Merck, SML2410-25MG, ABC99

Biochem/physiol Actions
ABC99 is an N-hydroxyhydantoin (NHH) carbamate-based irreversible, potent and selective inhibitor against the serine hydrolase activity of the Wnt-deacylating enzyme NOTUM (IC50 = 13 nM against NOTUM-mediated labeling of fluorophosphonate (FP) probe), an enzyme that reverses the posttranslational O-linked palmitoleate modification of Wnt proteins. ABC99 prevents NOTUM-mediated negative regulation against Wnt3A-dependent cellular signaling (EC50 = 89 nM by HEK293T TOPflash reporter assay) with excellent selectivity over 65 other serine hydrolases, including PPT1.
Irreversible, potent and selective inhibitor against NOTUM serine hydrolase activity and sustanins Wnt3A-dependent signaling in the presence of NOTUM.
Inhibition of NOTUM has therapeutic use in treating degenerative diseases including osteopenia and osteoporosis.