【摘 要】
：
Statins-inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase-are known to reduce blood cholesterol levels.Statin therapy is regarded as well tolerated,however serious adverse ef
【机 构】
：
Institute of Biochemistry and Biophysics Polish Academy of Science Poland
【出 处】
：
中国上海第七届国际新药发明科技年会
论文部分内容阅读
Statins-inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase-are known to reduce blood cholesterol levels.Statin therapy is regarded as well tolerated,however serious adverse effects have been reported.We have applied a Saccharomyces cerevisiae expression system,which enables the analysis of DNA sequence variations in the context of statin therapy as well as the investigation of the impact of statins treatment on cell lipid metabolism.The sequence of the HMG-CoA reductase gene in DNA extracted from blood samples of patients with cardiovascular disorders was analyzed and a mutated form of the enzyme was found and introduced to the cloned HMG-CoA reductase gene.The yeast and mammalian HMG-CoA reductases demonstrate structural and functional conservation,and expression of human HMG-CoA reductase in yeast complements the lethal phenotype of strains lacking the HMG1 and HMG2 genes.Basing on this finding we exploited the yeast system to examine the sensitivity of the wildtype and mutated versions of the human HMG-CoA reductase to different types of statins.
其他文献
Coenzyme Q 10 (CoQ 10),a lipophilic nutritional supplement,has increased in popularity in many countries because of growing evidence of therapeutic benefits and an excellent safety profile.Improved ce
Physiologically based pharmacokinetic (PBPK) modelling is a simulation tool that has a huge impact in the Lead optimization stage.In PBPK modelling,each tissue is represented as a compartment that has
Building on a previously disclosed PDE4 inhibitor,NVP-ABE171 (1),new compounds were synthesised with significant improvements in physico-chemical properties pharmacokinetics and therapeutic index.Thus
Basic functional groups such as amidines and guanidines are incorporated into various drug candidates and drugs.Because of their basicity,these structures are protonated under physiological conditions
Rabies is still a serious public health problem in the developing countries.It is believed that at least 60,000 human deaths occur each year,and more than 10 million people are reported to receive pos
Tadalafil is a phosphodiesterase-5 inhibitor.It has the disadvantage of poor aqueous solubility.Therefore,it is important to develop an effective method to enhance the solubility of the drug.The aim o
Nanoparticles possess enormous potential as diagnostic imaging agents and hold promise for the development of multimodality agents with both imaging and therapeutic capabilities.Yet,some of the most p
Over the past decade,routine chemistry outsourcing to Asia has given way to full scale drug discovery partnering due in large part to the resettlement of highly skilled,Western trained scientists and
The partnership between Pierre Fabre,a multinational pharmaceutical and cosmetics company,and Pharmaron,a premier drug R&D CRO,has been highly productive and beneficial for both companies.Initially,Pi
As results of restructure and consolidation of global pharma industry,drug discovery outsourcing trends to India and China has been significantly increased in past years and will continue to increase.