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Related Experiment Videos

Rethinking target discovery in polygenic diseases.

Christodoulos S Flordellis1, Antonis S Manolis, Hervé Paris

  • 1Department of Pharmacology, School of Medicine, University of Patras, Greece. flordell@med.upatras.gr

Current Topics in Medicinal Chemistry
|October 5, 2006
PubMed
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Drug development reform is needed due to low success rates. Rethinking molecular and clinical targets, especially for polygenic diseases, can improve pharmacological interventions by targeting component dysfunctions.

Area of Science:

  • Pharmacology
  • Drug Discovery
  • Translational Medicine

Background:

  • Despite significant R&D investment, new drug yields are low, indicating a need for reform in drug development.
  • Current target identification faces a translational bottleneck due to limitations in target validation platforms.
  • Clinical disease entities are complex, with intricate pathophysiologic mechanisms and manifestations.

Purpose of the Study:

  • To discuss limitations in current molecular target discovery, focusing on selectivity and efficacy.
  • To describe constraints on drug development imposed by diagnostic constructs and phenotype dissection.
  • To propose new pharmacological intervention strategies for polygenic diseases by targeting component dysfunctions.

Main Methods:

  • Analysis of limitations in molecular target discovery and validation platforms.

Related Experiment Videos

  • Examination of diagnostic constructs and their impact on drug development.
  • Exploration of strategies for targeting component dysfunctions in polygenic diseases.

    • Main Results:

    • Current molecular target discovery approaches exhibit limitations in selectivity and efficacy.
    • Diagnostic constructs and the dissection of clinical phenotypes pose constraints on drug development.
    • Reconsidering targets in polygenic diseases can lead to novel intervention strategies.

    Conclusions:

    • Drug development requires rethinking, particularly in target discovery and validation.
    • New strategies for polygenic diseases involve targeting component dysfunctions rather than the whole phenotype.
    • Combination therapies or multi-targeted drugs offer promising avenues for improved pharmacological intervention.