Comment on The Ecstasy and Agony of Assay Interference Compounds.

Area of Science:

• Medicinal Chemistry
• Drug Discovery
• Computational Chemistry

Background:

• Assay screening frequently identifies false positives and compounds with undesirable mechanisms of action.
• Frequent-hitter behavior is circumstantial evidence, not definitive proof, of assay interference.
• Published Pan Assay INterference compoundS (PAINS) filters have limitations due to proprietary data scope.

Purpose of the Study:

• Critically examine an editorial on assay interference compounds.
• Clarify the distinction between false positives and undesirable compound activity.
• Evaluate the applicability and journal guidelines concerning Pan Assay INterference compoundS (PAINS) filters.

Main Methods:

• Critical analysis of published editorial and filter methodologies.
• Review of data scope and applicability of Pan Assay INterference compoundS (PAINS) filters.
• Examination of journal policies regarding compound activity data.

Main Results:

• False positives lack target interaction, while interference compounds act via undesirable mechanisms.
• Frequent-hitter status is not conclusive proof of assay interference.
• The applicability domain of Pan Assay INterference compoundS (PAINS) filters is restricted.

Conclusions:

• Journal guidelines should not differentiate assay results based on Pan Assay INterference compoundS (PAINS) filter matches.
• Using proprietary data in manuscript evaluation contradicts open science principles.
• A clear distinction between false positives and undesirable compound activity is essential for reliable drug discovery.