PCI-29732 is a multi-kinase inhibitor.1 It inhibits the Tec family kinase BTK and the Src family kinases LCK and LYN (Kis = 8.2, 4.6, and 2.5 nM, respectively), as well as the activity of three receptor tyrosine kinases and seven non-receptor tyrosine kinases by greater than 90% in a panel of over 100 kinases at 10 ?M. PCI-29732 inhibits calcium flux in Ramos B cells and phosphorylation of phospholipase C?1 (PLC?1) with IC50 values of 0.53 and 0.33 ?M, respectively. It is cytotoxic to S1-MI-80, H460/MX20, and KBv200 cancer cells overexpressing the ATP-binding cassette transporter (IC50s = 7.8, 6.3, and 6.02 ?M, respectively).2 PCI-29732 (20 mg/kg), in combination with the DNA topoisomerase I inhibitor topotecan , reduces tumor growth in an H460/MX20 mouse xenograft model.
1.Pan, Z., Scheerens, H., Li, S.J., et al.Discovery of selective irreversible inhibitors for Bruton's tyrosine kinaseChemMedChem2(1)58-61(2007) 2.Ge, C., Wang, F., Ciu, C., et al.PCI29732, a Bruton's tyrosine kinase inhibitor, enhanced the efficacy of conventional chemotherapeutic agents in ABCG2-overexpressing cancer cellsCell. Physiol. Biochem.48(6)2302-2317(2018)