Selecting a preclinical candidate is a critical step in drug development. It is a million dollars decision. It involves choosing the most promising drug molecule from a pool of candidates to move forward for further testing. Obviously, the selection process is complicated and requires years of experiences and intelligence. For beginners in this field, the below breakdown of a strategic approach for selecting a preclinical candidate should be good starting point.
1. Evaluate In Vitro Data:
Analyze data from cell-based assays to assess a candidate’s ability to interact with the target molecule and produce the desired biological effect.
Consider factors like potency (concentration needed for a response), efficacy (strength of the effect), and selectivity (ability to target the specific molecule without affecting others).
2. Assess ADME Properties:
Absorption, Distribution, Metabolism, and Excretion (ADME) properties significantly impact a drug’s effectiveness and safety.
Evaluate factors like how well the drug is absorbed from the site of administration, how it distributes throughout the body, how it’s metabolized by the body, and how it’s eliminated.
Ideal candidates demonstrate good oral bioavailability (absorption through the digestive system) and a long enough half-life (time it takes for the drug concentration to decrease by half) to be effective.
3. Prioritize Drug Safety:
Safety is paramount. Analyze in vitro data for potential off-target effects and cytotoxicity (toxic to cells).
Favor candidates with minimal off-target effects and low cytotoxicity.
4. Consider Manufacturability:
Choose a candidate that can be synthesized or manufactured cost-effectively and at a commercially viable scale.
Complex or expensive manufacturing processes can hinder drug development.
5. In Vivo Testing and Lead Optimization:
Once promising candidates are identified based on in vitro data, ADME properties, and safety considerations, in vivo testing in animal models can begin.
These studies provide valuable insights into the drug’s efficacy, pharmacokinetics (movement of the drug through the body), and potential toxicities in a whole organism.
Based on in vivo data, further optimization of the lead candidate’s structure can be performed to improve its properties.
6. Selection Criteria Integration:
No single criterion is absolute. The selection process involves weighing in vitro data, ADME properties, safety profile, manufacturability, and in vivo testing results.
7. Prioritization and Decision Making:
Based on the integrated analysis of all selection criteria, prioritize the most promising candidates.
Consider factors like the severity of the targeted disease, potential market size, and the overall risk-benefit profile of the candidate.
8. Expert Input and Collaboration:
Throughout the selection process, involve scientists with expertise in medicinal chemistry, pharmacology, toxicology, and drug development.
Their diverse perspectives can enhance the selection process.
By following a well-defined strategy that considers in vitro data, ADME properties, safety, manufacturability, and in vivo testing results, you can increase your chances of selecting a preclinical candidate with the greatest potential for success in further development.
In addition, it is critical to maintain a clear and documented rationale for selecting a preclinical candidate. Ensure every decision is scientifically evidence-supported. However, it is still necessary to be prepared to adapt your selection strategy as new data emerges during the development process. Selecting a preclinical candidate is an iterative process. As you gather more information, you may need to refine your selection criteria and re-evaluate your candidate pool.