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PDBsum entry 4zo5
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Hydrolase/hydrolase inhibitor
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PDB id
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4zo5
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References listed in PDB file
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Key reference
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Title
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Discovery of [¹¹c]mk-8193 as a pet tracer to measure target engagement of phosphodiesterase 10a (pde10a) inhibitors.
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Authors
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C.D.Cox,
E.D.Hostetler,
B.A.Flores,
J.L.Evelhoch,
H.Fan,
L.Gantert,
M.Holahan,
W.Eng,
A.Joshi,
G.Mcgaughey,
X.Meng,
M.Purcell,
I.T.Raheem,
K.Riffel,
Y.Yan,
J.J.Renger,
S.M.Smith,
P.J.Coleman.
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Ref.
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Bioorg Med Chem Lett, 2015,
25,
4893-4898.
[DOI no: ]
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PubMed id
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Abstract
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Phosphodiesterase 10A (PDE10A) inhibition has recently been identified as a
potential mechanism to treat multiple symptoms that manifest in schizophrenia.
In order to facilitate preclinical development and support key proof-of-concept
clinical trials of novel PDE10A inhibitors, it is critical to discover positron
emission tomography (PET) tracers that enable plasma concentration/PDE10A
occupancy relationships to be established across species with structurally
diverse PDE10A inhibitors. In this Letter, we describe how a high-throughput
screening hit was optimized to provide [(11)C]MK-8193 (8j), a PET tracer that
supports the determination of plasma concentration/PDE10A occupancy
relationships for structurally diverse series of PDE10A inhibitors in both rat
and rhesus monkey.
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