Foretinib (GSK1363089) is an ATP-competitive inhibitor of HGFR and VEGFR, mostly for Met and KDR with IC50 of 0.4 nM and 0.9 nM in cell-free assays. Less potent against Ron, Flt-1/3/4, Kit, PDGFRα/β and Tie-2, and little activity to FGFR1 and EGFR. Phase 2.
Foretinib is a multikinase inhibitor that targets MET and VEGFR2 and also exhibits an inhibitory effect against KIT, Flt-3, PDGFRb, and Tie-2.
XL880 (GSK1363089, EXEL-2880) is an ATP-competitive inhibitor of MET and KDR with IC50 of 0.4 nM and 0.9 nM, respectively.
Foretinib (GSK1363089) is an ATP-competitive inhibitor of hepatocyte growth factor (HGF) and Vascular endothelial growth factor (VEGF) Receptor Tyrosine Kinases.
ChEBI: N1'-[3-fluoro-4-[[6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-quinolinyl]oxy]phenyl]-N1-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide is an aromatic ether.
Foretinib has also shown to be effective against ROS1 mutations especially when acquired with crizotinib resistance. A clinical trial investigating the dosing and safety profile of combining foretinib and erlotinib was designed for advanced pretreated NSCLC patients.
In vitro, foretinib blocks activation of MET and VEGFR2-induced signaling pathways. In vivo experiments show a dose-dependent decrease in tumor burden in a lung metastasis experimental model.
[1] qian f1, engst s, yamaguchi k, yu p, won ka, mock l, lou t, tan j, li c, tam d, lougheed j, yakes fm, bentzien f, xu w, zaks t, wooster r,greshock j, joly ah. inhibition of tumor cell growth, invasion, and metastasis by exel-2880 (xl880, gsk1363089), a novel inhibitor of hgf and vegf receptor tyrosine kinases. cancer res. 2009 oct 15;69(20):8009-16. doi: 10.1158/0008-5472.can-08-4889.
