Taget Discovery

Target-based drug discovery for pharma and biopharma

In biopharmaceutical drug discovery labs, the entire workflow is target-based. However, the key challenges lie in pharmaceutical drug discovery, where the target is unknown so target discovery must precede target-based screening. Target discovery is the first stage of drug discovery and development. Identifying a potential target for a new therapeutic drug to combat a previously untreated disease, and validating that target, are undertaken during target discovery. Protein targets are most commonly used, which include enzyme targets, cell-signalling receptors, structural proteins and regulatory factors.

During target-based screening - in contrast to phenotypic screening candidate targets that are already known to be involved in the disease pathway in question are identified and validated.

 

Experiments to demonstrate the target's direct or indirect involvement in the disease are conducted and for the drug to be clinically efficacious, it must bind to the target and modulate its function in a desirable way.
Target validation
measures this biological response, and assesses the drug's ability to induce it appropriately.

Fragment-based screening is a pivotal technology for target discovery. FBS "challenges" a target protein with a library of ligand compounds, in order to determine which (if any) of the ligands exhibit strong binding with that particular protein. Strongly binding ligands become candidates for the basis of further development of molecular targets for the disease in question.

NMR is used to rapidly determine the strength of binding of a ligand with the target, in an automated workflow. By using NMR, R&D laboratories can screen for tens of thousands of compounds to identify which targets to validate and bring forward into lead discovery, and observe binding activity in a time-domain fashion.

By combining NMR and mass spectrometry techniques, structural and molecular weight information can be obtained in tandem for time-efficient target discovery. X-ray crystallography can be used to elucidate the crystal structure of the drug.