CETSA and its Role in Target Engagement

Faced with ever-increasing costs in developing and bringing pharmaceuticals to market, pharma companies are placing greater emphasis in pre-clinical validation of their drug candidates. An area receiving such attention is validation of Target Engagement, i.e., confirming that a ligand exerts its pharmaceutical effects by binding its intended target biomolecule and not through off-target interactions.

While methodologies for measuring Target Engagement have existed for some time, most approaches are either:

• Based on affinity assays that are only applicable to purified proteins
• Dependent on cloning, restricting their use to a limited range of cell lines
• Simply not applicable in sufficiently high throughput

The CEllular Thermal Shift Assay (CETSA^®), a patented technology from Pelago Biosciences, exploits the thermal stability conferred to a protein following the binding of a compound. Combined with 爱游戏平台注册登录 ’s no-wash dual antibody proximity assays such as AlphaLISA or HTRF, CETSA^® offers the unique advantages of a cellular assay that can be used on primary cells or even tissues, in a high-throughput fashion.

This white paper:

• Introduces Target Engagement and its importance in drug discovery
• Discusses different methodologies for measuring Target Engagement, their advantages, and shortcomings
• Reviews CETSA^®, its mode of action and applications
• Presents two real-life case studies of industrial adoption of CETSA^®, by Vertex Pharmaceuticals and AstraZeneca