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Related Experiment Videos

Rationalizing Promiscuity Cliffs.

Dilyana Dimova1, Jürgen Bajorath1

  • 1Department of Life Science Informatics, Bonn-Aachen International Center for Information Technology, Rheinische Friedrich-Wilhelms-Universität Bonn, Dahlmannstr. 2, 53113, Bonn, Germany.

Chemmedchem
|October 13, 2017
PubMed
Summary
This summary is machine-generated.

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This study differentiates "good" compound promiscuity (true multitarget activity) from "bad" promiscuity. Promiscuity cliffs (PCs) reveal structure-activity relationships for multitarget small molecules.

Area of Science:

  • Medicinal Chemistry
  • Chemical Biology
  • Drug Discovery

Background:

  • Compound promiscuity, the ability of a molecule to interact with multiple biological targets, is a complex phenomenon.
  • Distinguishing beneficial multitarget activities from detrimental off-target effects is crucial for drug development.
  • Understanding the molecular underpinnings of compound promiscuity is essential for rational drug design.

Purpose of the Study:

  • To explore structure-promiscuity relationships (SPRs) to understand the molecular basis of multitarget activities.
  • To introduce and define "promiscuity cliffs" (PCs) as a novel concept for analyzing SPRs.
  • To investigate the utility of PCs in identifying and rationalizing true multitarget activities of small molecules.

Main Methods:

  • Definition and application of the "promiscuity cliff" (PC) concept, an extension of activity cliffs (ACs).
Keywords:
active compoundsactivity cliffsmultitarget activitypromiscuity cliffsstructure-promiscuity relationships

Related Experiment Videos

  • Analysis of structural analogues exhibiting differential activity across multiple targets.
  • Identification of surprising SPRs through the PC framework.

    • Main Results:

    • PCs effectively capture complex and often unexpected structure-promiscuity relationships.
    • The PC concept provides a framework for understanding how subtle structural changes impact multitarget engagement.
    • PCs generate numerous experimentally verifiable hypotheses regarding molecular interactions.

    Conclusions:

    • Promiscuity cliffs are a valuable tool for dissecting the molecular basis of "good" compound promiscuity.
    • PCs facilitate the discovery and optimization of small molecules with desired multitarget profiles.
    • This approach aids in advancing the scientific understanding and therapeutic relevance of multitarget drug discovery.