Review of Present Trends and Future Scope of Pharmacogenomics in Drug Discovery and Development Process

V. Chandrakala, U. Sanki
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引用次数: 1

Abstract

Pharmacogenomics combines traditional pharmaceutical sciences such as biochemistry with annotated knowledge of genetics, protein chemistry, and DNA polymorphisms. The difference of therapeutic efficacy of the same drug in different individual can be best explained by the study of genetic polymorphisms that underlie individual differences in drug response. The small change of the genome in one individual may make a drug inefficacious as oppose to the other patients. Such variability will bring the individualization of the therapy to obtain the best effects of the drug, as an example autologous dendrimer got a tremendous success in the cancer therapy of the individual. Markers of exposure can determine whether the desired target tissues of a subject have been exposed to a drug at physiological concentrations. Gene expression profiling is a tool that can be used to characterize chemically induced toxicity in cells and/or animal models, in order to provide plausible explanations for observed toxicity in preclinical testing. Pharmacogenomics holds the promise that drugs might one day in future be tailor-made for individuals and adapted to each person's own genetic makeup by the use of microarray technology to express the gene which in turn helps to develop receptor protein. The stability of the drug and its toxicity can be predicted prior to administration of the drug to the subject through the knowledge of computer assisted structural simulation and DNA reactivity technology respectively. This article provides some critical aspects of drug developments, clinical trial design and ethical issues which are centered with pharmacogenomics.
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药物基因组学在药物发现和开发过程中的发展趋势和前景综述
药物基因组学结合了传统的制药科学,如生物化学与遗传学、蛋白质化学和DNA多态性的注释知识。同一种药物在不同个体的治疗效果差异可以通过研究药物反应个体差异的遗传多态性来最好地解释。一个人基因组的微小变化可能会使药物对其他病人无效。这种可变性会带来个体化治疗以获得药物的最佳效果,例如自体树突状分子在个体癌症治疗中取得了巨大成功。暴露标记可以确定受试者的目标组织是否暴露于生理浓度的药物。基因表达谱是一种工具,可用于表征细胞和/或动物模型中化学诱导的毒性,以便为临床前试验中观察到的毒性提供合理的解释。药物基因组学有望在未来的某一天为个人量身定制药物,并通过使用微阵列技术来表达基因,从而帮助开发受体蛋白,从而适应每个人自己的基因组成。通过计算机辅助结构模拟和DNA反应技术的知识,可以在给药之前预测药物的稳定性和毒性。本文介绍了以药物基因组学为中心的药物开发、临床试验设计和伦理问题的一些关键方面。
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