Nilotinib

Nilotinib
Nilotinib
Systematic (IUPAC) name
4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)- 5-(trifluoromethyl)phenyl]-3- [(4-pyridin-3-ylpyrimidin-2-yl) amino]benzamide
Clinical data
AHFS/Drugs.com monograph
MedlinePlus a608002
Licence data EMA:Link, US FDA:link
Pregnancy cat. D(US)
Legal status POM (UK) ℞-only (US)
Routes Oral
Pharmacokinetic data
Bioavailability 30%
Protein binding 98%
Metabolism hepatic
Half-life 17 h
Excretion biliary
Identifiers
CAS number 641571-10-0(base) N
ATC code L01XE08
PubChem CID 644241
DrugBank DB04868
ChemSpider 559260 YesY
UNII F41401512X YesY
KEGG D08953 YesY
ChEBI CHEBI:52172 YesY
ChEMBL CHEMBL255863 YesY
Chemical data
Formula C28H22F3N7O 
Mol. mass 529.5245 g/mol
SMILES eMolecules & PubChem
 N(what is this?)  (verify)

Nilotinib (AMN107, trade name Tasigna), in the form of the hydrochloride monohydrate salt, is a tyrosine kinase inhibitor approved for the treatment of chronic myelogenous leukemia[1].

Contents

Uses

Crystal structure of Abl kinase domain (blue) in complex with nilotinib (red)

It was approved as Tasigna in the USA and the EU for drug-resistant chronic myelogenous leukemia (CML).[2] In June 2006, a Phase I clinical trial found nilotinib has a relatively favorable safety profile and shows activity in cases of CML resistant to treatment with imatinib (Gleevec), another tyrosine kinase inhibitor currently used as a first-line treatment.[3] In that study 92% of patients (already resistant or unresponsive to imatinib) achieved a normal white blood cell counts after five months of treatment.[4] The drug carries a black box warning for possible heart complications.[5][6]

Pharmacology

Nilotinib inhibits the kinases BCR-ABL,[7] KIT, LCK, EPHA3, EPHA8, DDR1, DDR2, PDGFRB, MAPK11 and ZAK.[8]

See also

  • Discovery and development of Bcr-Abl tyrosine kinase inhibitors

References

  1. ^ ""Cancer Drug Information: Nilotinib". http://www.cancer.gov/cancertopics/druginfo/nilotinib. 
  2. ^ Novartis 29/10/2007 Press Release.
  3. ^ Kantarjian H et al. (2006). "Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL". N Engl J Med 354 (24): 2542–51. doi:10.1056/NEJMoa055104. PMID 16775235. 
  4. ^ "Patients with treatment-resistant leukemia achieve high responses to Tasigna (nilotinib) in first published clinical trial results". MediaReleases (Novartis). 2006-06-14. http://cws.huginonline.com/N/134323/PR/200606/1056533_5.html. Retrieved 2009-08-04. 
  5. ^ "FDA Approves Tasigna for Treatment of Philadelphia Chromosome Positive Chronic Myeloid Leukemia". U.S. Food and Drug Administration. 2007-10-30. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm109017.htm. Retrieved 2009-08-04. 
  6. ^ "Prescribing information for Tasigna (nilotinib) Capsules" (PDF). NDA 022068. U.S. FDA. 2007-10-29. http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022068lbl.pdf. Retrieved 2009-08-04. 
  7. ^ Weisberg E, Manley P, Mestan J, Cowan-Jacob S, Ray A, Griffin JD (June 2006). "AMN107 (nilotinib): a novel and selective inhibitor of BCR-ABL". Br. J. Cancer 94 (12): 1765–9. doi:10.1038/sj.bjc.6603170. PMC 2361347. PMID 16721371. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2361347. 
  8. ^ Manley, PW; Drueckes, P; Fendrich, G; Furet, P; Liebetanz, J; Martiny-Baron, G; Mestan, J; Trappe, J et al. (2010). "Extended kinase profile and properties of the protein kinase inhibitor nilotinib". Biochimica et biophysica acta 1804 (3): 445–53. doi:10.1016/j.bbapap.2009.11.008. PMID 19922818. 
v · d · eTargeted therapy / extracellular chemotherapeutic agents/antineoplastic agents (L01)
CI monoclonal antibodies ("-mab")
Others for solid tumors
Tyrosine-kinase inhibitors ("-nib")

ErbB: HER1/EGFR (Erlotinib, Gefitinib, Vandetanib) • HER1/EGFR and HER2/neu (Afatinib, Lapatinib, Neratinib)

RTK class III: C-kit and PDGFR (Axitinib, Pazopanib, Sunitinib, Sorafenib, Toceranib) • FLT3 (Lestaurtinib)

VEGFR (Axitinib, Cediranib, Pazopanib, Regorafenib, Semaxanib, Sorafenib, Sunitinib, Toceranib, Vandetanib)
Other
fusion protein against VEGF (Aflibercept) • proapoptotic peptide against ANXA2 and prohibitin (Adipotide) • exotoxin against IL-2 (Denileukin diftitox)

M: NEO

tsoc, mrkr

tumr, epon, para

drug (L1i/1e/V03)


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