Synthesis and biological evaluation of a fluorine-18 derivative of dasatinib.

Abstract

Tyrosine kinases often play pivotal roles in the pathogenesis of cancer and are good candidates for therapeutic intervention and targeted molecular imaging. The precursor synthesis, radiosynthesis, and biological characterization of a fluorine-18 analog of dasatinib, a multitargeted kinase inhibitor, are reported. Compound 5 potently inhibits Abl, Src, and Kit kinases and inhibits K562 and M07e/p210bcr-abl human leukemic cell growth. Using positron emission tomography, we visualized K562 tumor xenografts in mice with [18F]-5.

• Authors: Darren R Veach, Mohammad Namavari, Nagavarakishore Pillarsetty, Elmer B Santos, Tatiana Beresten-Kochetkov, Caryl Lambek, Blesida J Punzalan, Christophe Antczak, Peter M Smith-Jones, Hakim Djaballah, Bayard Clarkson, Steven M Larson
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 50 Issue 23 Pg. 5853-7 (Nov 15 2007) ISSN: 0022-2623 [Print] United States
• PMID: 17956080 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Fluorine Radioisotopes
• Pyrimidines
• Radiopharmaceuticals
• Thiazoles
• Protein-Tyrosine Kinases
• Proto-Oncogene Proteins c-kit
• Fusion Proteins, bcr-abl
• src-Family Kinases
• Dasatinib

Topics

• Animals
• Catalytic Domain
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dasatinib
• Fluorine Radioisotopes
• Fusion Proteins, bcr-abl
• Humans
• Mice
• Mice, Nude
• Positron-Emission Tomography
• Protein-Tyrosine Kinases (antagonists & inhibitors)
• Proto-Oncogene Proteins c-kit (metabolism)
• Pyrimidines (chemical synthesis, pharmacokinetics, pharmacology)
• Radiopharmaceuticals (chemical synthesis, pharmacokinetics, pharmacology)
• Thiazoles (chemical synthesis, pharmacokinetics, pharmacology)
• Transplantation, Heterologous
• src-Family Kinases (antagonists & inhibitors)