QUEST -- A new paradigm for small-molecule drug discovery

Novation utilizes its knowledge of mRNA stability regulation to advance its proprietary QUEST drug-discovery technology. QUEST is not limited in its disease or target area application and is especially applicable to so-called non drugable targets, which it is reported make up as much as 90% of currently known disease targets.

QUEST firstly involves the use of proprietary software developed to “mine” the human genome to identify the presence of mRNA stability regulatory elements (SCEs) - either stabilizing or destabilizing. Target genes, in which the mRNA is known to be regulated at the level of mRNA stability, are selected within specific disease areas.

The next step in QUEST is the cloning of the target SCE into a relevant diseased cell and then the production of stable cell lines. The result is a proprietary, highly sensitive, cell based assay system, specific for the targeted gene involved in the disease area of interest. This is optimized for use in High Throughput Screening (HTS) – up to 1536 well plates.

QUEST can be used to screen both proprietary and third party compound libraries to identify small molecules that penetrate the cell, are active and dependent upon the presence of the SCE and so can influence mRNA degradation or stabilization.

Novation’s QUEST system seeks to identify all mRNA stability control elements in the human genome that may work independently or in conjunction with others as a cellular control mechanism. Within QUEST, Novation has patented the approach of developing cell-based assays, based on SCEs contained in mRNAs and used for new drug discovery. The QUEST system enables screening for compounds that elevate or depress mRNA levels of a given gene by specifically affecting mRNA stability, in a high throughput format.

A number of QUEST assays have now been developed covering inflammation, cancer, metabolic and neurodegenerative disease. Other assays are in process. These assays have already been used for high throughput screening of libraries of small molecules and discovered new, specific and potent, compounds that are being developed as new therapeutics for a number of diseases.

The QUEST technology has already been applied in practice and new potential therapeutics for previously intractable targets have been discovered. Novation is employing QUEST to identify products for its own development and also on behalf of pharmaceutical partners.