Keynote review: In vitro safety pharmacology profiling: an essential tool for successful drug development

Whitebread, Steven; Hamon, Jacques; Bojanic, Dejan; Urbán, László

doi:10.1016/s1359-6446(05)03632-9

Cited by 369 publications

(283 citation statements)

References 47 publications

Supporting

Mentioning

263

Contrasting

Unclassified

Order By: Relevance

“…Although some of the more general considerations involved in target selection are discussed here, several recent publications are available that provide additional rationale for target selection under specific circumstances [3][4][5][6][7][8][9][10] .…”

Section: Discussionmentioning

confidence: 99%

Secondary pharmacology data to assess potential off-target activity of new drugs: a regulatory perspective

Papoian

Chiu

Elayan

et al. 2015

Nat Rev Drug Discov

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Secondary pharmacology data to assess potential off-target activity of new drugs: a regulatory perspective

Papoian

Chiu

Elayan

et al. 2015

Nat Rev Drug Discov

View full text Add to dashboard Cite

“…28 This panel includes molecular targets from diverse classes known to be associated with adverse clinical events (hERG, 5-HT 2B , PDE3, etc. ), as well as targets of interest to DMPK such as drug transporters and also phenotypic surrogate assays of toxicity.…”

Section: Discussionmentioning

confidence: 99%

The BlueScreen-384 Assay as an Indicator of Genotoxic Hazard Potential in Early-Stage Drug Discovery

et al. 2013

View full text Add to dashboard Cite

High-throughput cell-based techniques that permit early detection of compound-induced genotoxic damage have recently become available. Methods based on induction of the GADD45a promoter are attractive because multiple intracellular mechanisms that detect genetic damage intersect at this checkpoint gene. Consequently, assays such as GreenScreen HC, which uses p53-competant human TK6 lymphoblastoid cells and a GADD45a-GFP reporter, have been developed. GreenScreen HC allows weekly testing of dozens of compounds using 96-well microplates, with high interassay consistency. BlueScreen HC is a recent advancement, coupling GADD45a to Gaussia luciferase, with several advantages over GADD45a-GFP including the potential for miniaturization. Here we describe implementation of a 384-well BlueScreen assay. For drug discovery programs carrying out iterative analogue synthesis around a chemical lead series, these assays permit assessment of compound genotoxic potential in parallel to, rather than subsequent to, determination of activity at a therapeutic target. We demonstrate comparability of BlueScreen-384 to GreenScreen HC and illustrate the use of BlueScreen-384 to explore the structure-activity relationship around a genotoxic lead molecule to identify nongenotoxic analogues. BlueScreen-384 can reduce the need for costly and time-consuming analogue testing in more traditional genotoxicity tests, such as the Ames test.

show abstract

“…The biochemical validation of hypothesized drug-target interactions is laborious, time-consuming and expensive [31] [49]. Therefore, computational methods have been proposed for the prediction of drug-target interactions [5] [22] [23] [34].…”

Section: Introductionmentioning

confidence: 99%

Drug–target interaction prediction with Bipartite Local Models and hubness-aware regression

Búza

Peška

2017

Neurocomputing

View full text Add to dashboard Cite

Keynote review: In vitro safety pharmacology profiling: an essential tool for successful drug development

Cited by 369 publications

References 47 publications

Secondary pharmacology data to assess potential off-target activity of new drugs: a regulatory perspective

Secondary pharmacology data to assess potential off-target activity of new drugs: a regulatory perspective

The BlueScreen-384 Assay as an Indicator of Genotoxic Hazard Potential in Early-Stage Drug Discovery

Drug–target interaction prediction with Bipartite Local Models and hubness-aware regression

Contact Info

Product

Resources

About