title: Improved angiostatic activity of dasatinib by modulation with hydrophobic chains.
abstract: Dasatinib is an orally active nonselective tyrosine kinase inhibitor used to treat certain types of adult leukemia. By inhibiting PDGFR-β and SFKs in both tumor cells and tumor-associated endothelial cells, dasatinib inhibits tumor growth and angiogenesis. Herein, dasatinib derivatives modified with hydrophobic chains were prepared and evaluated for their in vitro antiproliferative selectivity and their in vivo antiangiogenic activity. For one of the derivatives, modified with a long perfluorinated chain, a significant enhancement in antiangiogenic activity was observed. Combined, these results suggest a possible generic route to modulate the angiostatic activity of drugs.
authors: Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL) , CH-1015 Lausanne, Switzerland.
authors: Emilia
authors: E
authors: Păunescu
authors: Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL) , CH-1015 Lausanne, Switzerland.
authors: Catherine M
authors: CM
authors: Clavel
authors: Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL) , CH-1015 Lausanne, Switzerland.
authors: Patrycja
authors: P
authors: Nowak-Sliwinska
authors: Angiogenesis Laboratory, Department of Medical Oncology, VUMC Cancer Center Amsterdam , 1081 HV Amsterdam, The Netherlands.
authors: Arjan W
authors: AW
authors: Griffioen
authors: Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL) , CH-1015 Lausanne, Switzerland.
authors: Paul J
authors: PJ
authors: Dyson
keywords: Dasatinib; angiogenesis; antiangiogenic drugs; kinase inhibitors; medicinal chemistry