American Journal of PharmacoGenomics

A.H. Maitland-van der Zee

S.T. Turner

G.L. Schwartz

A.B. Chapman

O.H. Klungel

E. Boerwinkle

A multilocus approach to the pharmacogenetics of thiazide diuretics

噻嗪类利尿剂的药物基因组学多基因位点研究

High-throughput screening (HTS) is the process of testing a large number of diverse chemical structures against disease targets to identify 'hits'. Compared to traditional drug screening methods, HTS is characterized by its simplicity, rapidness, low cost, and high efficiency, taking the ligand-target interactions as the principle, as well as leading to a higher information harvest. As a multidisciplinary field, HTS involves an automated operation-platform, highly sensitive testing system, specific screening model (in vitro), an abundant components library, and a data acquisition and processing system. Various technologies, especially the novel technologies such as fluorescence, nuclear-magnetic resonance, affinity chromatography, surface plasmon resonance, and DNA microarray, are now available, and the screening of more than 100,000 samples per day is already possible. Fluorescence-based assays include the scintillation proximity assay, time-resolved energy transfer, fluorescence anisotropy, fluorescence correlation spectroscopy, and fluorescence fluctuation spectroscopy. Fluorescence-based techniques are likely to be among the most important detection approaches used for HTS due to their high sensitivity and amenability to automation, giving the industry-wide drive to simplify, miniaturize, and speed up assays. The application of NMR technology to HTS is another recent trend in drug research. One advantage afforded by NMR technology is that it can provide direct information on the affinity of the screening compounds and the binding location of protein. The structure-activity relationship acquired from NMR analysis can sharpen the library design, which will be very important in furnishing HTS with well-defined drug candidates. Affinity chromatography used for library screening will provide the information on the fundamental processes of drug action, such as absorption, distribution, excretion, and receptor activation; also the eluting curve can give directly the possibility of candidate drug. SPR can measure the quantity of a complex formed between two molecules in real-time without the need for fluorescent or radioisotopic labels. SPR is capable of characterizing unmodified biopharmaceuticals, studying the interaction of drug candidates with macromolecular targets, and identifying binding partners during ligand fishing experiments. DNA microarrays can be used in HTS be used to further investigate the expression of biological targets associated with human disease, which then opens new and exciting opportunities for drug discovery. Without doubt, the addition of new technologies will further increase the application of HTS in drug screening and its related fields.

Bailing Liu

Songjun Li

Jie Hu

Am J Pharmacogenomics

Technological Advances in High-Throughput Screening

高通量筛选技术进展

Eating disorders such as anorexia nervosa and bulimia nervosa involve complex and interacting mechanisms. Formal genetic studies suggest that there is a substantial genetic influence for these disorders. Animal models of eating disorders are scarce. Candidate gene studies have initially focused on the serotonergic and other central neurotransmitter systems and on genes involved in body weight regulation. Most of the studies, including meta-analysis, have yielded negative results; only a single positive finding has been replicated independently. Recently, systematic genome-wide scans based on families with two or more individuals with an eating disorder (anorexia nervosa or bulimia nervosa) revealed initial linkage regions on chromosomes 1, 3, and 4 (anorexia nervosa) and 10p (bulimia nervosa). Fine mapping of one of these regions led to the identification of genes where an association with anorexia nervosa was detected. Currently treatment of patients with eating disorders can not rely on results of molecular genetic studies.

Publication Information	Publisher: Adis International Ltd，Publishing cycle: ，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 2001，Proportion of original research papers: ，Self Citation Rate:， Gold OA Rate:

American Journal of PharmacoGenomics

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A multilocus approach to the pharmacogenetics of thiazide diuretics

Technological Advances in High-Throughput Screening

A multilocus approach to the pharmacogenetics of thiazide diuretics

A multilocus approach to the pharmacogenetics of thiazide diuretics

Genetic Risk Factors in Eating Disorders

A multilocus approach to the pharmacogenetics of thiazide diuretics

A multilocus approach to the pharmacogenetics of thiazide diuretics

A multilocus approach to the pharmacogenetics of thiazide diuretics

A multilocus approach to the pharmacogenetics of thiazide diuretics

A multilocus approach to the pharmacogenetics of thiazide diuretics