- Based at Department of Chemistry
Statins are amongst the most commonly prescribed drugs across the world, being routinely taken by millions of patients. These drugs inhibit the human enzyme responsible for cholesterol synthesis, and are associated with reduced frequency of strokes and myocardial infarction.
Despite their huge success, many patients taking statins frequently report suffering muscular pain and weakness and, in rare cases, rhabdomyolysis which can be fatal. The Sitsapesan group have found that simvastatin, a commonly used statin, and cerivastatin, a drug removed from the market due to rhabdomyolysis, both increase the opening of skeletal ryanodine receptor (RyR1) channels, an effect likely to contribute to statin-induced muscle myopathy and rhabdomyolysis.
I am working on a joint project with Angela Russell (Dept. of Chemistry) to study how statins interact with RyR channels. Our goal is to use computational modelling along with modern synthetic and medicinal chemistry techniques to design new potential statin molecules which do not alter RyR1 channel function and produce fewer side effects.
Venturi E. et al, (2018), Br J Pharmacol, 175, 938 - 952
Statins Bind to Cardiac Ryanodine Receptor (RyR2) Channels to Alter Opening Frequency
Wilson AD. et al, (2018), BIOPHYSICAL JOURNAL, 114, 621A - 622A