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Updated: Nov 8, 2025

Functional Characterization of Carboxylesterases in Insecticide Resistant House Flies, Musca Domestica
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Small-molecule inhibitors of carboxylesterase Notum

Yuguang Zhao1, Sarah Jolly2, Stefano Benvegnu2

  • 1Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford, OX3 7BN, UK.

Future Medicinal Chemistry
|April 22, 2021
PubMed

Insights

Notum negatively regulates Wnt signaling by removing a palmitoleate group from Wnt proteins. Inhibiting Notum offers a potential therapeutic strategy for cancer, osteoporosis, and neurodegenerative diseases.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Drug Discovery

Background:

  • Notum is identified as a negative regulator of Wnt signaling.
  • It functions by removing a palmitoleate group from Wnt proteins.
  • Emerging evidence links Notum to human diseases like cancer, osteoporosis, and neurodegenerative disorders.

Purpose of the Study:

  • To explore the role of Notum in human diseases.
  • To identify and develop small-molecule inhibitors of Notum.
  • To advance the understanding of Notum's function and therapeutic potential.

Main Methods:

  • High-throughput screening
  • Activity-based protein profiling
  • Fragment library screening
  • Virtual screening campaigns
  • Structural studies

Main Results:

  • Several hit-finding strategies were successfully applied.
  • Structural studies are facilitating the discovery of Notum inhibitors.
  • Specific inhibitors like LP-922056, ABC99, and ARUK3001185 have been identified.

Conclusions:

  • Targeting Notum presents a novel therapeutic avenue for various human diseases.
  • Small-molecule inhibitors of Notum are crucial tools for further research.
  • Continued investigation will deepen the understanding of Notum's role in disease pathogenesis.
Keywords:
Notum inhibitorsWnt signalingactivity-based protein profilingfragment screeninghigh-throughput screeninghit-finding strategiesstructural biologyvirtual screening

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