Drug Information

Drug (ID: DG00115) and It's Reported Resistant Information
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)
    Click to Show/Hide
Indication
In total 1 Indication(s)
Breast cancer [ICD-11: 2C60]
Approved
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
Breast cancer [ICD-11: 2C60]
[2]
Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
Breast cancer [ICD-11: 2C60]
[3]
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases)
Breast cancer [ICD-11: 2C60]
[4]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
[5]
Target Epidermal growth factor receptor (EGFR) EGFR_HUMAN [1]
Erbb2 tyrosine kinase receptor (HER2) ERBB2_HUMAN [1]
Eukaryotic elongation factor 2 kinase (eEF-2K) EF2K_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C29H26ClFN4O4S
IsoSMILES
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
PubChem CID
208908
ChEBI ID
CHEBI:49603
TTD Drug ID
D08CDI
VARIDT ID
DR00120
DrugBank ID
DB01259
Type(s) of Resistant Mechanism of This Drug due to Structure Alteration
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
Click to Show/Hide the Resistance Disease of This Class
Breast cancer [ICD-11: 2C60]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: GTPase Hras (HRAS) [6]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Molecule Alteration Missense mutation
p.G12S
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.24  Å
PDB: 4OBE
Mutant Type Structure Method: X-ray diffraction Resolution: 1.71  Å
PDB: 7TLK
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.85
TM score: 0.93473
Amino acid change:
G12S
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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M
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20
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30
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40
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50
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C
C
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D
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A
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60
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70
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80
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C
C
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90
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F
F
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110
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G
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120
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130
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140
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F
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A
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150
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G
G
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160
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V
V
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H
H
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E
E
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K
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Circulating-free DNA assay
Experiment for
Drug Resistance		 Positron emission tomography/Computed tomography assay
Mechanism Description Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
References
Ref 1 miR 494 inhibits cancer initiating cell phenotypes and reverses resistance to lapatinib by downregulating FGFR2 in HER2 positive gastric cancer. Int J Mol Med. 2018 Aug;42(2):998-1007. doi: 10.3892/ijmm.2018.3680. Epub 2018 May 16.
Ref 2 Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature. 2013 May 2;497(7447):108-12. doi: 10.1038/nature12065. Epub 2013 Apr 7.
Ref 3 Combination therapy of Lapatinib/Letrozole-based protein-vitamin nanoparticles to enhance the therapeutic effectiveness in drug-resistant breast cancer. Colloids Surf B Biointerfaces. 2025 Mar;247:114399.
Ref 4 Breast Cancer Anti-Estrogen Resistance 4 (BCAR4) Drives Proliferation of IPH-926 lobular Carcinoma Cells. PLoS One. 2015 Aug 28;10(8):e0136845. doi: 10.1371/journal.pone.0136845. eCollection 2015.
Ref 5 Activity of a novel HER2 inhibitor, poziotinib, for HER2 exon 20 mutations in lung cancer and mechanism of acquired resistance: An in vitro studyLung Cancer. 2018 Dec;126:72-79. doi: 10.1016/j.lungcan.2018.10.019. Epub 2018 Oct 17.
Ref 6 Circulating-free DNA Mutation Associated with Response of Targeted Therapy in Human Epidermal Growth Factor Receptor 2-positive Metastatic Breast Cancer. Chin Med J (Engl). 2017 Mar 5;130(5):522-529. doi: 10.4103/0366-6999.200542.

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