Multidrug resistance is a particular limitation to medical treatment of diseases related to the major causes of mortality globally, e.g. chemotherapy, antibiotic treatment and HIV medication. The project involves basic research on ABC transporters involve d in multidrug resistance combining theoretical molecular modelling and experimental pharmacology. Sildenafil (Viagra) is an inhibitor of ABCC5 drug efflux, as well as an inhibitor of phosphodiesterase 5 (PDE5). Dr. Aina Westrheim Ravna has previously spe nt 6 weeks in the spring semester of 2009 performing virtual ligand screening for
sildenafil derivates into an ABCC5 model at Ruben Abagyan's lab (Molsoft/The Scripps Research Institute, La Jolla, USA), and she will spend 3 additional months at Ruben Abag yan's lab, which recently moved from The Scripps Research Institute to The Skaggs School of Pharmacy & Pharmaceutical Sciences at The University of California, La Jolla, USA, to perform further virtual ligand screening studies. The compounds identified as potential ABCC5 inhibitors will be tested for affinity to ABCC5 and PDE5 in vitro at the University of Tromsø, in order to reveal potential therapeutics that can inhibit ABCC5 mediated drug efflux without producing side-effects (used therapeutically in e rectile dysfunction) caused by PDE5-inhibition (smooth muscle relaxation (vasodilation)).