Rediscovering Drug Research

Preventing non-effective drugs from entering costly (pre-)clinical trials is crucial for successful drug discovery. Scientists can benefit and accelerate this process by gaining a better understanding of the underlying biological mechanisms of targets and the mechanism of action of promising leads. We offer solutions that enable researchers to directly observe complex dynamic molecular processes and identify the most promising leads.

Dynamic Single-Molecule analysis

One of the big challenges in Drug Discovery today is that all current life science tools working at the molecular level either measure static structure or average binding kinetics; the crucial and often very complex mechanical details of the underlying dynamic process are often not revealed. Dynamic Single-Molecule (DSM) analysis reveals these details. This reduces the risk of failure of drugs in costly late-stage clinical trials, thereby decreasing the overall cost of drug development dramatically.

DSM analysis has the unique ability to combine live imaging, manipulation and force-displacement measurement with Ångström precision for the study of DNA-protein interactions and protein conformational changes. This combination gives the crucial dynamic and functional mechanistic information that is complementary to structural data (X-ray crystallography) and ensemble average kinetics (SPR or calorimetry). In pharma, DSM can play a significant role in two stages of the Drug Discovery Process: Target Validation, and Hit-to-Lead.

Target Validation

Successful drug design starts with obtaining a detailed mechanistic understanding of the target.

Hit Identification

Hit-to-lead

The inability to understand the mechanism of action can result in non-effective drugs entering costly (pre-)clinical trials.

Lead Optimization

Applications of DSM in drug discovery

Study protein conformational changes in real-time at the single-molecule level

  • Study the mechanism behind the biological function of proteins by looking at the conformational changes of protein targets, in real-time and with Ångström resolution
  • Observe conformational changes of protein targets in the presence of different pharmaceuticals. Find out whether the desired mechanism(s) of action is fulfilled by the drug in a quick, easy and effective manner

Visualize and measure DNA-protein interactions in real-time at the single-molecule level

  • Achieve better target validation and understanding of the druggable mechanism of action early in the process by investigating the complex dynamic molecular mechanisms of DNA-protein interactions
  • Visualize and measure the dynamics of DNA-protein interactions under the influence of pharmaceuticals to gain insight into the drug’s mechanism of action

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