7OVD

Human soluble adenylyl cyclase in complex with the inhibitor TDI10229

Summary for 7OVD

• Entry DOI: 10.2210/pdb7ovd/pdb
• Descriptor: Adenylate cyclase type 10, 4-chloranyl-6-[1,5-dimethyl-4-(phenylmethyl)pyrazol-3-yl]pyrimidin-2-amine, ACETATE ION, ... (6 entities in total)
• Functional Keywords: soluble adenylyl cyclase, adcy10, signaling enzyme, class iii cyclase, signaling protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 55504.57

Authors

Steegborn, C.,Quast, J. (deposition date: 2021-06-14, release date: 2021-10-06, Last modification date: 2024-10-16)

Primary citation

Fushimi, M.,Buck, H.,Balbach, M.,Gorovyy, A.,Ferreira, J.,Rossetti, T.,Kaur, N.,Levin, L.R.,Buck, J.,Quast, J.,van den Heuvel, J.,Steegborn, C.,Finkin-Groner, E.,Kargman, S.,Michino, M.,Foley, M.A.,Miller, M.,Liverton, N.J.,Huggins, D.J.,Meinke, P.T.
Discovery of TDI-10229: A Potent and Orally Bioavailable Inhibitor of Soluble Adenylyl Cyclase (sAC, ADCY10).
Acs Med.Chem.Lett., 12:1283-1287, 2021

PubMed 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 interrogation of sAC inhibition to assess its potential therapeutic applications. This work culminated in the identification of TDI-10229 (), which displays nanomolar inhibition of sAC in both biochemical and cellular assays and exhibits mouse pharmacokinetic properties sufficient to warrant its use as an tool compound.

PubMed: 34413957
DOI: 10.1021/acsmedchemlett.1c00273

Experimental method

X-RAY DIFFRACTION (2.2 Å)