Dirk B. Mendel

TL;DR: The pharmacokinetic/pharmacodynamic relationship established for SU11248 in these preclinical studies has aided in the design, selection, and evaluation of dosing regimens being tested in human trials.

TL;DR: The feasibility of selectively targeting c-Met with ATP-competitive small-molecules with high selectivity is demonstrated and the therapeutic potential of targetingc-Met in human cancers is suggested.

TL;DR: SU11248 enhances radiation-induced endothelial cytotoxicity, resulting in tumor vascular destruction and tumor control when combined with fractionated radiotherapy in murine tumor models, and inhibition of angiogenesis well beyond radiation therapy may be a promising treatment paradigm for refractory human neoplasms.

TL;DR: This study provides the first evidence that p.o. administered kinase inhibitors can exhibit activity against a variety of spontaneous malignancies in dogs, and it is likely that such agents will demonstrate comparable antineoplastic activity in people.

TL;DR: The durability of the in vitro activity of SU5416 was shown to be attributable to its long-lasting ability to specifically inhibit VEGF-dependent phosphorylation of Flk-1/KDR and subsequent downstream signaling, althoughSU5416 is not an irreversible inhibitor of FlKDR tyrosine kinase activity.