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Dimerix HIT Assay to Understand Receptor Interactions Applied to Kinase Targets

Published: Friday, May 31, 2013
Last Updated: Thursday, May 30, 2013
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Better understanding of receptor signalling, including effects arising from their functional interaction in heteromeric complexes, will progress drug development. Dimerix’s HIT assay is used to understand kinase heteromer signalling pathways.

Patents have now been granted for Dimerix’s Heteromer Investigation Technology (HIT) assay in the US, Europe, China and Australia, with applications pending in other jurisdictions.  Dimerix’s HIT assay enables a ligand responsive interrogation of a wide range of signalling pathways that can be triggered by a complex of at least two receptors (or proteins).  The assay can be utilised in high-throughput screening to obtain novel hits against the heteromer target and its components, or employed to better profile existing leads for signalling elicited through heteromer formation.  The broad application of Dimerix’s technology enables it to be licensed for a range of proximity-based reporter systems enabling optimal information and outcomes.

Most recently, an application of Dimerix’s assay to kinase heteromers has been reported.  A/Prof Kevin Pfleger, co-inventor of Dimerix’s assay technology, is senior author of a paper entitled ‘Profiling Epidermal Growth Factor Receptor and Heregulin Receptor Heteromerization Using Receptor Tyrosine Kinase Heteromer Investigation Technology’ published 20 May 2013 in PLOS ONE.

The study demonstrates the use of Dimerix’s HIT assay to investigate the heteromeric complexes formed by EGFR and HER3 receptors, and the effect on the Grb2 signalling pathway.  The data show that heteromerization of the receptors is required for HER3 to interact with Grb2, including evidence that this occurs via a transactivation mechanism.

Why is this important?  These kinase receptors are known to be involved in various human cancers.  Better understanding of receptor signalling, including effects arising from their functional interaction in heteromeric complexes, will progress drug development.  Indeed, the importance of EGFR-HER3 heteromerization has been demonstrated by other studies showing a beneficial effect of dual-action antibodies targeting both receptors. 

Dimerix’s assay not only provides a useful tool for interrogating heteromer signalling, but can also be used for high-throughput screening to identify hits against the heteromer as well as respective monomers.  In collaborative work with partners, Dimerix has enabled profiling and screening activities encompassing a range of proteins and signalling pathways.  Dimerix has strong expertise in the area of GPCRs and their various G-protein or beta-arrestin signalling pathways, including GPCR deorphanisation.

Dimerix’s internal research has used its assay in a core research program to develop an improved therapy for reduction of proteinuria in chronic kidney disease. Proteinuria is an indicator of ongoing kidney damage.

More information is available on Dimerix’s website: www.dimerix.com. To see a schematic of Dimerix’s assay for different reporter systems, please go to the Dimerix Platform section of our website.


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