PRODRUG STRATEGIES

Since 2003 the Group of Nucleoside and Analogues develops a new prodrug approach designed to modulate the water solubility, protein binding, blood-brain barrier penetration, oral bioavailability and/or the specific action of a drug against a specific cellular target. This technology has been applied to improve the properties of drugs of different nature, directed against a variety of therapeutic targets. The novelty and applicability of the results has led to a patent, licensed to a European company, which used our technology in the field of novel anti-AIDS drugs.

A new collaboration with the American company Inhibitex (before Fermavir Pharmaceuticals, New York, USA) has been established in order to improve the adverse properties and oral bioavailability of antiviral compounds of the company under clinical development. As a result of this collaboration a second patent has been published.

Relevant publications:

• 2013 - Diez-Torrubia, A.; Cabrera, S.; de Castro, S.; García-Aparicio, C.; Mulder, G.; De Meester, I.; Camarasa, M.J.; Balzarini, J.; Velázquez; S.

  Novel water-soluble prodrugs of acyclovir cleavable by the dipeptidylpeptidase IV (DPP IV/CD26) enzyme. Eur. J. Med. Chem., 2013, 70, 456-468.

• 2012 - Diez-Torrubia, A.; Cabrera, S.; De Meester, I.; Camarasa, M. J.; Balzarini, J.; Velázquez, S.

  Dipeptidyl-peptidase IV-activated prodrugs of anti-Varicella Zoster Virus bicyclic nucleoside analogues containing different self-cleavage spacers systems. ChemMedChem, 2012, 7, 1612-1622.

• 2012 - Diez-Torrubia, A.; Cabrera, S.; Lambeir, A. M.; Balzarini, J.; Camarasa, M. J.; Velázquez, S.

  Dipeptidyl peptidase IV (DPPIV/CD26)-based progrugs of hydroxy-containing drugs. ChemMedChem, 2012, 7, 618-628.

• 2011 - Diez-Torrubia, A.; Balzarini, J.; Andrei, G.; Snoeck, R.; De Meester, I.; Camarasa, M. J.; Velázquez, S.

  Dipeptidyl peptidase IV dependent water-soluble prodrugs of highly liphopilic bicyclic nucleoside analogues J. Med. Chem., 2011, 54, 1927-1942.

• 2010 - Diez-Torrubia, A.; García-Aparicio, C.; Cabrera, S.; De Meester, I.; Balzarini, J.; Camarasa, M. J.; Velázquez, S.

  Application of the dipeptidyl-peptidase IV (DPPIV/CD26) based prodrug approach to different amine-containing drugs. J. Med. Chem. 2010, 53, 559-572.

• 2006 - García Aparicio, C; Bonache, M. C; De Meester, I; San-Félix, A; Balzarini, J; Camarasa, M. J; Velázquez, S.

  Design and Discovery of a novel dipeptidil-peptidase IV (CD26)-based prodrug approach. J. Med. Chem. 2006, 49, 5339-5351.