Mechanism-based drugs, usually considered to be a conceptually distinct group from more mainstay non-covalent counterparts, have a strong track record as effective therapeutic agents. However, such agents are often disregarded when intiating a new drug discovery effort, largely due to concerns relating to potential safety liabilities. It is our view that the development of mechanism-based inhibitors of amine oxidase targets, specifically semicarbazide-sensitive amine oxidase (SSAO), provides an ideal opportunity to achieve long-lasting, complete inhibtion coupled with limited exposure. In turn, this inhibition translates to good efficacy in relevant disease models.
In this talk we will present the diverse challenges and obstacles associated with the development of this class of compound, with a particular focus on the optimisation of our molecules to "design out" substrate activity and "design in" selectivity over related amine oxidases.