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Updated: Apr 18, 2026

Using High Content Imaging to Quantify Target Engagement in Adherent Cells
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Target engagement in lead generation.

Timothy B Durham1, Maria-Jesus Blanco1

  • 1Discovery Chemistry Research and Technologies, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.

Bioorganic & Medicinal Chemistry Letters
|January 30, 2015
PubMed
Summary
This summary is machine-generated.

Drug discovery faces challenges with low approvals despite high R&D investment. Integrating target engagement assessment early in lead generation improves drug development success rates.

Keywords:
Bioluminescent imaging (BLI)BiomarkerCellular thermal shift assay (CETSA)Lead GenerationPositron emission tomography (PET)Receptor occupancy (RO)Target engagement

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Area of Science:

  • Pharmaceutical Sciences
  • Drug Discovery and Development
  • Medicinal Chemistry

Background:

  • The pharmaceutical industry experiences low new drug approval rates despite substantial research and development (R&D) investment.
  • Current drug discovery approaches often struggle with effective target selection and clinical hypothesis validation.
  • There is a critical need to enhance early-stage drug discovery processes to improve success rates.

Purpose of the Study:

  • To highlight the importance of an integrated drug discovery approach starting from the Lead Generation phase.
  • To emphasize the evaluation of target engagement within the target tissue.
  • To demonstrate the value of linking preclinical data to clinical readouts for medicinal chemistry efforts.

Main Methods:

  • Review of current strategies and technologies for assessing target engagement.
  • Analysis of the application of target engagement assessment in medicinal chemistry.
  • Discussion of methods for linking preclinical and clinical data.

Main Results:

  • Early assessment of target engagement in the target tissue is crucial for successful drug development.
  • Integrated approaches improve target selection and clinical hypothesis validation.
  • Specific strategies and technologies can effectively evaluate target engagement.

Conclusions:

  • Implementing target engagement assessments early in drug discovery is vital for improving the efficiency of R&D investment.
  • Medicinal chemistry efforts benefit significantly from understanding target engagement and its correlation with clinical outcomes.
  • An integrated drug discovery strategy focusing on target engagement enhances the probability of successful drug approvals.