NOTUM is a carboxylesterase which depalmitoylates Wnt proteins which results in disruption of Wnt signaling1. NOTUMib-1 inhibits the carboxylesterase activity of NOTUM, IC50=0.085 μM, and restores Wnt signaling. An important new tool for use in cellular disease models in which overactivity of NOTUM suppresses Wnt activity2. NOTUM inhibitors have potential as new therapeutics for degenerative diseaes3.
1) Zhang et al. (2016), Methods for Studying Wnt Protein Modifications/Inactivations by Extracellular Enzymes Tiki and Notum; Methods Mol. Biol., 1481 29
2) Atkinson et al. (2019), Discovery of 2-phenoxyacetamides as inhibitors of the Wnt-depalmitoleating enzyme NOTUM from an X-ray fragment screen; Med. Chem. Commun., Advance Article
3) Suciu et al. (2018), Selective Irreversible Inhibitors of the Wnt-Deacylating Enzyme NOTUM Developed by Activity-Based Protein Profiling; ACS Med. Chem. Lett., 9 563