarkers TEND DTC OncoKB FDA PharmGKB DoCM JAX-CKB TdgClinicalTrial CIViC TTD DrugBank TALC MyCancerGenome GuideToPharmacology CGI

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Lapatinib + Capecitabine Indication/Tumor Type breast cancer Response Type sensitive

PMIDs: 26487584

Sources: JAX-CKB

Interaction Types & Directionality: antagonist (inhibitory) inhibitor (inhibitory)

Interaction Info: Reported Cancer Type Prostate Alteration EGFR:E690K Drug family ERBB2 inhibitor

Sources: ClearityFoundationClinicalTrial CancerCommons TEND DTC OncoKB PharmGKB DoCM JAX-CKB TdgClinicalTrial CIViC TTD DrugBank TALC GuideToPharmacology CGI

Interaction Types & Directionality: n/a

Interaction Info: Drug family ERBB2 inhibitor Alteration NF2:del Alteration NF2:.

PMIDs: 973739 22844108

Sources: CGI

Interaction Types & Directionality: n/a

Interaction Info: Clinical Status preclinical Pathway activation Variant Effect gain-of-function

PMIDs: 23680147 25953157 25398453

Sources: PharmGKB DoCM CIViC CGI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 23556451

Sources: PharmGKB

Interaction Types & Directionality: n/a

Interaction Info: Variant Effect gain-of-function Pathway activation Clinical Status preclinical

PMIDs: 25590338 19718025

Sources: DTC PharmGKB DoCM JAX-CKB CIViC CGI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 25587029

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info: Drug family ERBB2 inhibitor Alteration NRG1__.

PMIDs: 25691057 21840482

Sources: CIViC CGI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 24687830 28786423

Sources: FDA PharmGKB

Interaction Types & Directionality: n/a

Interaction Info: Response Type no benefit Approval Status Preclinical - Pdx Indication/Tumor Type urinary bladder cancer

PMIDs: 19010894 26270481 25199759 26627007 23940356 26245675 22294718 26920887

Sources: PharmGKB JAX-CKB CIViC

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 16452223

Sources: NCI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: None found

Sources: PharmGKB

Interaction Types & Directionality: n/a

Interaction Info: Evidence Type Actionable Approval Status Preclinical - Cell culture Response Type sensitive

PMIDs: 27595477

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info: Drug family ERBB2 inhibitor Alteration MET:amp;ERBB2:amp combination therapy Crizotinib + Lapatinib

PMIDs: 27595477 26432108

Sources: JAX-CKB CGI

Interaction Types & Directionality: n/a

Interaction Info: Response Type sensitive combination therapy Lapatinib + Panobinostat Indication/Tumor Type colorectal cancer

PMIDs: 21464044 23365119

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 23404373 22511346

Sources: DTC

Interaction Types & Directionality: n/a

Interaction Types & Directionality:

n/a

PMIDs:
24687830 21245432

Sources:
FDA PharmGKB

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
TTD

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

combination therapy Lapatinib;Chemotherapy

Drug family ERBB2 inhibitor;Chemotherapy

Alteration ERBB2:amp

Sources:
ClearityFoundationBiomarkers TEND DTC OncoKB FDA PharmGKB DoCM JAX-CKB TdgClinicalTrial CIViC TTD DrugBank TALC MyCancerGenome GuideToPharmacology CGI

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Lapatinib + Capecitabine

Indication/Tumor Type breast cancer

Response Type sensitive

PMIDs:
26487584

Sources:
JAX-CKB

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Reported Cancer Type Prostate

Alteration EGFR:E690K

Drug family ERBB2 inhibitor

Sources:
ClearityFoundationClinicalTrial CancerCommons TEND DTC OncoKB PharmGKB DoCM JAX-CKB TdgClinicalTrial CIViC TTD DrugBank TALC GuideToPharmacology CGI

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family ERBB2 inhibitor

Alteration NF2:del

Alteration NF2:.

PMIDs:
973739 22844108

Sources:
CGI

Interaction Types & Directionality:

n/a

Interaction Info:

Clinical Status preclinical

Pathway activation

Variant Effect gain-of-function

PMIDs:
23680147 25953157 25398453

Sources:
PharmGKB DoCM CIViC CGI

Interaction Types & Directionality:

n/a

PMIDs:
23556451

Sources:
PharmGKB

Interaction Types & Directionality:

n/a

Interaction Info:

Variant Effect gain-of-function

Pathway activation

Clinical Status preclinical

PMIDs:
25590338 19718025

Sources:
DTC PharmGKB DoCM JAX-CKB CIViC CGI

Interaction Types & Directionality:

n/a

PMIDs:
25587029

Sources:
CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family ERBB2 inhibitor

Alteration NRG1__.

PMIDs:
25691057 21840482

Sources:
CIViC CGI

Interaction Types & Directionality:

n/a

PMIDs:
24687830 28786423

Sources:
FDA PharmGKB

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type no benefit

Approval Status Preclinical - Pdx

Indication/Tumor Type urinary bladder cancer

PMIDs:
19010894 26270481 25199759 26627007 23940356 26245675 22294718 26920887

Sources:
PharmGKB JAX-CKB CIViC

Interaction Types & Directionality:

n/a

PMIDs:
16452223

Sources:
NCI

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
PharmGKB

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type sensitive

PMIDs:
27595477

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family ERBB2 inhibitor

Alteration MET:amp;ERBB2:amp

combination therapy Crizotinib + Lapatinib

PMIDs:
27595477 26432108

Sources:
JAX-CKB CGI

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type sensitive

combination therapy Lapatinib + Panobinostat

Indication/Tumor Type colorectal cancer

PMIDs:
21464044 23365119

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

PMIDs:
23404373 22511346

Sources:
DTC

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
FDA PharmGKB

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Trastuzumab;Lapatinib

Drug family ERBB2 mAb inhibitor;ERBB2 inhibitor

Alteration KRAS:.

PMIDs:
27108243

Sources:
JAX-CKB CGI

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Indication/Tumor Type urinary bladder cancer

Response Type no benefit

PMIDs:
26270481

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
DTC