- COMPOUND OF CAMPTOTHECIN AND PREPARATION AND USE THEREOF
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The present disclosure relates to a compound of formula I, a pharmaceutical composition thereof and the use thereof as an anti-tumor drug.
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- COMPOUND OF CAMPTOTHECIN AND PREPARATION AND USE THEREOF
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The present disclosure relates to a compound of formula I, a pharmaceutical composition thereof and the use thereof as an anti-tumor drug.
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- Rapid identification of a novel small molecule phosphodiesterase 10A (PDE10A) tracer
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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.
- 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
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experimental part
p. 4776 - 4787
(2012/07/28)
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- PHOSPHODIESTERASE 10 INHIBITORS
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The present invention if directed to certain cinnoline compounds that are PDE10 inhibitors, pharmaceutical compositions containing such compounds and processes for preparing such compounds. The invention is also directed to methods of treating diseases mediated by PDE10 enzyme, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.
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Page/Page column 65
(2008/06/13)
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