Composing compound libraries for hit discovery--rationality-driven preselection or random choice by structural...

Area of Science:

• Medicinal Chemistry
• Biochemistry
• Drug Discovery

Background:

• Surface plasmon resonance (SPR) is crucial for screening compound libraries to identify drug scaffolds.
• Traditional SPR screening often suffers from low hit rates and is time-consuming.
• Developing efficient methods to improve hit rates and reduce library size is essential for drug discovery.

Purpose of the Study:

• To evaluate the effectiveness of different compound selection strategies for identifying inhibitors of PqsD.
• To compare target-specific preselection methods with traditional fragment library screening.
• To determine if preselection improves hit rates and reduces screening time.

Main Methods:

• Investigated three strategies for identifying PqsD inhibitors using SPR.
• Employed target-specific preselection based on homologous protein inhibition and virtual screening predictions.
• Screened a diverse fragment library as a comparative baseline.

Main Results:

• Methods utilizing preselected compound libraries demonstrated higher hit rates compared to standard screening.
• Target-oriented compound selection proved to be a more time-effective approach.
• Virtual screening and homologous protein inhibition aided in identifying potent inhibitors.

Conclusions:

• Preselection of compounds based on target-specific information enhances SPR screening efficiency.
• Target-oriented compound selection offers a time-effective alternative for drug discovery.
• Optimized screening strategies are vital for accelerating the identification of novel drug scaffolds.