ABT-869 (Linifanib) is an aminobenzopyrazole-based, orally available, ATP-competitive receptor tyrosine kinase inhibitor with IC50 potency against KDR, FLT1, CSF-1R, FLT3, and PDGFRb of 4 nM, 3 nM, 3 nM, 4 nM, and 66 nM, respectively. It is highly selective (> 1uM) against unrelated tyrosine kinases and serine/threonine kinases. [1] In cellular assays, ABT-689 exhibited potency against ligand-induced PDGFRbeat, KIT, and CSF-1R phosphorylation, with IC50s of 2, 31, and 10 nM, respectively.

In vivo, ABT-869 is orally effective in a wide range of human xenograft models, including MV4-11, HT1080, H526, DLD-1, A431, MX-1, MDA-231, MDA-435LM, and glioma 9L. [2] ABT-869 displays antiproliferative and apoptotic effects on cancer cells dependent on mutant kinases, such as FLT3. Consequently, ABT-869 is in clinical studies for the treatment of acute myeloid leukemia (AML). [3, 4] ABT-689 has been shown to induce apoptosis through an AKT and GSK-3beta-dependent pathway, thus suggesting that combination therapies with GSK-3beta inhibitors may be a promising approach to AML treatment. [3]