NOTUM (Wnt signaling) Library

ChemDiv’s NOTUM (Wnt Signaling) Library provides 4,000 compounds.

NOTUM is an enzyme that plays a significant role in drug discovery, particularly in the context of Wnt signaling pathway modulation. It acts as a carboxylesterase and is known for its role in the Wnt signaling pathway, which is crucial in cell development, proliferation, and differentiation. NOTUM specifically deacylates Wnt proteins, which can attenuate Wnt signaling. Due to its role in the Wnt pathway, NOTUM has been implicated in various diseases, including cancer, degenerative diseases, and developmental disorders. Inhibiting or modulating NOTUM can potentially influence these disease processes. This has potential therapeutic implications in diseases where Wnt signaling is aberrant.

The dysregulation of Wnt signaling is commonly associated with growth-related pathologies and various cancers, especially in tissues where Wnt normally promotes self-renewal and repair. Furthermore, Wnt signaling has been implicated in neurodegenerative diseases, including Alzheimer’s disease. The O-palmitoleoylation of a conserved serine residue in Wnt proteins is a crucial post-translational modification for effective binding to Frizzled receptors, which is necessary for signal transduction. Previously, the carboxylesterase NOTUM was shown to antagonize Wnt signaling pathways. More recent findings demonstrate that NOTUM suppresses Wnt signaling by mediating the depalmitoleoylation of Wnt proteins [1].

Developing inhibitors or modulators of NOTUM is challenging due to the complexity of the Wnt pathway and the need for specificity. Our recent advances in understanding the structure and function of NOTUM have facilitated the development of targeted ligands, and the results of our research studies are summarized in our focused library.

References:
[1] B. N. Atkinson et al., “Discovery of 2-phenoxyacetamides as inhibitors of the Wnt-depalmitoleating enzyme NOTUM from an X-ray fragment screen,” Medchemcomm, vol. 10, no. 8, pp. 1361–1369, 2019, doi: 10.1039/c9md00096h.