[Drug innovation and reverse thinking].

Area of Science:

• Pharmacology and Medicinal Chemistry
• Drug Discovery and Development

Background:

• Drug innovation is a complex, high-risk R&D process for new molecular entities.
• First-in-class drugs have dominated recent innovation, but follow-on drug launches have decreased.
• Conventional thinking in drug discovery often leads to similar drug categories, limiting novelty.

Purpose of the Study:

• To describe the strategy of inverse thinking as a feasible method for unique drug discovery.
• To explore how examining targets or effects from an opposite perspective can open new research routes.
• To illustrate the application of inverse thinking with specific drug examples.

Main Methods:

• Conceptual strategy development based on 'inverse thinking'.
• Analysis of existing drug discovery paradigms and their limitations.
• Case study illustrations of inverse thinking applied to specific drug classes.

Main Results:

• Inverse thinking provides a strategy to counteract inertial and conformity biases in drug discovery.
• This approach can lead to the identification of novel therapeutic targets and drug candidates.
• Examples demonstrate potential applications in developing opioid receptor antagonists, HSP90 activators, h ERG channel agonists, covalent drugs, and ultra-small drugs.

Conclusions:

• Inverse thinking is a viable strategy for achieving initiative and uniqueness in drug discovery.
• This approach offers a pathway to innovate beyond conventional methods, potentially reducing R&D risks.
• Further exploration of inverse thinking can unlock novel therapeutic avenues and drug classes.