Part 1 – Discovery
May is our month to review how new medicines are developed. This will be an eight part series describing the different stages of drug development which are applicable in all regulatory jurisdictions.
The aim of discovery research is to clearly identify the hypothetical mechanisms for the target disease state, develop relevant mechanistic models for testing potential therapeutics, and find active drugs (either chemical or biological) in the model. This is the most challenging part of pharmaceutical research. The proposed mechanism for drug action must be understood well enough to create a model system which demonstrates a direct connection between the presence of a drug and a relevant change in the system. This system change is often referred to as the target, and increased confidence in a target is established when multiple model systems (for example, published studies supporting the mechanism, cell lines expressing a receptor, animal models, or measurable genetic variants) support the mechanism. Once a target has been defined, active drugs must be found by various screening methods (sampling in an existing compound library, computer modeling of the molecular target, or brute force measurements of many compound structures) which frequently evaluate thousands of individual compounds before finding a ‘hit’ which shows the desired activity in the target. Many programs fail to find a hit with sufficient activity for development and unique enough to permit filing a patent even after screening thousands of compounds. When a hit is found, analog compounds are created and screened to find a lead compound and at least one backup acceptable for preclinical development. Compounds are also frequently screened in parallel for properties that are known to make them easier to develop as a medicine. These often referred to as ‘druggable’ properties.
Readers interested in more detail will find this 2011 review article published by Hughes et al. in the British Journal of Pharmacology presents an accessible explanation of the preclinical discovery process. Next up in this series – Preclinical Development!
Reach out to me if you want to know more or discuss your medical product development challenges.
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Text Copyright © 2020 Katrina Rogers
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