Kinase-mediated trapping of bi-functional conjugates of paclitaxel or vinblastine with thymidine in cancer cells

  • Bioorg Med Chem Lett. 2006 Oct 1;16(19):5194-8. doi: 10.1016/j.bmcl.2006.07.003.
Simon E Aspland  1 ,  Carlo Ballatore ,  Rosario Castillo ,  Joel Desharnais ,  Trisha Eustaquio ,  Philip Goelet ,  Zijian Guo ,  Qing Li ,  David Nelson ,  Chengzao Sun ,  Angelo J Castellino ,  Michael J Newman
Affiliations
  • 1. Acidophil LLC, 2330 W. Joppa Road, Suite 330, Lutherville, MD 21093, USA. [email protected]
PMID: 16870428 DOI: 10.1016/j.bmcl.2006.07.003
Abstract

In the present work, we explore the possibility of introducing selectivity to existing chemotherapeutics via the design of non-pro-drug, bi-functional molecules comprising a microtubule-binding agent and a substrate for a disease-associated kinase. The design, synthesis, and in vitro biological evaluation of paclitaxel-thymidine and vinblastine-thymidine bi-functional conjugates are reported here. This work provides the first account of 'kinase-mediated trapping' of Cancer therapeutics.