Drug Details

General Information of the Drug (ID: DR6077)
Name
Lapatinib
Synonyms
FMM; Tycerb; Lapatinib Ditosylate; Lapatinib [INN]; Lapatinib tosilate hydrate; GSK 572016; GSK572016; GW 572016; GW 572016X; GW572016; Lapatinib (INN); Tykerb (TN); Lapatinib, Tykerb, GW572016; N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine; N-{3-CHLORO-4-[(3-FLUOROBENZYL)OXY]PHENYL}-6-[5-({[2-(METHYLSULFONYL)ETHYL]AMINO}METHYL)-2-FURYL]-4-QUINAZOLINAMINE; N-(3-Chloro-4-((3-fluorophenyl)methoxy)phenyl)-6-(5-((2-methylsulfonylethylamino)methyl)-2-furyl)quinazolin-4-amine; N-(3-Chloro-4-{[(3-fluorophenyl)methyl]oxy}phenyl)-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furanyl]-4-quinazolinamine; 4-[[3-Chloro-4-(3-fluorobenzyloxy)phenyl]amino]-6-[5-[[(2-methanesulfonylethyl)amino]methyl]furan-2-yl]quinazoline; Lapatinib (ERBB2 inhibitor)
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Molecular Type
Small molecule
Disease Breast cancer [ICD-11: 2C60] Approved [1]
Structure
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2D MOL

3D MOL

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Formula
C29H26ClFN4O4S
PubChem CID
208908
Canonical SMILES
CS(=O)(=O)CCNCC1=CC=C(O1)C2=CC3=C(C=C2)N=CN=C3NC4=CC(=C(C=C4)OCC5=CC(=CC=C5)F)Cl
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)
InChIKey
BCFGMOOMADDAQU-UHFFFAOYSA-N
CAS Number
CAS 231277-92-2
GDSC
Lapatinib
TTD Drug ID
D08CDI
DrugBank ID
DB01259
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Celastrol      Celastrus strigillosus     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression c-RAF  Molecule Info 
Pathway MAP
Down-regulation Expression HER2  Molecule Info 
Pathway MAP
Down-regulation Expression HSPA4  Molecule Info 
Pathway MAP
                    In-vitro Model SK-BR-3 CVCL_0033 Breast adenocarcinoma Homo sapiens
BT-474 CVCL_0179 Invasive breast carcinoma Homo sapiens
MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
BT-20 CVCL_0178 Invasive breast carcinoma Homo sapiens
MCF-10A CVCL_0598 Healthy Homo sapiens
                    In-vivo Model Four to six week old female NOD-SCID mice received sub-cutaneous 17Beta-estradiol pellet (0.72 mg/day), 2 weeks prior to injection of 5 * 106 BT-474 cells resuspended in 4% Matrigel.
                    Experimental
                    Result(s)		 Celastrol strongly synergized with ErbB2-targeted therapeutics Lapatinib, producing higher cytotoxicity with substantially lower doses of Celastrol.
          Luteolin      Abrus precatorius     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BCL2L11  Molecule Info 
Pathway MAP
Up-regulation Expression CDKN1A  Molecule Info 
Pathway MAP
Up-regulation Expression FOXO3  Molecule Info 
Pathway MAP
Up-regulation Expression GADD45A  Molecule Info 
Pathway MAP
Up-regulation Expression NQO1  Molecule Info 
Pathway MAP
                    In-vitro Model SK-BR-3 CVCL_0033 Breast adenocarcinoma Homo sapiens
ZR-75-1 CVCL_0588 Invasive breast carcinoma Homo sapiens
BT-474 CVCL_0179 Invasive breast carcinoma Homo sapiens
                    In-vivo Model Xenograft nude mice were inoculated subcutaneously with 0.1 mL of cell suspension (ZR-75-1 and BT-474 cells).
                    Experimental
                    Result(s)		 Combination of lapatinib and luteolin enhances the therapeutic efficacy of lapatinib on human breast cancer through the FOXO3a/NQO1 pathway.
Target and Pathway
Target(s) Elongation factor 2 kinase (eEF-2K)  Molecule Info  [4]
Epidermal growth factor receptor (EGFR)  Molecule Info  [5]
Tyrosine kinase receptor Erbb2 (HER2)  Molecule Info  [5]
KEGG Pathway ErbB signaling pathway Click to Show/Hide
2 Calcium signaling pathway
3 HIF-1 signaling pathway
4 Focal adhesion
5 Adherens junction
6 Pathways in cancer
7 Proteoglycans in cancer
8 MicroRNAs in cancer
9 Pancreatic cancer
10 Endometrial cancer
11 Prostate cancer
12 Bladder cancer
13 Non-small cell lung cancer
14 Central carbon metabolism in cancer
15 MAPK signaling pathway
16 Ras signaling pathway
17 Rap1 signaling pathway
18 Cytokine-cytokine receptor interaction
19 FoxO signaling pathway
20 Endocytosis
21 PI3K-Akt signaling pathway
22 Dorso-ventral axis formation
23 Gap junction
24 Regulation of actin cytoskeleton
25 GnRH signaling pathway
26 Estrogen signaling pathway
27 Oxytocin signaling pathway
28 Epithelial cell signaling in Helicobacter pylori infection
29 Hepatitis C
30 Glioma
31 Melanoma
32 Choline metabolism in cancer
33 AMPK signaling pathway
NetPath Pathway TCR Signaling Pathway Click to Show/Hide
2 IL4 Signaling Pathway
3 EGFR1 Signaling Pathway
Panther Pathway Cadherin signaling pathway Click to Show/Hide
2 EGF receptor signaling pathway
Pathwhiz Pathway Phosphatidylinositol Phosphate Metabolism Click to Show/Hide
Pathway Interaction Database ErbB4 signaling events Click to Show/Hide
2 ErbB2/ErbB3 signaling events
3 ErbB receptor signaling network
4 a6b1 and a6b4 Integrin signaling
5 Validated targets of C-MYC transcriptional repression
6 LPA receptor mediated events
7 Signaling events mediated by PTP1B
8 Arf6 signaling events
9 Signaling events mediated by TCPTP
10 Thromboxane A2 receptor signaling
11 SHP2 signaling
12 Regulation of Telomerase
13 EGF receptor (ErbB1) signaling pathway
14 EGFR-dependent Endothelin signaling events
15 Posttranslational regulation of adherens junction stability and dissassembly
16 Direct p53 effectors
17 ErbB1 downstream signaling
18 Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling
19 E-cadherin signaling in keratinocytes
20 Internalization of ErbB1
21 Stabilization and expansion of the E-cadherin adherens junction
22 Syndecan-3-mediated signaling events
Reactome SHC1 events in ERBB2 signaling Click to Show/Hide
2 PLCG1 events in ERBB2 signaling
3 PIP3 activates AKT signaling
4 GRB2 events in ERBB2 signaling
5 PI3K events in ERBB2 signaling
6 Constitutive Signaling by Aberrant PI3K in Cancer
7 Sema4D induced cell migration and growth-cone collapse
8 RAF/MAP kinase cascade
9 Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants
10 GRB2 events in EGFR signaling
11 GAB1 signalosome
12 SHC1 events in EGFR signaling
13 EGFR downregulation
14 EGFR Transactivation by Gastrin
15 Constitutive Signaling by EGFRvIII
WikiPathways DNA Damage Response (only ATM dependent) Click to Show/Hide
2 ErbB Signaling Pathway
3 EGF/EGFR Signaling Pathway
4 Focal Adhesion
5 Extracellular vesicle-mediated signaling in recipient cells
6 Bladder Cancer
7 Signaling by ERBB2
8 Integrated Pancreatic Cancer Pathway
9 Signaling Pathways in Glioblastoma
10 Leptin signaling pathway
11 miR-targeted genes in muscle cell - TarBase
12 Semaphorin interactions
13 Regulation of Actin Cytoskeleton
14 MAPK Signaling Pathway
15 Aryl Hydrocarbon Receptor Pathway
16 TCA Cycle Nutrient Utilization and Invasiveness of Ovarian Cancer
17 Hair Follicle Development: Cytodifferentiation (Part 3 of 3)
18 Hair Follicle Development: Induction (Part 1 of 3)
19 Signaling by ERBB4
20 Gastrin-CREB signalling pathway via PKC and MAPK
21 PIP3 activates AKT signaling
22 Nanoparticle-mediated activation of receptor signaling
23 Aryl Hydrocarbon Receptor
24 Spinal Cord Injury
25 Gastric cancer network 2
26 AGE/RAGE pathway
27 Arylhydrocarbon receptor (AhR) signaling pathway
28 miR-targeted genes in lymphocytes - TarBase
29 miR-targeted genes in epithelium - TarBase
30 Integrated Breast Cancer Pathway
31 Signaling by EGFR
32 L1CAM interactions
References
Reference 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5692).
Reference 2 Anticancer activity of Celastrol in combination with ErbB2-targeted therapeutics for treatment of ErbB2-overexpressing breast cancers. Cancer Biol Ther. 2011 Jan 15;11(2):263-76.
Reference 3 Combination of lapatinib and luteolin enhances the therapeutic efficacy of lapatinib on human breast cancer through the FOXO3a/NQO1 pathway. Biochem Biophys Res Commun. 2020 Oct 20;531(3):364-371.
Reference 4 Inhibition of eEF-2 kinase sensitizes human nasopharyngeal carcinoma cells to lapatinib-induced apoptosis through the Src and Erk pathways.BMC Cancer. 2016 Oct 19;16(1):813.
Reference 5 Triple negative breast cancer--current status and prospective targeted treatment based on HER1 (EGFR), TOP2A and C-MYC gene assessment. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2009 Mar;153(1):13-7.
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