Integrated Calendar

Recently developed DIANA platform (DNA-linked Inhibitor ANtibody Assay) is suitable for both ultrasensitive protein detection in in vitro diagnostics and for enzyme inhibitor or protein ligand screening in drug discovery. As its name suggests, we originally designed DIANA to detect enzymes and its inhibitors, but we later showed that it is well suited also for detection of receptors and its ligands, to screen for protein-protein interaction inhibitors and for detection of small molecules. DIANA overcomes the limitations of current state of the art methods, as it can detect zeptomole amounts of targets, has a linear range of up to six logs and is applicable to biological matrices.

Screening of chemical libraries is an important step in drug discovery, but it remains challenging for targets, which are difficult to express and purify, and current methods tend to produce false results. The sensitivity and selectivity of DIANA enables quantitative high-throughput screening of enzyme inhibitors, receptor ligands or inhibitors of protein-protein interactions with unpurified proteins. DIANA addresses also the remaining limitations of the current screening methods, as it allows high-throughput screening with high signal-to-noise ratio (Z’ factor > 0.9), sensitive hit discovery and ultralow rate of false positives (< 0.02%); while quantitatively determining the inhibition potency from a single well and requiring only picogram to nanogram quantities of potentially unpurified protein target (e.g. in human serum).

At DIANA Biotechnologies, a recently established spin-off from the Institute of Organic Chemistry and Biochemistry in Prague, we aim to fully exploit the potential of the platform and to become center for development of new diagnostics and drug discovery. We are building up infrastructure for screening and hit to lead conversion, including our own ~150,000 compound library, which we will screen for medicinally relevant targets, taking just one week per target. The most promising compounds will be optimized for potency, selectivity, physical properties, pharmacology profile and in vitro and in vivo efficacy, where DIANA-based high-throughput ADME pharmacology tests can also be applied.

In our talk, we will briefly summarize the assay protocol and its performance on model targets, as well as recent developments at DIANA Biotechnologies. We will discuss in more detail examples of current internal projects, mainly of the development of selectivity panels (example of inhibitors of human carbonic anhydrases) and of the first drug discovery project directed on influenza RNA polymerase and its different subunits.