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Updated: Jun 25, 2026

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
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Discovery of the First-in-class G9a/GLP PROTAC Degrader

Julia Velez1, Yulin Han1, Hyerin Yim1

  • 1Mount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Science, Oncological Science and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Biorxiv : the Preprint Server for Biology
|March 11, 2024
PubMed

Insights

We developed a novel PROTAC degrader, compound 10 (MS8709), that effectively degrades G9a/GLP proteins. This new therapeutic shows promise for treating cancers dependent on G9a/GLP activity.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Aberrant expression of lysine methyltransferases G9a and GLP is linked to cancer development.
  • G9a/GLP exhibit both catalytic and non-catalytic oncogenic functions.
  • Existing G9a/GLP catalytic inhibitors show limited anticancer efficacy.

Conclusions:

  • Compound 10 represents the first G9a/GLP PROTAC degrader with significant therapeutic potential.
  • Compound 10 serves as a valuable chemical biology tool for studying G9a/GLP functions.
  • Compound 10 holds promise for treating cancers driven by G9a/GLP activity.

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