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排序方式: 共有198条查询结果,搜索用时 15 毫秒
31.
Steven J. Taylor Fariba Soleymanzadeh Anne B. Eldrup Neil A. Farrow Ingo Muegge Alison Kukulka Alisa K. Kabcenell Stephane De Lombaert 《Bioorganic & medicinal chemistry letters》2009,19(20):5864-5868
A series of potent nicotinamide inhibitors of soluble epoxides hydrolase (sEH) is disclosed. This series was designed using structure-based deconstruction and a combination of two HTS hit series, resulting in hybrid analogs that retained the optimal potency from one series, and acceptable in vitro metabolic stability from the other. Structure-guided optimization of these analogs gave rise to nanomolar inhibitors of human sEH that had acceptable plasma exposure to qualify them as probes to determine the in vivo phenotypic consequences of sEH inhibition. 相似文献
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Alexander Heim-Riether Steven J. Taylor Shuang Liang Donghong Amy Gao Zhaoming Xiong E. Michael August Brandon K. Collins Bennett T. Farmer II Kathleen Haverty Melissa Hill-Drzewi Hans-Dieter Junker S. Mariana Margarit Neil Moss Thomas Neumann John R. Proudfoot Lana Smith Keenan Renate Sekul Qiang Zhang Jun Li Neil A. Farrow 《Bioorganic & medicinal chemistry letters》2009,19(18):5321-5324
Discovery and optimization of potency and selectivity of a non-Zn-chelating MMP-13 inhibitor with the aid of protein co-crystal structural information is reported. This inhibitor was observed to have a binding mode distinct from previously published MMP-13 inhibitors. Potency and selectivity were improved by extending the hit structure out from the active site into the S1′ pocket. 相似文献
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Diego A. Miranda Ji-Hyun Kim Long N. Nguyen Wang Cheng Bryan C. Tan Vera J. Goh Jolene S. Y. Tan Jadegoud Yaligar Bhanu Prakash KN S. Sendhil Velan Hongyan Wang David L. Silver 《The Journal of biological chemistry》2014,289(14):9560-9572
Triglycerides within the cytosol of cells are stored in a phylogenetically conserved organelle called the lipid droplet (LD). LDs can be formed at the endoplasmic reticulum, but mechanisms that regulate the formation of LDs are incompletely understood. Adipose tissue has a high capacity to form lipid droplets and store triglycerides. Fat storage-inducing transmembrane protein 2 (FITM2/FIT2) is highly expressed in adipocytes, and data indicate that FIT2 has an important role in the formation of LDs in cells, but whether FIT2 has a physiological role in triglyceride storage in adipose tissue remains unproven. Here we show that adipose-specific deficiency of FIT2 (AF2KO) in mice results in progressive lipodystrophy of white adipose depots and metabolic dysfunction. In contrast, interscapular brown adipose tissue of AF2KO mice accumulated few but large LDs without changes in cellular triglyceride levels. High fat feeding of AF2KO mice or AF2KO mice on the genetically obese ob/ob background accelerated the onset of lipodystrophy. At the cellular level, primary adipocyte precursors of white and brown adipose tissue differentiated in vitro produced fewer but larger LDs without changes in total cellular triglyceride or triglyceride biosynthesis. These data support the conclusion that FIT2 plays an essential, physiological role in fat storage in vivo. 相似文献
35.
Arnau Sans-Dublanc Anna Chrzanowska Katja Reinhard Dani Lemmon Bram Nuttin Théo Lambert Gabriel Montaldo Alan Urban Karl Farrow 《Neuron》2021,109(11):1888-1905.e10
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36.
S. Farrow 《BMJ (Clinical research ed.)》1994,309(6946):1-2
37.
Protease nexin-2/amyloid beta-protein precursor in blood is a platelet-specific protein 总被引:1,自引:0,他引:1
W E Van Nostrand A H Schmaier J S Farrow D B Cines D D Cunningham 《Biochemical and biophysical research communications》1991,175(1):15-21
The protease inhibitor, protease nexin-2 (PN-2), is the secreted form of the amyloid beta-protein precursor (APP) which contains the Kunitz protease inhibitor domain. PN-2/APP is an abundant platelet alpha-granule protein which is secreted upon platelet activation. PN-2/APP mRNA is present in cultured endothelial cells and the protein has been detected in plasma. In the present studies we quantitated PN-2/APP in platelets, plasma and several different cell types of the vasculature to identify the repository of the protein in the circulatory system. We report that PN-2/APP is predominantly a platelet protein in the vascular compartment. Lysates of unstimulated umbilical vein endothelial cells, granulocytes or monocytes contained little PN-2/APP based on sensitive functional protease binding and immunoblotting assays. Quantitative immunoblotting studies demonstrated that normal citrated-plasma contains less than or equal to 60 pM PN-2/APP. In contrast, platelets can contribute up to 30 nM PN-2/APP, indicating that they are the major source of the protein in blood. 相似文献
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