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| 1 | 基于G-蛋白偶联受体激酶2抑制剂治疗心力衰竭的合理药物设计(英文)显示文摘G protein-coupled receptors(GPCRs)convert extracellular stimuli in the form of hormones,odorants and light into profound changes in cell homeostasis.Their timely desensitization is critical for cells to rapidly respond to changes in their environment and to avoid damage from sustained signaling.Seven GPCR kinases(GRKs)phosphorylate and regulate the activity of most of the^800 GPCRs in the human genome.Although GRKs normally play an adaptive role,in conditions such as chronic heart failure they are overexpressed and linked to disease progression.GRK2 and GRK5 have thus become important targets for the treatment of heart failure and pathological cardiac hypertrophy,respectively.Our lab has determined atomic structures representing all three vertebrate GRK subfamilies,and is now in the midst of a campaign to develop selective inhibitors of these enzymes using structure-based rational design.We have identified the FDA approved drug paroxetine as a selective GRK2 inhibitor,determined the crystal structure of the GRK2·paroxetine complex and,in collaboration with the Koch lab,showed that the drug improves contractility in myocytes and,most impressively,recovery in postmyocardial infarcted mice.Since then,we have identified additional chemical scaffolds that exhibit even higher potency and/or selectivity for GRK5.Using a'hybrid'inhibitor design approach we have generated GRK selective chemical probes that exhibit improved potency and stability and are able to increase inotropy and dampen the hypertrophic response in cardiomyocytes and small animal models.Structural analysis has revealed the molecular basis for selectivity and potency in many of these compounds,allowing for the design of future generations of GRK chemical probes. | John J TESMER Helen V WALDSCHMIDT Marie C CATO Renee BOULEY Osvaldo CRUZ-RODRIGUEZ Scott D LARSEN | 2017 | 中国药理学与毒理学杂志2017，31，10： | 1 |
| 2 | Mapping of bovine skeletal muscle proteins using two-dimensional gel electrophoresis and mass spectrometry显示文摘 | Bouley J Chambon C Picard B | 2004 | Proteomics2004，4，6： | 1 |
| 3 | Proteomic analysis of bovine skeletal muscle hypertrophy 显示文摘 | Bouley J Meunier B Chambon C | 2005 | Proteomics2005，5，2： | 1 |
| 4 | Functional food Science and Gastrointestinal Physiology and Function显示文摘 | SALMINEN S BOULEY M C BOUTRON-RUALT M C | 1998 | Br J Nutr Suppl1998，1，： | 1 |
| 5 | Mapping of alkaline proteins in bovine skeletal muscle显示文摘 | Chaze T Bouley J Chambon C | 2006 | Proteomics2006，6，8： | 1 |
| 6 | Functional food science and gastrointestinal physiology and function显示文摘 | Salminen S C Bouley M C Boutron-Ruauh | 1998 | Br J Nutr1998，80，： | 1 |
| 7 | Functional food science and gastrointestinal physiology and function 显示文摘 | Salminen S Bouley C Boutron-Ruault M C | 1998 | BrJNutr1998，80，1： | 1 |
| 8 | Mapping of bovine skeletal muscle proteins using two-dimensional gel electrophoresis and mass spectromety显示文摘 | Bouley J Chambon C Picard B | 2004 | Proteomics2004，4，6： | 1 |
| 9 | Functional food science and gastrointestinal physiology and function显示文摘 | SALMINEN S BOULEY C BOUTRON-RUAUT M C | 1998 | Br J Nutr1998，80，1： | 1 |
| 10 | Functional food science and gastrointestinal physiology and function显示文摘 | Salminen S Bouley C Boutron R M C | 1998 | Br J Nutr1998，80，1： | 1 |
| 11 | functional food science and gastrointestinal physiology and function显示文摘 | Salminen S Bouley C Boutron Ruauh M C | 1998 | Br J Nutr1998，80，1： | 1 |
| 12 | Colonic microflora:nutrion and heath: summary and conclusions of an International Life Sciences Institute (ILSI) (Europe) workshop held in Barcelona, Spain 显示文摘 | ROBERFROID M B BORNET F BOULEY C | 1995 | Nutr Rew1995，53，： | 1 |
| 13 | Mapping of bovine skeletal muscle proteins using two-dimensional gel electrophoresis and mass spectrometry显示文摘 | BOULEY J CHAMBON C PICARD B | 2004 | Proteomics2004，4，6： | 1 |
| 14 | Proteomic analy- sis of bovine skeletal muscle hypertrophy 显示文摘 | Bouley J Meunier B Chambon C | 2005 | Pro- teomics2005，，5： | 1 |
| 15 | Inhibitory Effect of Dairy Products on the Mutagenicities of Chemicals and Dietary Mu- tagens显示文摘 | CASSAND P ABDELALI H BOULEY C | 1994 | Journal of Dairy Research1994，61，4： | 1 |
| 16 | Cell surface characteristics of Lactobacillus casei subsp,casei,Lactobacillus paracasei subsp,paracsei,and Lactobacillus rhamnosus strains显示文摘 | Bouley C Cayuela C el al | 1997 | Appl Environ Microbiol1997，63，5： | 1 |
| 17 | Proteomic analysis of bovine skeletal muscle hypertrophy 显示文摘 | Bouley J Meunier B Chambon C | 2005 | Proteomics2005，5，2： | 1 |
| 18 | Proteomic analysis of bovine skeletal muscle hypertrophy显示文摘 | Bouley J Meunier B Chambon C | 2005 | Proteomics2005，5，2： | 1 |
| 19 | Proteomic analysis of bovine skeletal muscle hypertrophy显示文摘 | Bouley J Meunier B Chambon C | 2005 | Proteomics2005，5，2： | 1 |
| 20 | Functional food science and gastrointesti- nal physiology and function 显示文摘 | SALMINEN S BOULEY C BOUTRON-RUAULT M C | 1998 | Br J Nutr1998，80，1： | 1 |
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