15-minute Facts: Multi-parameter optimization – friend or foe?

Continuing our series of 15-minute webinars, Head of Medicinal Chemistry, Tom Pesnot, takes us on journey into the world of multi-parameter optimization (MPO) in drug discovery.

What is multi-parameter optimization?

Developing safe and efficacious drugs requires the careful balance of multiple properties, including potency, absorption, distribution, metabolism, elimination, and safety properties. Balancing these, often conflicting, design goals while dealing with the huge volume of complex data generated in drug discovery makes it very difficult to optimize all of these parameters without computational support.

MPO is now a widely used computational tool that has become indispensable to medicinal chemists. With the right MPO predictor selected and effectively implemented you can significantly reduce the time it takes to deliver a candidate molecule. After all, MPO simply delivers a quantitative version of the predictions medicinal chemists routinely make during the design process; but it does it more quickly and it eliminates the ‘cognitive’ biases that even the best scientists can succumb to when dealing large volumes of complex data. What’s more, these predictive MPO models are easy to implement and incorporate into computational workflows to support the design process.

Although a few MPO scoring systems, such as the CNS-MPO, have been widely adopted by the drug discovery community, alternative MPO methodologies can be conceived and implemented. This raises many questions for medicinal chemistry managers such as:

• Which MPO should I use?
• At what stage?
• Is the selected MPO relevant to the therapeutic intervention?
• How should I calculate the parameters?
• How can I use this information to guide drug design?