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基于质量作用定律的算法,用于癌症药物发现和开发的具有成本效益的方法。

The mass-action law based algorithm for cost-effective approach for cancer drug discovery and development.

机构信息

Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center New York, NY, USA.

出版信息

Am J Cancer Res. 2011;1(7):925-54. Epub 2011 Aug 5.

Abstract

The mass-action law based system analysis via mathematical induction and deduction lead to the generalized theory and algorithm that allows computerized simulation of dose-effect dynamics with small size experiments using a small number of data points in vitro, in animals, and in humans. The median-effect equation of the mass-action law deduced from over 300 mechanism specific-equations has been shown to be the unified theory that serves as the common-link for complicated biomedical systems. After using the median-effect principle as the common denominator, its applications are mechanism-independent, drug unit-independent, and dynamic order-independent; and can be used generally for single drug analysis or for multiple drug combinations in constant-ratio or non-constant ratios. Since the "median" is the common link and universal reference point in biological systems, these general enabling lead to computerized quantitative bio-informatics for econo-green bio-research in broad disciplines. Specific applications of the theory, especially relevant to drug discovery, drug combination, and clinical trials, have been cited or illustrated in terms of algorithms, experimental design and computerized simulation for data analysis. Lessons learned from cancer research during the past fifty years provide a valuable opportunity to reflect, and to improve the conventional divergent approach and to introduce a new convergent avenue, based on the mass-action law principle, for the efficient cancer drug discovery and the low-cost drug development.

摘要

基于质量作用定律的系统分析,通过数学归纳和演绎,得出了广义理论和算法,允许使用体外、动物和人体中的少量实验数据点进行剂量-效应动力学的计算机模拟。从 300 多个机制特定方程推导出的质量作用定律的中位数效应方程已被证明是一种统一的理论,是复杂生物医学系统的共同联系。在用中位数效应原理作为公分母之后,其应用是机制独立、药物单位独立、动态顺序独立的,可以普遍用于单一药物分析或固定比例或非固定比例的多种药物组合。由于“中位数”是生物系统中的共同联系和通用参考点,这些通用方法使得在广泛的学科领域中可以进行经济绿色生物研究的计算机定量生物信息学。该理论的具体应用,特别是与药物发现、药物组合和临床试验相关的应用,已经以算法、实验设计和计算机模拟的形式被引用或说明,用于数据分析。在过去五十年的癌症研究中获得的经验教训为我们提供了一个宝贵的机会,可以反思并改进传统的发散方法,并基于质量作用定律原则引入一种新的收敛途径,用于高效的癌症药物发现和低成本的药物开发。

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