HTS instrument discovers low affinity inhibitors of the Inositol Phosphate (IP) signaling pathway

EJ Dell (1), JL Tardieu (2), F Degorce (2) (1) BMG LABTECH, (2) Cisbio 02/2012

G-protein coupled receptors (GPCRs) are transmembrane proteins which play a key role in the signal transduction of extracellular stimuli. This occurs by the production of second messenger such as inositol 1,4,5-triphosphate (IP3). However, IP3's very short half-life makes its assessment challenging for drug screening assays. Alternatively, accumulation of the downstream metabolite inositol monophosphate (IP1) can be monitored.


The IP-One HTRF® assay uses a monoclonal antibody that recognizes IP1 and it is based on a competition format in which the intracellular accumulation of IP1 inhibits the fluorescence resonance energy transfer (FRET) signal between the HTRF® donor and acceptor. An IP1 calibration curve estimates the IP1 concentration accumulated in cells as a function of the compound concentration.


The IP-One HTRF® assay from Cisbio was performed on the next-generation high-throuhput screening reader, the PHERAstar® FS from BMG LABTECH. It discovered low-affinity compounds that were not identified with an HTS CCD camera-based microplate reader.

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