Abstract 5526: Mass-action law algorithm-based computer simulation for efficient and econo-green cancer drug discovery and development.

Abstract

Abstract Physico-chemical principle of the mass-action law algorithm (MALA) is the basis for systematic pharmacodynamics (PD) that leads to general median-effect equation (MEE) for single entity effect and the combination index equation (CIE) for multiple entity interactions (Chou TC, Pharmacol. Rev. 58: 621-681, 2006; Free web access: http://pharmrev.aspetjournals.org/content/58/3/621). “Median” is the common-link and universal reference point for single and multiple entities and for 1st-order and higher-order dynamics. Median is also the harmonic mean of kinetic constants where the harmony is the state of pure non-competitiveness [Chou, Nature Precedings (npre.2008.2064-2). Available free at http://precedings.nature.com/documents/2064/version/2]. Based on MEE, all dose-effect curves whether hyperbolic or sigmoidal, weak or strong, 1st-order or higher-order, in vitro or in vivo, can be linearlized by the median-effect plot with small number of data points in small size experiments (Chou, J. Theor. Biol. 59: 253-276, 1976; Pharmacol. Rev. .ibid). Based on CIE, CI<1, =1, and >1 quantitatively indicates synergism, additive effect, and antagonism, respectively (Chou & Talalay, Adv. Enz. Regul. 22: 27-55, 1984; Cancer Res. 70: 440-446, 2011). Thus. MEE is the common denominator for simple and complex bio-systems in vitro, in animal and in clinics. Computerized simulation of MEE or CIE can take <1 second, and the graphics can be drawn automatically (CompuSyn, www.combosyn.com, Free download). Applying this theory in this author's laboratory (personnel < 5 for decades) has published 253 articles that have been cited 13,749 times in over 523 different biomedical journals with h-index of 55 (Thomson Reuters Web of Science, www.researcherid.com/rid/B-4111-2009) along with 30 US patents. Thus, MALA-PD theory is the common denominator for integrating complex bio-systems and its computerized simulation have proven to lead to efficient, quantitative and econo-green bio-research and new drug discovery and development as illustrated in Chou, Integr. Biol. 3: 548-559, 2011; DOI: 10.1039/c0ib00130a and in Am. J. Cancer Res. 1(7): 925-954, 2011, Free web access: www.ajcr.us. Citation Format: Ting-Chao Chou. Mass-action law algorithm-based computer simulation for efficient and econo-green cancer drug discovery and development. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5526. doi:10.1158/1538-7445.AM2013-5526 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.