Pan-assay interference compounds

Pan-assay interference compounds (PAINS)

Illustration of common PAINS structures.

Pan-assay interference compounds, commonly abbreviated as PAINS, are chemical compounds that often give false positive results in high-throughput screening (HTS) assays. These compounds interfere with multiple assay technologies, leading to misleading results in drug discovery processes. Understanding and identifying PAINS is crucial for researchers in the field of medicinal chemistry and pharmacology.

Characteristics of PAINS

PAINS are characterized by their ability to interact with multiple targets or assay components in a non-specific manner. This can occur through various mechanisms, such as:

• Reactive functional groups: Some PAINS contain reactive groups that can form covalent bonds with proteins or other assay components.
• Redox activity: Compounds that undergo redox reactions can interfere with assays that rely on redox-sensitive readouts.
• Chelation: PAINS may chelate metal ions that are essential for the function of certain proteins or enzymes.
• Fluorescence interference: Some PAINS are inherently fluorescent or can quench fluorescence, affecting assays that use fluorescence-based detection methods.

Identification and Avoidance

Examples of PAINS structures.

To identify PAINS, researchers use computational filters and databases that catalog known PAINS structures. These tools help in screening out compounds that are likely to cause assay interference. Some common strategies to avoid PAINS include:

• Using PAINS filters: Software tools that flag potential PAINS based on their chemical structure.
• Cross-validation: Testing compounds in multiple assay formats to confirm their activity is not due to interference.
• Structural analysis: Examining the chemical structure for known PAINS motifs.

Impact on Drug Discovery

PAINS can significantly impact the drug discovery process by leading researchers to pursue false leads. This can result in wasted resources and time. By identifying and excluding PAINS early in the screening process, researchers can focus on more promising compounds, improving the efficiency of drug development.

Related pages

• High-throughput screening
• Medicinal chemistry
• Pharmacology
• Drug discovery