1378294-19-9Relevant articles and documents
Rapid identification of a novel small molecule phosphodiesterase 10A (PDE10A) tracer
Hu, Essa,Ma, Ji,Biorn, Christopher,Lester-Zeiner, Dianna,Cho, Robert,Rumfelt, Shannon,Kunz, Roxanne K.,Nixey, Thomas,Michelsen, Klaus,Miller, Silke,Shi, Jianxia,Wong, Jamie,Hill Della Puppa, Geraldine,Able, Jessica,Talreja, Santosh,Hwang, Dah-Ren,Hitchcock, Stephen A.,Porter, Amy,Immke, David,Allen, Jennifer R.,Treanor, James,Chen, Hang
, p. 4776 - 4787 (2012/07/28)
A radiolabeled tracer for imaging therapeutic targets in the brain is a valuable tool for lead optimization in CNS drug discovery and for dose selection in clinical development. We report the rapid identification of a novel phosphodiesterase 10A (PDE10A) tracer candidate using a LC-MS/MS technology. This structurally distinct PDE10A tracer, AMG-7980 (5), has been shown to have good uptake in the striatum (1.2% ID/g tissue), high specificity (striatum/thalamus ratio of 10), and saturable binding in vivo. The PDE10A affinity (KD) and PDE10A target density (Bmax) were determined to be 0.94 nM and 2.3 pmol/mg protein, respectively, using [ 3H]5 on rat striatum homogenate. Autoradiography on rat brain sections indicated that the tracer signal was consistent with known PDE10A expression pattern. The specific binding of [3H]5 to rat brain was blocked by another structurally distinct, published PDE10A inhibitor, MP-10. Lastly, our tracer was used to measure in vivo PDE10A target occupancy of a PDE10A inhibitor in rats using LC-MS/MS technology.
