Drug discovery and development: lessons from an undeveloped drug

Area of Science:

• Pharmacology and Pharmaceutical Sciences
• Drug Discovery and Development

Background:

• Current pharmaceutical industry practices for drug discovery and preclinical development are examined.
• The antimalarial drug artemisinin serves as a case study for a potentially overlooked therapeutic agent.
• Artemisinin is a safe and effective treatment for a life-threatening disease, despite its characteristics making it unlikely for modern development.

Purpose of the Study:

• To critique the efficacy of prespecified charts and undesired property lists in molecule deselection.
• To propose advanced modeling techniques for improved drug candidate selection.
• To enhance the probability of successful drug development and market entry for best-in-class medications.

Main Methods:

• Discussion of current drug discovery and preclinical development paradigms.
• Analysis of the artemisinin case study.
• Proposal for the implementation of systems pharmacology, disease progression, and pharmacokinetic/pharmacodynamic (PK/PD) models.

Main Results:

• Prespecified deselection criteria may lead to the exclusion of valuable drug candidates.
• Systems pharmacology and PK/PD models provide a more robust framework for evaluating drug potential.
• These models offer a superior approach to identifying candidates with a higher likelihood of market success.

Conclusions:

• Rethinking rigid deselection strategies is crucial for uncovering innovative therapies.
• Adoption of systems pharmacology and integrated modeling approaches can optimize drug candidate selection.
• This strategic shift promises to increase the successful development of vital medications for patients.