This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (16) Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Lundholt, B. K. Articles by Nielsen, S. J. Search for Related Content PubMed PubMed Citation Articles by Lundholt, B. K. Articles by Nielsen, S. J. Social Bookmarking                         What's this?

Identification of Akt Pathway Inhibitors Using Redistribution Screening on the FLIPR and the IN Cell 3000 Analyzer

BioImage A/S, Copenhagen, Denmark

Viggo Linde

BioImage A/S, Copenhagen, Denmark

Frosty Loechel

BioImage A/S, Copenhagen, Denmark

Hans-Christian Pedersen

BioImage A/S, Copenhagen, Denmark

Søren Møller

BioImage A/S, Copenhagen, Denmark

Morten Præstegaard

BioImage A/S, Copenhagen, Denmark

Ivan Mikkelsen

BioImage A/S, Copenhagen, Denmark

Kurt Scudder

BioImage A/S, Copenhagen, Denmark

Sara Petersen Bjørn

BioImage A/S, Copenhagen, Denmark

Morten Heide

BioImage A/S, Copenhagen, Denmark

Per O. G. Arkhammar

BioImage A/S, Copenhagen, Denmark and Novo Nordisk A/S, Måløv, Denmark

Robert Terry

BioImage A/S, Copenhagen, Denmark

Søren Jensby Nielsen

BioImage A/S, Copenhagen, Denmark

The PI3-kinase/Akt pathway is an important cell survival pathway that is deregulated in the majority of human cancers. Despite the apparent druggability of several kinases in the pathway, no specific catalytic inhibitors have been reported in the literature. The authors describe the development of a fluorometric imaging plate reader (FLIPR)-based Akt1 translocation assay to discover inhibitors of Akt1 activation. Screening of a diverse chemical library of 45,000 compounds resulted in identification of several classes of Akt1 translocation inhibitors. Using a combination of classical in vitro assays and translocation assays directed at different steps of the Akt pathway, the mechanisms of action of 2 selected chemical classes were further defined. Protein translocation assays emerge as powerful tools for hit identification and characterization. (Journal of Biomolecular Screening 2005:20-29)

Key Words: FLIPR • PI3-kinase/Akt pathway • protein translocation assays • high-throughput screening • Redistribution screening

Journal of Biomolecular Screening, Vol. 10, No. 1, 20-29 (2005)
DOI: 10.1177/1087057104269989


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				V. Unterreiner, Y. Ibig-Rehm, M. Simonen, H. Gubler, and D. Gabriel Comparison of Variability and Sensitivity between Nuclear Translocation and Luciferase Reporter Gene Assays J Biomol Screen, January 1, 2009; 14(1): 59 - 65. [Abstract] [PDF]

				C. Granas, B. K. Lundholt, F. Loechel, H.-C. Pedersen, S. P. Bjorn, V. Linde, C. Krogh-Jensen, E.-M. D. Nielsen, M. Praestegaard, and S. J. Nielsen Identification of RAS-Mitogen-Activated Protein Kinase Signaling Pathway Modulators in an ERF1 Redistribution(R) Screen J Biomol Screen, June 1, 2006; 11(4): 423 - 434. [Abstract] [PDF]