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Discovery of TDI-10229: A Potent and Orally Bioavailable Inhibitor of Soluble Adenylyl Cyclase (sAC, ADCY10).
Fushimi, Makoto Buck, Hannes Balbach, Melanie Gorovyy, Anna Ferreira, Jacob Rossetti, Thomas Kaur, Navpreet Levin, Lonny R Buck, Jochen Quast, Jonathan
Fushimi, Makoto
Buck, Hannes
Balbach, Melanie
Gorovyy, Anna
Ferreira, Jacob
Rossetti, Thomas
Kaur, Navpreet
Levin, Lonny R
Buck, Jochen
Quast, Jonathan
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2021-07-14
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Abstract
Soluble 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.
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ACS Med Chem Lett. 2021 Jul 14;12(8):1283-1287. doi: 10.1021/acsmedchemlett.1c00273.
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en
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1948-5875
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Attribution 4.0 International