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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-? 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.

SUBMITTER: Paunescu E

PROVIDER: S-EPMC4360145 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Improved angiostatic activity of dasatinib by modulation with hydrophobic chains.

Păunescu Emilia E Clavel Catherine M CM Nowak-Sliwinska Patrycja P Griffioen Arjan W AW Dyson Paul J PJ

ACS medicinal chemistry letters 20150130 3

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 perfluorina ...[more]

PMID: 25815152

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