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 Cc1ccc(F)c(NC(=O)Nc2ccc(-c3cccc4[nH]nc(N)c34)cc2)c1;
	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]

The substance has been used as part of a chemical cocktail to turn old and senescent human cells back into young ones (as measured by transcriptomic age), without turning them all the way back into undifferentiated stem cells.^[3]

References

^ 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.
^ 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): 1007–1013. doi:10.1158/1535-7163.MCT-05-0359. PMID 16648572.
^ Yang JH, Petty CA, Dixon-McDougall T, Lopez MV, Tyshkovskiy A, Maybury-Lewis S, et al. (July 2023). "Chemically induced reprogramming to reverse cellular aging". Aging. 15 (13): 5966–5989. doi:10.18632/aging.204896. PMC 10373966. PMID 37437248.

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[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): 1007–1013. doi:10.1158/1535-7163.MCT-05-0359. PMID 16648572.

[3] Yang JH, Petty CA, Dixon-McDougall T, Lopez MV, Tyshkovskiy A, Maybury-Lewis S, et al. (July 2023). "Chemically induced reprogramming to reverse cellular aging". Aging. 15 (13): 5966–5989. doi:10.18632/aging.204896. PMC 10373966. PMID 37437248.

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