Cisbio Bioassays’ IP-One Terbium Assay Enables Measurement of Different Compound Classes Using Single Technology
IP-One Tb is the first cell-based high throughput system that can easily detect inositol(1)phosphate (IP1), one of the major products of the phosphatidyl inositol cascade and which tightly correlates with Gq-coupled activity. Scientists at Roche in Basel, Switzerland chose IP-One Tb for the high-throughput profiling of confirmed hits from a primary screening. Due to the properties of terbium cryptate-based HTRF, high excitability, sensitivity, enhanced signal-to-noise ratio, low false-positive rate, and full reader compatibility, Roche found full and partial agonists, antagonists and neutral antagonists, and full and partial inverse agonists. Inverse agonists, in particular, have been difficult to study using existing assay technologies, such as calcium release.
“The excellent match of IP-One Tb’s terbium cryptate with the parallel readout of our reader allowed us to run several thousand curves with high data quality in only a few weeks,” said Michel Dietz, Roche Discovery Technologies, who led the project. “Its superior attributes enabled us to optimize our research in terms of time, cost, and results.”
Roche presented the results at the 2008 MipTec conference in Basel in a poster entitled “High Throughput Hit Profiling with the HTRF IP-One Terbium kit to determine Agonists, Inverse Agonists and Antagonists.” Roche’s poster won third prize in the conference poster competition out of over 100 entries from academic and industrial institutions, the highest poster prize awarded to an industrial entry.
Cisbio has long been a leader in the development of a comprehensive GPCR second messenger accumulation assay platform. With a terbium-based cAMP assay to complement IP-One Tb, Cisbio provides a terbium technological platform which investigators from pharmaceutical companies such as Roche can use to assess all GPCR targets. Inverse agonists, which block the natural function of a receptor, have been of particular interest to pharmaceutical researchers for two decades. Highly relevant in the development of pharmaceuticals which act on slow-acting receptors, inverse agonists are investigated for the treatment of central nervous system disorders.
About Cisbio Bioassays
Cisbio Bioassays is a global developer of products and technologies used in in vitro diagnostics and assay development for drug screening procedures. The company pioneered the field of homogenous fluorescence methodologies via its proprietary technology, HTRF®, a highly sensitive, robust technology for the detection of molecular interactions and widely used by the pharmaceutical industry for the high throughput screening stage of drug development. In addition, Cisbio produces a selection of biological reagents and methods used by pharmaceutical and biotechnology companies, as well as contract research organizations (CROs). Headquartered in Bagnols-sur-Cèze, France, with facilities in Bedford, MA, U.S.A. and a network of distributors worldwide, Cisbio is a member of the Belgium-based IBA group. IBA develops and markets leading edge technologies, pharmaceuticals and tailor-made solutions for healthcare with a focus on cancer diagnosis and therapy. Leveraging its scientific expertise, IBA is also active in the field of industrial sterilization and ionization. Listed on the pan-European stock exchange EURONEXT, IBA is included in the BelMid Index. Please visit www.htrf.com and www.iba-worldwide.com for more information about Cisbio and IBA.
About HTRF Terbium
HTRF is Cisbio Bioassays’ highly sensitive, robust technology for the detection of molecular interactions in vitro and is widely used for primary and secondary screening phases of drug development. HTRF combines standard FRET technology with time-resolved measurement of fluorescence and involves the use of specific fluorophores, the fruit of Prof. J.M. Lehn’s work, for which he was awarded a Nobel Prize for Chemistry in 1987. Launched in 2008, HTRF Terbium is Cisbio’s second generation HTRF technology and incorporates the Lumi4® terbium cryptate for enhanced sensitivity, assay window, and robustness without compromising the features and benefits that HTRF brings to assays: a “mix and measure” non-radioactive format, miniaturizable to uHTS formats, and showing excellent robustness and a low compound interference rate. HTRF Terbium allows for exceptional brightness and, unlike other terbium chelates, is stable in various biological media and its fluorescence is not affected by detergents, serum, divalent ions or chelating agents.
HTRF® is a registered trademark of Cisbio Bioassays.
Lumi4® is a registered trademark of Lumiphore, Inc.