BIBF 1120 is an indolinone derivative potently blocking VEGF receptor (VEGFR), PDGFR and FGFR kinase activity in enzymatic assays (IC50, 20-100 nmol/L). BIBF 1120 inhibits mitogen-activated protein kinase and Akt signaling pathways in three cell types contributing to angiogenesis, endothelial cells, pericytes, and smooth muscle cells, resulting in inhibition of cell proliferation (EC50, 10-80 nmol/L) and apoptosis. In all tumor models tested thus far, including human tumor xenografts growing in nude mice and a syngeneic rat tumor model, BIBF 1120 is highly active at well-tolerated doses (25-100 mg/kg daily p.o.), as measured by magnetic resonance imaging of tumor perfusion after 3 days, reducing vessel density and vessel integrity after 5 days, and inducing profound growth inhibition.

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3. A clinical phase I, pharmacokinetik (PK), and pharmacodynamic (PD) study of BIBF1120 in advanced cancer patients. Mross K, Baas F, Medinger M, et al. Molecular Targets and Cancer Therapeutics, 16th EORTC-NCI-AACR Symposium, September 28 to October 1, 2004, Geneva, Switzerland.

4. BIBF 1120 - a novel, small molecule triple angiokinase inhibitor: profiling as a clinical candidate for cancer therapy. Hilberg F, Tontsch-Grunt U, Colbatzky F, et al. Molecular Targets and Cancer Therapeutics, 16th EORTC-NCI-AACR Symposium, September 28 to October 1, 2004, Geneva, Switzerland.