2篇
您的检索式：作者名="Benjamin Free R"
|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Expression of Native α3β4 Neuronal Nicotinic Receptors: Binding and Functional Studies Investigating Turnover Surface and Intracellular Receptor Populations 显示文摘 | Benjamin Free R Mckay S B Gottlieb P D | 2005 | Mol Pharmacol2005，67，6： | 1 |
| 2 | Identification and optimization of a potent and highly selective D3 dopamine receptor agonist显示文摘OBJECTIVE Dopamine receptors(DRs) are involved in the development and treatment of many neuropsychiatric disorders.Currently available dopaminergic drugs modulate both DRD2 and DRD3,leading to side effects and uncertainty as to the roles each DR subtype plays physiologically.Our lab employed high throughput screening paradigms to discover highly selective modulators for the DRD3.METHODS The NIH Molecular Libraries Program 400,000 + small molecule library was screened using the Discove Rx Path Hunter?β-arrestin assay for compounds that activate the DRD3 without effects on the DRD2.Confirmation and counter-screens assessed selectivity and mechanisms of action.We identified 62 potential agonists,and chose the most promising to perform a structure-activity relationship(SAR) study to increase potency while maintaining selectivity.The lead compound identified through this process,ML417,was also characterized using bioluminescence resonance energy transfer(BRET)-based β-arrestin recruitment and G-protein activation assays as well as p-ERK assays.Potential neuroprotective properties of this compound were assessed using a SHSY5 Y neuronal cell model.RESULTS ML417 displays potent,DRD3-selective agonist activity in multiple functional assays.Binding and functional GPCR screens(>165 receptors) show ML417 has limited cross-reactivity with other GPCRs.ML417 also displays superior(compared to the reference compound pramipexole),dose-dependent protection against a decrease in neurite length induced by 10 μmol·L^(-1) of the neurotoxin,6-hydroxydopamine,in the SHSY5 Y cell model.CONCLUSION We have discovered and characterized ML417,a potent and highly selective DRD3 agonist.This compound will be useful as a research tool,and may prove useful as a therapeutic drug lead. | Amy E MORITZ R Benjamin FREE Warren WEINER Muzna BACHANI Trevor DOYLE Noel SOUTHALL Marc FERRER Jonathan A JAVITCH Joseph STEINER Ara ABRAMYAN Lei SHI Jeffrey AUBé Kevin FRANKOWSKI David R SIBLEY | 2017 | 中国药理学与毒理学杂志2017，31，10： | 0 |
您所在的机构暂未开通此部分的功能，请联系管理员