Cat. No. Name Size Price Add Cart
KI0047Linifanib5 mg$192
Linifanib10 mg$336
Linifanib50 mg$912
Linifanib200 mg$2672

Chemical Characteristic

Product NameLinifanib
SynonymsABT-869
CAS No.796967-16-3
Molecular Weight 375.41
FormulaC21H18FN5O
Chemical Name1-(4-(3-amino-1H-indazol-4-yl)phenyl)-3-(2-fluoro-5-methylphenyl)urea
SmilesN(C(=O)Nc1c(ccc(c1)C)F)c1ccc(cc1)c1c2c(n[nH]c2ccc1)N
Chemical Structure

Biological activities

Linifanib is a receptor tyrosine kinase (RTK) inhibitor. Linifanib inhibits KDR, FLT1, PDGFR-b, CSF-1R, KIT and FLT3 with IC50 of 4, 3, 66, 3, 14 and 4 nM, respectively. Linifanib also is a potent inhibitor of members of the vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptor families. Phosphorylation of KDR induced by VEGF is inhibited by linifanib with an IC50 of 4 nM in 3T3 murine fibroblasts engineered to express human KDR. [1] Linifanib suppresses FMS-like receptor tyrosine kinase 3 (FLT3) signaling. Linifanib has antiproliferative and apoptotic effects in vitro on internal tandem duplication (ITD) mutant cell lines. The IC50 of linifanib on ITD cells is 0.55 nM, whereas the IC50 for wild type (WT) cells is 6 µM. Linifanib inhibits phosphorylation of Akt and GSK3b in Ba/F3 FLT3 ITD mutant cells. Linifanib inhibits proliferation in FLT3 ITD-positive human leukemia cell lines MV-411 and Molm-14 at an IC50 less than of 10 nM. Furthermore, linifanib causes cell-cycle arrest and apoptosis through decreased expression of cyclins D and E and increased expression of cyclindependent inhibitors p21waf1/cip and p27kip1. [2] Linifanib inhibits the phosphorylation of FLT3, STAT5, and ERK, as well as Pim-1 expression in MV-4-11 and MOLM-13 cells with IC50 range from 1 to 10 nM. Linifanib inhibits the proliferation of MV-4-11 and MOLM-13 cells with IC50 of 4 and 6 nM, respectively. In normal human blood spiked with acute myeloid leukemia (AML) cells, linifanib inhibits phosphorylation of FLT3, STAT5, and ERK, and decreases Pim-1 expression. [3] In vivo, xenograft experiments with NOD/SCID mice injected with ITD mutant cells and treated daily orally by gavage with linifanib have a decreased rate of leukemia progression compared with untreated mice. [2] Linifanib dose-dependently inhibits MV-4-11 and MOLM-13 ?ank tumor growth, prevents tumor formation, regresses established MV-4-11 xenografts, and increases survival by 20 weeks in an MV-4-11 engraftment model. In tumors, linifanib inhibits FLT3 phosphorylation, induces apoptosis and decreases proliferation (Ki67). [3]

Protocols

Linifanib is dissolved in DMSO to a concentration of 10 mM and stored in aliquots at -80°C for use in vitro experiments.[2]

References

[1] Albert DH, et al. Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor. Mol Cancer Ther. 2006, 5(4): 995-1006.
[2] Hernandez-Davies JE, et al. The multitargeted receptor tyrosine kinase inhibitor linifanib (ABT-869) induces apoptosis through an Akt and glycogen synthase kinase 3β-dependent pathway. Mol Cancer Ther. 2011, 10(6): 949-959.
[3] Shankar DB, et al. ABT-869, a multitargeted receptor tyrosine kinase inhibitor: inhibition of FLT3 phosphorylation and signaling in acute myeloid leukemia. Blood. 2007, 109(8): 3400-3408.

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