Drug discovery process

• Drug development is a timely, cumbersome, and expensive process. It takes about 14+ years to carry out investigations and clinical trials. The phases of drug development can be split into pre discovery, drug discovery, and development.
• The first step in the drug discovery process involves identifying potential targets that are involved in disease pathology. This can be achieved through literature analysis. Finding out what is already out their about the disease to identify potential targets
• Target identification is based on knowledge from basic research studies such as genetics, molecular biology, cellular biochemistry, immunology, etc. This information helps identify proteins or other molecules that play an important role in the disease state.
• Once a target is identified, computational methods (cavity searching, protein-binding predictions) are used to identify if the target is suitable for drug targetting

  
  

  (i.e., if there is a way to modulate its activity).
• Step 3 involves identifying a lead that can bind to your target protein successfully. After a lead has been identified it is important to optimise its effects, by altering its structure to change its efficacy and tolerability. Chemists modify the structures of the hits to increase their potency and selectivity to protein X, turning them into lead compounds
• Pre-clinical trials involving in-vitro and in-vivo experiements to assess the pharmacodynamics and pharmacokinetics of the drug. To observe the safety and tolerability in living organisms
• Human trials:

  Phase 1: this is done in healthy volunteers (100 people), to confirm safety in humans

  Phase 2: done in a larger cohort (100-300), efficacy, safety and delivery method
• Phase 3: large scale clinical trial with thousands of patients, to test long term side effects and effectiveness
• Phase 4: post marketing surveillance, monitoring adverse events and collecting data about the drugs use in real world settings
• Phase 4 trials to observe the long-term effects even after the drug has been approved. Pharmacovigilance and also trials to reconfirm the efficacy of the drug
• Drug development costs vary widely depending on the type of disease being targeted, but estimates suggest that it takes around $2 billion and 15 years to bring a single drug to market
• A drug may be withdrawn from the market due to serious side effects or lack of efficacy
• How do we identify hit compounds?

  High throughput screening tests large libraries of chemical compounds for potential lead compounds.

  Docking to predict the lead-protein complex
• HTS enables rapid testing of thousands of compounds to identify those with desirable biological activities.
• Pharmacore remodeling and QSAR are utilised to predict the toxicity of the compound and especially the pharma-core, which is responsible for the activity of the lead compound to help optimise it.
• Once lead compounds have been identified, the compounds are then optimised to improve their potency, selectivity, and safety properties. in vitro analysis is used to asses the ADME properties of the lead compounds