Beilstein J. Org. Chem.2019,15, 2790–2797, doi:10.3762/bjoc.15.271
, Kings Cross, London NW1 1AT, UK 10.3762/bjoc.15.271 Abstract Background: The carboxylesterase Notum has been shown to act as a key negative regulator of the Wnt signalling pathway by mediating the depalmitoleoylation of Wnt proteins. LP-922056 (1) is an orally active inhibitor of Notum. We are
1 (or 17) which combines Notum inhibition with CNS penetration would be a valuable chemical probe for investigating the role of Notum in disease models.
Keywords: brain penetration; 1-chloro-1,2-benziodoxol-3-one; electrophilic chlorination; LP-922056; Notum inhibitor; Introduction
The Wnt
Wnt proteins is required for efficient binding to Frizzled receptors and the subsequent signal transduction. The carboxylesterase Notum has been shown to act as a key negative regulator of the Wnt signalling pathway by specifically mediating the depalmitoleoylation of Wnt proteins [3][4].
LP-922056 (1
PDF
Graphical Abstract
Figure 1:
Chemical structure of Notum inhibitor LP-922056 (1).