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X-ray Structures of Target-Ligand Complexes Containing Compounds with Assay Interference Potential.

Abstract：

:Pan assay interference compounds (PAINS) have become a paradigm for compound classes that might cause artifacts in biological assays. PAINS-defining substructures are typically contained in larger compounds. We have systematically examined X-ray structures of protein-ligand complexes for compounds containing PAINS motifs. In 2874 X-ray structures, 1107 unique ligands with PAINS substructures belonging to 70 different classes were identified. PAINS most frequently detected in crystallographic ligands included a number of prominent candidates such as quinones, catechols, or Mannich bases. However, on the basis of X-ray data, the presence of specific ligand-target interactions and reactivity under assay conditions were not mutually exclusive. In some instances, reactivity of ligands was likely responsible for complex formation. Different categories of PAINS-containing ligands were distinguished, which aided in the interpretation of specific interactions versus potential assay artifacts. Careful consideration of structural data adds another dimension to the analysis of interference compounds.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Gilberg E,Gütschow M,Bajorath J

doi

10.1021/acs.jmedchem.7b01780

subject

Has Abstract

pub_date

2018-02-08 00:00:00

pages

1276-1284

issue

3

eissn

0022-2623

issn

1520-4804

journal_volume

61

pub_type

杂志文章

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