Discovery of TDI-10229: A Potent and Orally Bioavailable Inhibitor of Soluble Adenylyl Cyclase (sAC, ADCY10).
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Levin, Lonny R
van den Heuvel, Joop
Foley, Michael A
Liverton, Nigel J
Huggins, David J
Meinke, Peter T
MetadataShow full item record
AbstractSoluble adenylyl cyclase (sAC) has gained attention as a potential therapeutic target given the role of this enzyme in intracellular signaling. We describe successful efforts to design improved sAC inhibitors amenable for in vivo interrogation of sAC inhibition to assess its potential therapeutic applications. This work culminated in the identification of TDI-10229 (12), which displays nanomolar inhibition of sAC in both biochemical and cellular assays and exhibits mouse pharmacokinetic properties sufficient to warrant its use as an in vivo tool compound.
CitationACS Med Chem Lett. 2021 Jul 14;12(8):1283-1287. doi: 10.1021/acsmedchemlett.1c00273.
AffiliationHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
JournalACS medicinal chemistry letters
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