A small Korean biotechnology company has scored a first with the identification of the binding site for phosphodiesterase-5, the enzyme targeted by Pfizer's Viagra (sildenafil) and other drugs for the treatment of erectile dysfunction.
CrystalGenomics hopes that the publication of its work, in Nature, will help it secure its first major pharmaceutical collaboration. The characterisation of the binding site should aid in the development of a new generation of PDE-5 inhibitors with reduced side effects.
The researchers describe the three-dimensional structures of the catalytic domain of human PDE-5 complexed with all three of the licenced selective inhibitors i.e. sildenafil, Lilly ICOS' Cialis (tadalafil) and GlaxoSmithKline and Bayer's Levitra (vardenafil).
These compounds have been designed to be as selective as possible, with minimal interaction with other PDE enzymes. Nevertheless, they are associated with some side effects, notably flushing, blurred vision, headaches and dizziness.
CrystalGenomics has a suite of technologies - known as SPS, SCP and SDF that are targeted towards uncovering the 3-D structure of disease-related proteins. The company has access to a third-generation synchrotron in Pohang, which enables it to determine various target protein structures, and is currently optimising various leads targeting the proteins related to diabetes, cancer and infectious diseases.