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Application of MassSQUIRM for Quantitative Measurements of Lysine Demethylase Activity
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LSD1 Histone Demethylase Assays and Inhibition.

D Hayward1, P A Cole1

  • 1Johns Hopkins School of Medicine, Baltimore, MD, United States.

Methods in Enzymology
|July 4, 2016
PubMed
Summary
This summary is machine-generated.

Lysine-specific demethylase 1 (LSD1) is an enzyme targeting gene silencing. This chapter reviews methods to assay LSD1 activity and inhibitors for therapeutic applications in cancer.

Keywords:
Amine oxidaseCyclopropylamineHistoneHydrazineInhibitorKineticsMass spectrometry

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Area of Science:

  • Biochemistry
  • Epigenetics
  • Enzymology

Background:

  • Lysine-specific demethylase 1 (LSD1) is a flavin-dependent enzyme crucial for epigenetic gene regulation.
  • LSD1 removes methyl groups from histone H3 at Lys4, influencing gene expression.
  • LSD1 is implicated as a therapeutic target in various diseases, including cancer.

Purpose of the Study:

  • To discuss methods for measuring LSD1 demethylase activity.
  • To review chemical inhibitors targeting LSD1, focusing on those derived from monoamine oxidase inhibitors.
  • To highlight recent LSD1 mechanism-based inactivators and their biomedical relevance.

Main Methods:

  • Assays for measuring LSD1 demethylase activity.
  • Review of chemical scaffolds from monoamine oxidase inhibitors for LSD1 inhibition.
  • Analysis of recently developed LSD1 mechanism-based inactivators.

Main Results:

  • Various methods exist to measure LSD1 activity, each with strengths and limitations for drug discovery.
  • Established chemical groups from monoamine oxidase inhibitors show potential for LSD1 inhibition.
  • Novel mechanism-based inactivators offer new avenues for LSD1-targeted therapies.

Conclusions:

  • Accurate measurement of LSD1 activity is vital for inhibitor development.
  • LSD1 inhibitors, particularly those inspired by MAOIs, represent a promising therapeutic strategy.
  • Mechanism-based inactivators are advancing the potential of LSD1-targeted biomedical applications.