3篇
您的检索式：作者名="Arthur Christopoulos"
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| 1 | 向在人的察觉到钙的受体的 allosteric 药的结构的理解显示文摘allosterically 指向人的察觉到钙的受体(CaSR ) 的药有实质的治疗学的潜力,但是当前被限制。给 CaSR 的高分辨率的结构的缺席,我们把 mutagenesis 与一条新奇分析途径并且开发 “ 的分子的建模相结合; enriched”为在 Ca 2+ 在 CaSRs 7 transmembrane (7TM ) 以内的 o 和 allosteric 调节的人领域。修改多重有约束力的地点以适应在结构上的一个扩大的洞多样的 ligands 被识别。Phenylalkylamines 绑在与通常认为的 Ca 2+ o -binding 地点并且向一个细胞外的门厅延长。相反,在结构上和 pharmacologically 不同的 AC-265347 在 7TM 领域以内更深绑。而且,不同氨基酸网络被发现调停由不同调节的人的 cooperativity。这些调查结果可以与不同、潜在地偏导小径的药理学效果便于 allosteric 调节的人的合理设计。 | Katie Leach Karen J Gregory Irina Kufareva Elham Khajehali Anna E Cook Ruben Abagyan Arthur D Conigrave Patrick M Sexton Arthur Christopoulos | 2016 | Cell Research2016，26，5： | 2 |
| 2 | Impact of chronic congestive heart failure on pharmacokinetics and vasomotor effects of infused nitrite显示文摘 | Abdul R Maher Sayqa Arif Melanie Madhani Khalid Abozguia Ibrar Ahmed Bernadette O Fernandez Martin Feelisch AG O’Sullivan Arthur Christopoulos Aaron L Sverdlov Doan Ngo Rustem Dautov Philip E James John D Horowitz Michael P Frenneaux | 2013 | Br J Pharmacol2013，，3： | 1 |
| 3 | Structure-activity relationship of pyrazol-4-ylpyridine derivatives and identification of a radiofluorinated probe for imaging the muscarinic acetylcholine receptor M4显示文摘There is an accumulating body of evidence implicating the muscarinic acetylcholine receptor4(M4)in schizophrenia and dementia with Lewy bodies,however,a clinically validated M4positron emission tomography(PET)radioligand is currently lacking.As such,the aim of this study was to develop a suitable M4PET ligand that allows the non-invasive visualization of M4in the brain.Structure-activity relationship studies of pyrazol-4-yl-pyridine derivates led to the discovery of target compound 12—a subtype-selective positive allosteric modulator(PAM).The radiofluorinated analogue,[18F]12,was synthesized in 28±10%radiochemical yield,>37 GBq/μmol and an excellent radiochemical purity>99%.Initial in vitro autoradiograms on rodent brain sections were performed in the absence of carbachol and showed moderate specificity as well as a low selectivity of[18F]12 for the M4-rich striatum.However,in the presence of carbachol,a significant increase in tracer binding was observed in the rat striatum,which was reduced by>60%under blocking conditions,thus indicating that orthosteric ligand interaction is required for efficient binding o f[18F]12 to the allosteric site.Remarkably,however,the presence of carbachol was not required for high specific binding in the non-human primate(NHP)and human striatum,and did not further improve the specificity and selectivity of[18F]12 in higher species.These results pointed towards significant species-differences and paved the way for a preliminary PET study in NHP,where peak brain uptake of[18F]12 was found in the putamen and temporal cortex.In conclusion,we report on the identification and preclinical development of the first radiofluorinated M4PET radioligand with promising attributes.The availability of a clinically validated M4PET radioligand harbors potential to facilitate drug development and provide a useful diagnostic tool for non-invasive imaging. | Ahmed Haider Xiaoyun Deng Olivia Mastromihalis Stefanie K.Pfister Troels E.Jeppesen Zhiwei Xiao Vi Pham Shaofa Sun Jian Rong Chunyu Zhao Jiahui Chen Yinlong Li Theresa R.Connors April T.Davenport James B.Daunais Vahid Hosseini Wenqing Ran Arthur Christopoulos Lu Wang Celine Valant Steven H.Liang | 2023 | Acta Pharmaceutica Sinica B2023，13，1： | 0 |
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