4MK

5-chloro-N~2~-[5-methyl-4-(piperidin-4-yl)-2-(propan-2-yloxy)phenyl]-N~4~-[2-(propan-2-ylsulfonyl)phenyl]pyrimidine-2,4-diamine

Created:2013-09-16
Last modified:  2020-05-26

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Chemical Details

Formal Charge0
Atom Count74
Chiral Atom Count0
Bond Count77
Aromatic Bond Count18
2D diagram of 4MK

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Chemical Component Summary

Name5-chloro-N~2~-[5-methyl-4-(piperidin-4-yl)-2-(propan-2-yloxy)phenyl]-N~4~-[2-(propan-2-ylsulfonyl)phenyl]pyrimidine-2,4-diamine
SynonymsCeritinib; LDK378
Systematic Name (OpenEye OEToolkits)5-chloranyl-N2-(5-methyl-4-piperidin-4-yl-2-propan-2-yloxy-phenyl)-N4-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine
FormulaC28 H36 Cl N5 O3 S
Molecular Weight558.135
TypeNON-POLYMER

Chemical Descriptors

TypeProgramVersionDescriptor
SMILESACDLabs12.01O=S(=O)(c1ccccc1Nc2nc(ncc2Cl)Nc3cc(c(cc3OC(C)C)C4CCNCC4)C)C(C)C
SMILESCACTVS3.385CC(C)Oc1cc(C2CCNCC2)c(C)cc1Nc3ncc(Cl)c(Nc4ccccc4[S](=O)(=O)C(C)C)n3
SMILESOpenEye OEToolkits1.7.6Cc1cc(c(cc1C2CCNCC2)OC(C)C)Nc3ncc(c(n3)Nc4ccccc4S(=O)(=O)C(C)C)Cl
Canonical SMILESCACTVS3.385 CC(C)Oc1cc(C2CCNCC2)c(C)cc1Nc3ncc(Cl)c(Nc4ccccc4[S](=O)(=O)C(C)C)n3
Canonical SMILESOpenEye OEToolkits1.7.6 Cc1cc(c(cc1C2CCNCC2)OC(C)C)Nc3ncc(c(n3)Nc4ccccc4S(=O)(=O)C(C)C)Cl
InChIInChI1.03 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)
InChIKeyInChI1.03 VERWOWGGCGHDQE-UHFFFAOYSA-N

Drug Info: DrugBank

DrugBank data are sourced from datasets licensed under a Creative Common's Attribution-NonCommercial 4.0 International License
DrugBank IDDB09063 
NameCeritinib
Groups approved
DescriptionCeritinib is used for the treatment of adults with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) following failure (secondary to resistance or intolerance) of prior crizotinib therapy. About 4% of patients with NSCLC have a chromosomal rearrangement that generates a fusion gene between EML4 (echinoderm microtubule-associated protein-like 4) and ALK (anaplastic lymphoma kinase), which results in constitutive kinase activity that contributes to carcinogenesis and seems to drive the malignant phenotype. Ceritinib exerts its therapeutic effect by inhibiting autophosphorylation of ALK, ALK-mediated phosphorylation of the downstream signaling protein STAT3, and proliferation of ALK-dependent cancer cells. Following treatment with crizotinib (a first-generation ALK inhibitor), most tumours develop drug resistance due to mutations in key "gatekeeper" residues of the enzyme. This occurrence led to development of novel second-generation ALK inhibitors such as ceritinib to overcome crizotinib resistance. The FDA approved ceritinib in April 2014 due to a surprisingly high response rate (56%) towards crizotinib-resistant tumours and has designated it with orphan drug status.
Synonyms
  • Ceritinib
  • Céritinib
  • Ceritinibum
  • N-{2-[(5-chloro-2-{[2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl]amino}pyrimidin-4-yl)amino]phenyl}propane-2-sulfonamide
Brand NamesZykadia
IndicationCeritinib is a kinase inhibitor indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. This indication is approved under accelerated approval based on tumor response rate and duration of response. An improvement in survival or disease-related symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Categories
  • Anaplastic lymphoma kinase (ALK) inhibitors
  • Antineoplastic Agents
  • Antineoplastic and Immunomodulating Agents
  • Bradycardia-Causing Agents
  • Cytochrome P-450 CYP2C9 Inhibitors
ATC-CodeL01ED02
CAS number1032900-25-6

Drug Targets

DrugBank data are sourced from datasets licensed under a Creative Common's Attribution-NonCommercial 4.0 International License
NameTarget SequencePharmacological ActionActions
ALK tyrosine kinase receptorMGAIGLLWLLPLLLSTAAVGSGMGTGQRAGSPAAGPPLQPREPLSYSRLQ...unknownantagonist
Cytochrome P450 2C9MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDI...unknowninhibitor
Cytochrome P450 3A4MALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNI...unknownsubstrate,inhibitor
ATP-dependent translocase ABCB1MDLEGDRNGGAKKKNFFKLNNKSEKDKKEKKPTVSVFSMFRYSNWLDKLY...unknownsubstrate
Drug Info/Drug Targets: DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, Pon A, Banco K, Mak C, Neveu V, Djoumbou Y, Eisner R, Guo AC, Wishart DS. Nucleic Acids Res. 2011 Jan; 39 (Database issue):D1035-41. | PMID:21059682

Related Resource References

Resource NameReference
Pharos CHEMBL2403108
PubChem 57379345
ChEMBL CHEMBL2403108
ChEBI CHEBI:78432
CCDC/CSD SEMGUP