Linifanib

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Linifanib
Linifanib skeletal.svg
Clinical data
ATC code
  • None
Legal status
Legal status
  • Investigational
Identifiers
  • 1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methylphenyl)urea
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.206.772 Edit this at Wikidata
Chemical and physical data
FormulaC17H15FN5O
Molar mass324.339 g·mol−1
3D model (JSmol)
  • CC1=CC(=C(C=C1)F)NC(=O)NC2=CC=C(C=C2)C3=C4C(=CC=C3)NN=C4N
  • InChI=1S/C21H18FN5O/c1-12-5-10-16(22)18(11-12)25-21(28)24-14-8-6-13(7-9-14)15-3-2-4-17-19(15)20(23)27-26-17/h2-11H,1H3,(H3,23,26,27)(H2,24,25,28)
  • Key:MPVGZUGXCQEXTM-UHFFFAOYSA-N
  (verify)

Linifanib (ABT-869) is a structurally novel, potent inhibitor of receptor tyrosine kinases (RTK), vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) with IC50 of 0.2, 2, 4, and 7 nM for human endothelial cells, PDGF receptor beta (PDGFR-β), KDR, and colony stimulating factor 1 receptor (CSF-1R), respectively. It has much less activity (IC50s > 1 μM) against unrelated RTKs, soluble tyrosine kinases, or serine/threonine kinases. In vivo linifanib is effective orally in mechanism-based murine models of VEGF-induced uterine edema (ED50 = 0.5 mg/kg) and corneal angiogenesis (>50%inhibition, 15 mg/kg).[1][2]

References[edit]

  1. ^ Albert DH, Tapang P, Magoc TJ, Pease LJ, Reuter DR, Wei RQ, et al. (April 2006). "Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor". Molecular Cancer Therapeutics. 5 (4): 995–1006. doi:10.1158/1535-7163.MCT-05-0410. PMID 16648571.
  2. ^ Guo J, Marcotte PA, McCall JO, Dai Y, Pease LJ, Michaelides MR, et al. (April 2006). "Inhibition of phosphorylation of the colony-stimulating factor-1 receptor (c-Fms) tyrosine kinase in transfected cells by ABT-869 and other tyrosine kinase inhibitors". Molecular Cancer Therapeutics. 5 (4): 1007–13. doi:10.1158/1535-7163.MCT-05-0359. PMID 16648572.