Abstract LB_B20: The Unity Theory of One: The dynamic algorithm of mass action law for drug and biosimilar digital evaluation/simulation in molecules, cells, and organs, regardless of units, physical states, and mechanisms

Abstract

Abstract Mathematical analysis of mass-action law (MAL) of the intermediate-forming system analysis led to the general median-effect equation (MEE) for action dynamics that determines potency (Dm, median-effect dose, and dynamic order [m, the shape of dose-effect-curve (DEC) where m=1, >1, <1 indicate hyperbolic, sigmoidal and flat sigmoidal, respectively]; the combination index equation (CIE) for interaction that quantifies synergism (CI<1), additive effect (CI=1) and antagonism (CI>1); and the dose-reduction index equation (DRIE) for interaction consequences, where DRI=1, >1 and <1 indicate no dose-reduction, favorable dose-reduction, and unfavorable dose-reduction. All terms of MEE, CIE, and DRIE are dimensionless relativity ratios, thus ensuring the general applicability of MAL. Therefore, the MAL biodynamics, pharmacodynamics, and bioinformatics (MAL-BD/PD/BI) is the top-down fundamental theory-based R&D, which approach is different from the classical observation/statistics-based bottom-up R&D. The MEE, CIE, and DRIE all center on “One” (the Unity Theory of One) (UTO), which are not feasible to derive from the classical specific-aimed derivations, such as Michaelis-Menten, Henderson-Hasselbalch, Hill, Scatchard, and Langmuir equations. The most important extensions and utilities of AML-MEE/CIE are the linearization of DECs with the median-effect plot (MEP) that led to the Minimum Two-dose Data Point Theory (MTDPT), which automatically adds two default data points to DECs (Do, dose-zero, and Dm, the universal reference point and the dynamic-orders common link). Thus, 2 becomes 4, 3 becomes 5, and 4 becomes 6 doses. This discovery allows digital quantitative, simple, efficient, cost-effective, Econo-Green biomedical R&D and drug evaluation of unified regulatory guidance. This MAL-theoretical approach is particularly beneficial in animal studies, clinical trial protocol design, and computerized analysis/simulation. The MAL-theoretical approach (MEE and CIE) was introduced by Chou and Talalay (1984), then by a Review article by Chou (2006) and a Perspective article (2006). Based on the bibliometrics by Web of Science and Google Scholar, as of August 26, 2023, these three articles have been cited 8,020, 5,194, and 5,129 times in 1,523, 1,242, and 1,157 journals internationally. The MAL-BD/PD/CI/BI is an Econo-green complementary alternative to traditional bottom-up studies. The MAL dynamics and informatics have been cited by 1,184 patents and by thousands of research grants sponsored by international governmental institutions, including USA (NIH, NCI, NCATS, NSF, and FDA), EU (Euro. Reginal Develop. Fund), China (Natl Key R&D), Japan (Soc. of Promotion of Sci), Korea (Natl. Sci. Foundation), Germany (Deutsch Fortungsgemeinschaft), France (INSERM), England (MRC), etc. The MAL-BD/PD/CI BI dynamics and informatics provide a new avenue for efficient and cost-effective translational and precision medicine and beyond, including environmental, agricultural, marine, material, biophysical, radiation, and food sciences. Citation Format: Ting-Chao Chou. The Unity Theory of One: The dynamic algorithm of mass action law for drug and biosimilar digital evaluation/simulation in molecules, cells, and organs, regardless of units, physical states, and mechanisms [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_B20.