PuSH - Publication Server of Helmholtz Zentrum München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Schorpp, K.K. ; Rothenaigner, I. ; Salmina, E. ; Reinshagen, J.* ; Low, T.* ; Brenke, J.K. ; Gopalakrishnan, J.* ; Tetko, I.V. ; Gul, S.* ; Hadian, K.

Identification of small-molecule frequent hitters from AlphaScreen high-throughput screens.

J. Biomol. Screen. 19, 715-726 (2013)
Publ. Version/Full Text Volltext DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Although small-molecule drug discovery efforts have focused largely on enzyme, receptor, and ion-channel targets, there has been an increase in such activities to search for protein-protein interaction (PPI) disruptors by applying high-throughout screening (HTS)-compatible protein-binding assays. However, a disadvantage of these assays is that many primary hits are frequent hitters regardless of the PPI being investigated. We have used the AlphaScreen technology to screen four different robust PPI assays each against 25,000 compounds. These activities led to the identification of 137 compounds that demonstrated repeated activity in all PPI assays. These compounds were subsequently evaluated in two AlphaScreen counter assays, leading to classification of compounds that either interfered with the AlphaScreen chemistry (60 compounds) or prevented the binding of the protein His-tag moiety to nickel chelate (Ni(2+)-NTA) beads of the AlphaScreen detection system (77 compounds). To further triage the 137 frequent hitters, we subsequently confirmed by a time-resolved fluorescence resonance energy transfer assay that most of these compounds were only frequent hitters in AlphaScreen assays. A chemoinformatics analysis of the apparent hits provided details of the compounds that can be flagged as frequent hitters of the AlphaScreen technology, and these data have broad applicability for users of these detection technologies.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
2.207
0.656
65
74
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords Alphascreen ; Protein-protein Interaction ; Assay Development ; Frequent Hitter ; Drug Discovery ; High-throughput Screening; Protein-protein Interactions; Drug Discovery; Solubility; Chemistry; Libraries; Fragment; Filters; Models; Domain
Language english
Publication Year 2013
HGF-reported in Year 2014
ISSN (print) / ISBN 1087-0571
e-ISSN 1552-454X
Journal Journal of Biomolecular Screening
Quellenangaben Volume: 19, Issue: 5, Pages: 715-726 Article Number: , Supplement: ,
Publisher Sage
Publishing Place Thousand Oaks
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Toxicology and Pharmacology (TOX)
Institute of Structural Biology (STB)
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-505293-001
G-503000-003
PubMed ID 24371213
DOI 10.1177/1087057113516861
WOS ID WOS:000340210300011
Scopus ID 84900455031
Erfassungsdatum 2014-01-27
[➜Report correction]