Drug Information

Drug (ID: DG00056) and It's Reported Resistant Information
Name
Ceritinib
Synonyms
Ceritinib; LDK378; 1032900-25-6; ZYKADIA; NVP-LDK378-NX; LDK-378; UNII-K418KG2GET; LDK378(Ceritinib); LDK 378; Eritinib (LDK378); 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine; K418KG2GET; CHEMBL2403108; CHEBI:78432; AK174337; ceritinib; C28H36ClN5O3S; 5-Chloro-N2-[2-isopropoxy-5-Methyl-4-(4-piperidyl)phenyl]-N4-(2-isopropylsulfonylphenyl)pyriMidine-2,4-diaMine; 5-Chloro-N2-(5-methyl-4-(piperidin-4-yl)-2-(propan-2-yloxy)phenyl)-N4-(2-(propane-2-sulfonyl)phenyl)pyrim
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Indication
In total 1 Indication(s)
Lung cancer [ICD-11: 2C25]
Approved
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
Lung cancer [ICD-11: 2C25]
[1]
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
Diffuse large B-cell lymphoma [ICD-11: 2A81]
[2]
Target ALK tyrosine kinase receptor (ALK) ALK_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C28H36ClN5O3S
IsoSMILES
CC1=CC(=C(C=C1C2CCNCC2)OC(C)C)NC3=NC=C(C(=N3)NC4=CC=CC=C4S(=O)(=O)C(C)C)Cl
InChI
1S/C28H36ClN5O3S/c1-17(2)37-25-15-21(20-10-12-30-13-11-20)19(5)14-24(25)33-28-31-16-22(29)27(34-28)32-23-8-6-7-9-26(23)38(35,36)18(3)4/h6-9,14-18,20,30H,10-13H2,1-5H3,(H2,31,32,33,34)
InChIKey
VERWOWGGCGHDQE-UHFFFAOYSA-N
PubChem CID
57379345
ChEBI ID
CHEBI:78432
TTD Drug ID
D04LVK
VARIDT ID
DR00228
DrugBank ID
DB09063
Type(s) of Resistant Mechanism of This Drug due to Structure Alteration
  ADTT: Aberration of the Drug's Therapeutic Target
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
Lung cancer [ICD-11: 2C25]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: ALK tyrosine kinase receptor (ALK) [1]
Resistant Disease Non-small cell lung cancer [ICD-11: 2C25.Y]
 Disease Info 
Molecule Alteration Missense mutation
p.L1196M
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.75  Å
PDB: 3AOX
Mutant Type Structure Method: X-ray diffraction Resolution: 1.66  Å
PDB: 4CLJ
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.69
TM score: 0.97734
Amino acid change:
L1196M
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Next-generation sequencing assay
Experiment for
Drug Resistance		 Computerized tomography assay
Mechanism Description Non-small cell lung cancers (NSCLC) harboring anaplastic lymphoma kinase (ALk) gene rearrangements invariably develop resistance to the ALk tyrosine kinase inhibitor (TkI) crizotinib. In particular, ceritinib effectively inhibits ALk harboring L1196M, G1269A, I1171T and S1206Y mutations, and a co-crystal of ceritinib bound to ALk provides structural bases for this increased potency.
References
Ref 1 The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer. Cancer Discov. 2014 Jun;4(6):662-673. doi: 10.1158/2159-8290.CD-13-0846. Epub 2014 Mar 27.
Ref 2 Treatment Efficacy and Resistance Mechanisms Using the Second-Generation ALK Inhibitor AP26113 in Human NPM-ALK-Positive Anaplastic Large Cell Lymphoma .Mol Cancer Res. 2015 Apr;13(4):775-83. doi: 10.1158/1541-7786.MCR-14-0157. Epub 2014 Nov 24. 10.1158/1541-7786.MCR-14-0157

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