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Related Experiment Video

Updated: Feb 13, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
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Identification and Structure-Guided Development of Pyrimidinone Based USP7 Inhibitors.

Colin R O'Dowd1, Matthew D Helm1, J S Shane Rountree1

  • 1Almac Discovery Ltd., Centre for Precision Therapeutics, 97 Lisburn Road, Belfast, Northern Ireland BT9 7AE, United Kingdom.

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Researchers developed potent USP7 inhibitors for drug discovery, targeting cancer and other diseases. These novel compounds show promise for further research into ubiquitin specific protease 7

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Area of Science:

  • Biochemistry and Drug Discovery
  • Oncology
  • Molecular Biology

Background:

  • Ubiquitin specific protease 7 (USP7, HAUSP) is crucial in regulating Mdm2 and p53 protein levels.
  • USP7 is implicated in cancer, metabolic disorders, immune diseases, and viral infections, making it a key drug target.
  • High-resolution cocrystallography has facilitated structure-guided drug design.

Purpose of the Study:

  • To develop potent, novel, and selective inhibitors of USP7.
  • To explore the structure-activity relationships of these inhibitors.
  • To advance compounds for potential in vivo studies.

Main Methods:

  • Fragment-based screening, scaffold-hopping, and hybridization techniques were employed for initial hit identification.
  • Rational and structure-guided design approaches were utilized.
  • High-resolution cocrystallography data informed the design process.

Main Results:

  • Development of two distinct subseries of USP7 inhibitors.
  • Identification of structure-activity relationship trends for the novel compounds.
  • Initial progress in creating compounds suitable for in vivo evaluation.

Conclusions:

  • Novel and selective USP7 inhibitors have been successfully developed.
  • These inhibitors provide valuable tools for further investigation of USP7's biological roles.
  • The findings support continued research into USP7 as a therapeutic target for various diseases.