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DZNep: A Methyltransferase Modulator for Disease Mitigation.

Sarita Garg1, Isabelle R Miousse1

  • 1Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.

Environmental and Molecular Mutagenesis
|June 25, 2026
PubMed
Summary

3-deazaneplanocin A (DZNep) inhibits S-adenosylhomocysteine hydrolase, impacting over 150 enzymes. Preclinical studies show its potential as an anticancer, antifibrotic, and anti-inflammatory agent with a favorable safety profile.

Keywords:
EZH2cancerfibrosisinflammationmethylationmethyltransferases

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Area of Science:

  • Biochemistry
  • Pharmacology
  • Molecular Biology

Background:

  • 3-deazaneplanocin A (DZNep) is recognized as an inhibitor of histone methyltransferase EZH2.
  • DZNep's primary mechanism involves inhibiting S-adenosylhomocysteine hydrolase (SAHH).
  • SAHH inhibition leads to broad pan-methyltransferase inhibition affecting numerous enzyme targets.

Purpose of the Study:

  • To review preclinical evidence of DZNep's therapeutic potential in various disease models.
  • To evaluate DZNep's efficacy as an anticancer, antifibrotic, and anti-inflammatory agent.
  • To assess the safety profile and potential mechanisms of DZNep beyond EZH2 inhibition.

Main Methods:

  • Synthesis of evidence from preclinical studies.
  • Analysis of DZNep's effects in diverse animal models of disease.
  • Evaluation of reported safety and toxicology data.

Main Results:

  • DZNep demonstrates significant benefits in limiting disease development in animal models.
  • The compound shows particular promise as an anticancer and antifibrotic agent.
  • Consistent anti-inflammatory effects and a favorable safety profile at therapeutic doses were observed.

Conclusions:

  • DZNep's broad therapeutic activity suggests mechanisms beyond EZH2 inhibition.
  • Clinical translation is essential to validate DZNep's potential and safety.
  • DZNep represents a promising multi-target therapeutic agent for diverse pathological processes.