How to Triage PAINS-Full Research.

Area of Science:

• Medicinal Chemistry
• Drug Discovery
• Assay Development

Background:

• Nonspecific bioactivity and assay artifacts are significant concerns in modern drug discovery.
• Pan assay interference compounds (PAINS) are chemical substructures known to cause promiscuous activity and assay interference.
• Despite awareness, research involving PAINS and PAINS-like compounds persists in publications.

Purpose of the Study:

• To explore the driving factors behind the continued publication of research involving PAINS.
• To provide insights for the early identification of PAINS and PAINS-like compounds.
• To prevent the propagation of costly and non-translatable research due to PAINS liabilities.

Main Methods:

• This perspective reviews existing literature and expert opinion on PAINS.
• It analyzes trends in scientific publications related to high-throughput screening (HTS) and medicinal chemistry.
• Factors contributing to the persistence of PAINS research are discussed.

Main Results:

• The continued publication of PAINS research is driven by several factors, including awareness gaps and publication pressures.
• Early recognition of PAINS is crucial to avoid misleading results in HTS campaigns.
• PAINS often lead to non-translatable findings, wasting significant resources.

Conclusions:

• Increased awareness and proactive identification strategies are needed to mitigate the impact of PAINS.
• Educating researchers on PAINS liabilities can prevent resource-intensive, non-productive research.
• Focusing on reliable compounds will accelerate the discovery of effective therapeutics.