Pan-assay interference compounds: Difference between revisions

Latest revision as of 16:27, 16 February 2025

Pan-assay interference compounds (PAINS)[edit]

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[edit]

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[edit]

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[edit]

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[edit]

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-'''Pan-assay interference compounds''' (often abbreviated as '''PAINS''') are a class of [[chemical compounds]] that are often false positives in [[high-throughput screening]] (HTS) of [[chemical libraries]] for identification of active compounds in [[drug discovery]].
+== Pan-assay interference compounds (PAINS) ==
-== Overview ==
+[[File:PAINS_Figure.tif|thumb|right|Illustration of common PAINS structures.]]
-PAINS are compounds that interfere with the assay detection system or form reactive compounds under the assay conditions, leading to false positive results. They are a major concern in drug discovery as they can lead to wasted time and resources in following up on these false leads.
+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]].
-== Identification ==
+== Characteristics of PAINS ==
-PAINS can be identified through various methods, including [[chemoinformatics]] approaches that use [[machine learning]] algorithms to predict PAINS based on their chemical structure. Other methods include experimental approaches such as counter-screening and orthogonal assays.
+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:
-== Impact on Drug Discovery ==
+* '''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 ==
+[[File:PAINS_Figure.tif|thumb|left|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:
-The impact of PAINS on drug discovery is significant. They can lead to false leads, wasting valuable time and resources. Furthermore, they can also lead to incorrect conclusions about the mechanism of action of a potential drug, leading to further wasted resources in the development process.
+* '''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.
-== Mitigation Strategies ==
+== Impact on Drug Discovery ==
-Several strategies can be employed to mitigate the impact of PAINS on drug discovery. These include the use of more selective assays, counter-screening, and the use of predictive models to identify potential PAINS before they are tested in assays.
+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.
-== See Also ==
+== Related pages ==
+* [[High-throughput screening]]
+* [[Medicinal chemistry]]
+* [[Pharmacology]]
 * [[Drug discovery]]
-* [[High-throughput screening]]
-* [[Chemoinformatics]]
-* [[Machine learning in drug discovery]]
-== References ==
-<references />
+{{Drug discovery}}
+[[Category:Medicinal chemistry]]
 [[Category:Pharmacology]]
-[[Category:Drug discovery]]
-[[Category:Chemoinformatics]]
-{{pharmacology-stub}}