s The Discovery of CDP323, a Potent Alpha4 Integrin Antagonist

Blocking the action of alpha4 integrin would be expected to be of therapeutic benefit in the management of autoimmune diseases. Although this has been successfully demonstrated in the clinic with a monoclonal antibody for the treatment of multiple sclerosis, there are no small molecule alpha4 integrin antagonists on the market despite significant endeavour over the last 15-20 years. We review our efforts in this area, starting from a cyclic peptide based on an integrin recognition sequence and culminating in the low molecular weight clinical candidate, CDP323. We include a discussion on pre-clinical pharmacological data for CDP323.