Drug Discovery is the research process by which pharmaceutical and biopharmaceutical companies discover and design drugs for unmet, or inadequately met, medical needs. The drug discovery process starts with the identification of a suitable drug targets, generally naturally existing compounds, or compounds involved in the pathology of interest. Analytical Development is needed to perform Method Scouting activities, to develop High-throughput screening (HTS) processes to identify new drugs for a particular disease, using large libraries of chemicals. For example if the target is a protein kinase, a range of chemicals will be tested for their ability to inhibit kinase (or its kinase activity).
Drug Discovery Screening
High-throughput screening determines the selectivity of compound targets which ideally only interfere with the chosen target, and not other related targets. Cross screening runs take place to see whether the “hits” against the chosen target will interfere with other related targets. If a compound “hits” unrelated targets it is likely off-target toxicity will occur at the clinical testing stage. The output of early screening runs is very rarely a perfect drug candidate, but typically the identification of several compounds with some degree of activity, if these compounds share common chemical features, and one or more pharmacophores can then be developed.
Following screening medicinal chemists use structure-activity relationships (SARs) to improve certain features of the lead compound in terms of increased activity against the chosen target, reduce activity against unrelated targets, and improved drug likeness, or ADME properties, of the molecule. This process usually occurs through several iterative screening runs, and leads to an improvement in the properties of the new molecular entities.
The next step is the favoured compounds to go to in-vitro and in-vivo testing, for activity in the disease model of choice. This enables:
• synthesis of the lead compounds
• new analogs with improved potency
• reduced off-target activities
• physiochemical / metabolic properties suggestive of reasonable in-vivo pharmacokinetics
Optimisation occurs through chemical modification, modifications through structure-activity analysis (SAR), and structure-based design.
Drug discovery requires Process Development to allow scale-up and Technology Transfer at a later date, and project management to help keep the process on budget and within time-frame, in line with commercial objectives. The process is broadly split into three main areas:-
1. Discovery to Development Track
The drug discovery to development process is used by pharmaceutical companies to identify a Target Product Profile (TPP). This establishes important clinical attributes, drives clinical plans, reflects anticipated label, drives company portfolio value and ranking, and guides decision-making.
2. Non-Clinical Development
Non-clinical development involves non-clinical safety evaluations, appropriate safety profiles to be developed, targets to be identified, methods identification for monitoring toxicity and blood drug levels in clinic, type of toxicity observed in preclinical models (predictive of toxicity in patients), adequate exposure and safety margins for patient population and indication involved.
3. Clinical Development
The final stage of drug discovery is the clinical development. This requires Clinical Trials, regulatory filings, agency meetings and approval of all documentation obtained during the course of the drug discovery to development process. This is necessary to establish product quality, safety and efficacy.
How Woodley BioReg can help support Drug Discovery
WBR can support drug discovery and development process through;
• Non-clinical development support
• Clinical development support and Trials management
• Non-clinical/Clinical clerk Interpretation
• Non-clinical/Clinical Assessments
For more information, help and advice on Drug Discovery please contact us.