Linifanib

Linifanib
Clinical data
ATC code	None;
Legal status
Legal status	Investigational;
Identifiers
	IUPAC name 1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methylphenyl)urea;
CAS Number	796967-16-3;
PubChem CID	11485656;
IUPHAR/BPS	5657;
ChemSpider	9660475 ;
UNII	CO93X137CW;
KEGG	D09635 ;
ChEBI	CHEBI:91435;
ChEMBL	ChEMBL223360 ;
CompTox Dashboard (EPA)	DTXSID40229834 ;
ECHA InfoCard	100.206.772
Chemical and physical data
Formula	C17H15FN5O
Molar mass	324.339 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=CC(=C(C=C1)F)NC(=O)NC2=CC=C(C=C2)C3=C4C(=CC=C3)NN=C4N;
	InChI 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

Albert, D. H.; Tapang, P.; Magoc, T. J.; Pease, L. J.; Reuter, D. R.; Wei, R. Q.; Li, J.; Guo, J.; Bousquet, P. F.; Ghoreishi-Haack, N. S.; Wang, B.; Bukofzer, G. T.; Wang, Y. C.; Stavropoulos, J. A.; Hartandi, K.; Niquette, A. L.; Soni, N.; Johnson, E. F.; McCall, J. O.; Bouska, J. J.; Luo, Y.; Donawho, C. K.; Dai, Y.; Marcotte, P. A.; Glaser, K. B.; Michaelides, M. R.; Davidsen, S. K. (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.
Guo, J.; Marcotte, P. A.; McCall, J. O.; Dai, Y.; Pease, L. J.; Michaelides, M. R.; Davidsen, S. K.; Glaser, K. B. (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): 1007–1013. doi:10.1158/1535-7163.MCT-05-0359. PMID 16648572.

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[1] Albert, D. H.; Tapang, P.; Magoc, T. J.; Pease, L. J.; Reuter, D. R.; Wei, R. Q.; Li, J.; Guo, J.; Bousquet, P. F.; Ghoreishi-Haack, N. S.; Wang, B.; Bukofzer, G. T.; Wang, Y. C.; Stavropoulos, J. A.; Hartandi, K.; Niquette, A. L.; Soni, N.; Johnson, E. F.; McCall, J. O.; Bouska, J. J.; Luo, Y.; Donawho, C. K.; Dai, Y.; Marcotte, P. A.; Glaser, K. B.; Michaelides, M. R.; Davidsen, S. K. (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, P. A.; McCall, J. O.; Dai, Y.; Pease, L. J.; Michaelides, M. R.; Davidsen, S. K.; Glaser, K. B. (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): 1007–1013. doi:10.1158/1535-7163.MCT-05-0359. PMID 16648572.