Preclinical Development (Small Molecules)

Millions of compounds may have been tested in the original screen, followed by as many as 500 compounds synthesised in the subsequent optimisation, leading to only 10-20 compounds being tested in advanced models of disease and finally, only 1-2 compounds selected for testing in humans.

Those final candidate molecules need to meet certain properties before considered as suitable for testing in humans.

• Chemical properties: the compound should be stable and synthesis of the compound is straight forward so that it is easily scalable.
• Physicochemical properties: the compounds should be soluble and preferably meet the Lipinski ‘Rule of 5’.
• Pharmacological properties: the compound should show selectivity towards the target and bind to the target, in both the in vitro experiments and the in vivo experiments (animal models).
• Pharmacokinetic properties: the compounds should be bioavailable, display appropriate half-life and the correct distribution in animals. The mode of action of the compound should be well known.
• Safety and toxicity potential: the compound should not show toxicity, such as cardiac toxicity, genotoxicity, and hepatotoxicity, in both in vitro or in vivo experiments.

When a compound passes all the necessary procedures, this compound undergoes Pharmaceutical formulation, which is the process where an active compound is combined with different chemical and/ or biochemical substances to produce the final medicinal product.