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Welcome to ComboSyn, Inc.

ComboSyn, Inc., the publisher of CompuSyn software [1], was set up by Dr. Dorothy Chou in 2005 with the purpose of promoting pharmacodynamic research and simple computerized analytical simulation using the median-effect principle of the mass-action law [2,3] and its combination index theorem [3,4].

ComboSyn, Inc. always has a vision of not–for–profit purposes. Therefore, upon the recovery of the software developmental expense and administration cost, the company announced on August 1st, 2012, that as a contribution to the bio-medical research communities, the CompuSyn software would offer for free download without cost upon registration and adherence to the original terms of usage as indicated in the inner cover of the User's Guide. Researchers who are interested and agree with the terms are welcome to register and download theCompuSyn software along with its User’s Guide free of charge. In 2013, the PD Science LLC was established by Ting-Chao Chou, the initiator of the mass-action law pharmacodynamics theory (MAL-PD) and co-developer algorithm of the CompuSyn software, to take care of scientific affairs related to MAL-based research and development of the ComboSyn, Inc. As of June 2023, there are 51,990 downloads by scientists from 137 countries or territories.

The unique mathematical system analysis of the mass-action law (MAL) with sequential, combinatory, pattern analysis and mathematical induction-and-deduction for dose-effect dynamics during 1966-1976 led to the discovery of the median-effect equation (MEE) as the unified biodynamics, pharmacodynamics, and general bioinformatics principle (BD/PD/BI). The parameter m is the dynamic-order signifying shape of the dose-effect curve; Dm is the median-effect dose signifying potency, the universal reference point, and the common link for different dynamic orders. The dynamics of the multiple entities interactions dynamics resulted in the general combination index equation (CIE), algorithm, and computer simulation which quantitatively determine “Synergism (CI <1), additive-effect (CI=1) and antagonism (CI>1) automatically. All terms of MEE and CIE are dimensionless relativity ratios, thus allowing universal applicability.

The MAL general theory/algorithm for functional dose-effect dynamics can generally be applied in vitro, in vivo, and in all physical states (in nanoparticles, cells, tissues, organs, animals, humans, diseases, clinical trials, and in environments); in drugs, biologics, radiation, ultraviolet, microwave, thermo-dynamics, and photo-dynamics. This MAL integrated unified “Top Down” theory/method is easily distinguishable from the traditional observation-based “Bottom Up” approach where a specific aim, selected method, and statistical evaluations were performed.

The MAL-BD/PD/CI/BI functional dynamics unified theory-based “Top Down” algorithm allows using a few (two or more) dose-data points (where the MEE algorithm automatically adds “dose zero” and “the median-effect dose” (Dm) as a universal reference-point, by default, to fit all dose-effect dynamics analysis. Thus, the MAL approach has the features of efficiency, cost-effectiveness, and automated quantitative simulation. By contrast, traditional observation-based biomedical research is mainly the “Bottom Up” approach with a specific aim, proposed or selected method for findings, unbiased statistical data analysis, then reaching a hypothesis or conclusions. The traditional concept usually uses many dose-data points to fit empirical curves or empirical formulas that have no physical or chemical bearings and rely heavily on statistical analysis or selected methods for conclusions. It is shown that the theoretical “Top Down” and the observational “Bottom Up” approaches are conceptually opposite, yet proven to be complementary alternatives to each other in R&D, like two sides of the same coin or the front and rear views on the same entity.

As of June 27, 2023, the MAL-MEE/CIE theory has been cited over 22,992 times in over 1,515 scientific journals covering pharmacology, cancer research, biochemistry, molecular, cell biology and genetics, drug evaluation and therapeutics design, toxicology, agricultural, marine, environmental and food sciences. Most significantly the Web of Science database showed that the MAL unified general theory/method is cited in 1,175 patents, indicating a high impact on scientific innovation and drug discoveries. Its applications encompass a broad spectrum of biomedical and other sciences, and the subjects include drugs, chemicals, biologicals, and materials, regardless of units, modes, or mechanisms of actions and the physical states. Recently, the applications of MAL-PD/BD/BI and CI have been extended to radiation, signaling, photo-effects, thermodynamics, UV, and microwave, as well as the anti-microbial, anti-HIV, anti-SARS-CoV-2 drug evaluations. Currently, the most widely used aspects are interaction dynamics of drug-drug, drug-entity, or entity-entity using the CI quantitative computer simulations, and single drug or single entity for the MAL-basic dynamic parameters, m (shape, or dynamic-order) and Dm (potency, or dynamic order-common-link), for digital determination of PD basic properties of actions and informatics, and for the unified ranking of drugs or entities, and their combination interaction dynamics. The MAL principle does not emphasize “big data” size or statistics but focuses on proper small experimental MAL-PD/BD “design” for useful and digital “data quality” for efficient and cost-effective dynamics and informatics, with MAL-algorithm-based automated computer simulations.

The pulldown sections of this website provide general information, video demos, and illustrated examples of applications in vitro, in animals, and in clinical trials. More details are available below in the illustrative PFD slides for MAL-BD/PD/CI/BI theory, MAL-based experimental design, and examples of specific applications. The last section provides the categorized application references during 2020-2023.

For any questions, please see the illustrations of the pull-down menu.

Best wishes on your scientific endeavors.

ComboSyn, Inc.

PD Science, LLC., June 27, 2023

Other Websites: Google Scholar Citations – Ting-Chao Chou,

For total Citing-Journals: Web of Science Database : or


Wikipedia – Ting-Chao Chou; Altmetrics ting-chao chou

Selected Representative References

A. MAL-BD/PD/CI/BI Theory and Reviews:

  1. Chou T, Martin N. CompuSyn software. CompuSyn for drug combinations: PC software and user’s guide: a computer program for quantitation of synergism and antagonism in drug combinations, and the determination of IC50 and ED50 and LD50 values. ComboSyn Inc., Paramus, NJ. 2005. (Website for registration and free download)
  2. Chou TC. Derivation and properties of Michaelis-Menten type and Hill type equations for reference ligands. J Theor Biol. 1976;59(2):253-276.[Cited 426 times]
  3. Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul. 1984;22:27-55. [Cited 8,015 times in over 1,515 journals]
  4. Chou TC. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev. 2006;58(3):621-681. [Cited 5,115 times in over 1,230 journals]
  5. Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 2010;70(2):440-446. [Cited 5,037 times in 1,143 journals]
  6. Chou T-C. The mass-action law-based algorithms for quantitative econo-green bio-research. Integrative Biology. 2011;3(5):548-559.
  7. Chou, TC. The mass-action-law based GPS concept for bio-informatics. Nat Prec. 2008.
  8. Chou T-C. Frequently asked questions in drug combinations and the mass-action law-based answers. Synergy. 2014;1(1):3-21.
  9. Chou T-C. The median-effect principle and the combination index for quantitation of synergism and antagonism. In: Chou TC, Rideout DC, editors. Synergism and Antagonism in Chemotherapy: Academic Press, Inc. San Diego, New York, Boston, London; 1991. p. 61-102. ISBN 0-12-174090-0.
  10. Chou TC, Motzer RJ, Tong Y, Bosl GJ. Computerized quantitation of synergism and antagonism of taxol, topotecan, and cisplatin against human teratocarcinoma cell growth: a rational approach to clinical protocol design. J Natl Cancer Inst. 1994;86:1517-1524.[Cited 611 times in 291 journals]
  11. Chou TC. Preclinical versus clinical drug combination studies. Leuk Lymphoma. 2008; 49(11):2059-2080.
  12. Chou TC, Talalay P. Analysis of combined drug effects: a new look at a very old problem. Trends Pharmacol Sci. 1983; 4:450-454.[Cited 692 times]
  13. Chou T-C. The combination index (CI < 1) as the definition of synergism and of synergy claims. Synergy. 2018;7:49-50.
  14. Chou T-C. The mass-action law-based algorithm for cost-effective approach for cancer drug discovery and development. American journal of cancer research. 2011;1(7):925.
  15. Chou TC. Relationships between inhibition constants and fractional inhibition in enzyme-catalyzed reactions with different numbers of reactants, different reaction mechanisms, and different types and mechanisms of inhibition. Mol Pharmacol. 1974;10:235-247. PMID: 4212316
  16. Chou TC, Chou JH. Determination of availability of ligand binding site at steady state for topological assessment of receptors with the aid of microcomputers. Eur J Pharmacol. 1990; 183:921. (Abstract)
  17. Chou TC, Talalay P. A simple generalized equation for the analysis of multiple inhibitions of Michaelis-Menten kinetic systems. J Biol Chem. 1977; 252:6438-6442. PMID: 893418
  18. Chou TC, Talalay P. Generalized equations for the analysis of inhibitions of Michaelis-Menten and higher-order kinetic systems with two or more mutually exclusive and nonexclusive inhibitors. Eur J Biochem. 1981; 115:207-216.[Cited 515 times]
  19. Chou TC. Combinatorial analysis of multiple substrate-multiple product enzyme reactions. J Theor Biol. 1972;35:285-297.
  20. Chou TC. On the determination of availability of ligand binding sites in steady-state systems. J Theor Biol. 1977;65:345-356.

B. MAL-BD/PD/CI/BI Recent Abstracts, Editorial and Commentary:

  1. Chou TC. Mass-action law dynamic theory/algorithm based top-down general bioinformatics. Am. Soc. Biochem. Mol. Biol. 2023 Annual Meeting. Discover BMB-2023. Seattle, WA. Journal of Biological Chemistry 2023;299(3):S201. Abstract No 1195.
  2. Chou TC. Mass-action law dynamic theory-based “top-down” approach with observation/statistics-based “bottom-up” approach for bioinformatics in biomedical R&D. Am. Soc. Pharmcol. Exp. Ther. 2023 Annual Meeting. St. Louis, MO. J. Pharmacol. Exp. Ther. 385, June 2023
  3. Choudhary A, Calianese D, Honnen W, Kolloli A, Dikdan RJ, Jaijyan D, Song G, Capozzola T, Sy C, Akkaraju V, Mattappallil A, Rosania A, Khan S, Lerman M, Nikaein A, Subbian S, Chou TC, Andrabi R, Burton D, Pinter A. Broad-spectrum heavily mutated monoclonal antibody isolated from COVID-19 convalescent vaccinee with capacity to neutralize SARS-CoV2 variants ranging from B.1 to BQ.1.1. May 2023. (see bioRxiv 2023.05.04.539267.
  4. Chou TC. Functional Biodynamics Theory and Algorithms for Inhibitor or Activator Effectors and Their Interactions, by Computer Simulation Bioinformatics for Translational Medicine. The FASEB Journal. 2022
  5. Chou TC. MAL-pharmacodynamics theory based small-size experimental-design and analysis, in vitro, in animals and in clinical trial, with bioinformatics algorithm, for automated computer simulation to achieve quantitative/digital/indexed conclusions. The FASEB Journal. 2022; 36 (S1).
  6. Chou TC. Mathematical definitions of “additive effect of two (or more) drugs” and their synergism and/or antagonism based on mass‐action law (MAL) algorithms for pharmacodynamics (PD), biodynamics (BD) and bioinformatics (BI) simulations. The FASEB Journal. 2022; 36 (S1).
  7. Chou TC. New Paradigm, Equations, Algorithm, and Computer software of Mass‐action Law Based Biodynamics, Pharmacodynamics and Bioinformatics (MAL‐BD/PD/BI) for Econo‐Green Biomedical R&D and Regulatory Guidance. The FASEB Journal. 2021; 35(S1).
  8. Chou TC. Why drug and radiation combination synergism or antagonism can be quantitatively determined with the mass-action law-based pharmacodynamics equation, algorithm and computer simulation. Video abstract. Conference: Abstracts: AACR Virtual Special Conference on Radiation Science and Medicine; March 2-3, 2021. Clin Cancer Res (2021) 27 (8_Supplement): PO-062.
  9. Chou TC. What is synergy? Scientist. 2007;21:15. (Letter to the editor)
  10. Chou T-C. Drug combinations: from laboratory to practice. The Journal of laboratory and clinical medicine (An editorial). 1998;132(1):6-8.

C. MAL-BD/PD/CI/BI Applications: Drug Discoveries, Exploration in Vitro, in Animals, and in Clinical Trials:

  1. Zhang N, Fu JN, Chou TC. Synergistic combination of microtubule targeting anticancer fludelone with cytoprotective panaxytriol derived from panax ginseng against MX-1 cells in vitro: experimental design and data analysis using the combination index method. Am J Cancer Res. 2016;6(1):97-104. PMID: 27073727
  2. Baba TW, Liska V, Hofmann-Lehmann R, Vlasak J, Xu W, Ayehunie S, et al. Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian–human immunodeficiency virus infection. Nature medicine. 2000;6(2):200-206.
  3. Vogt MW, Hartshorn KL, Furman PA, Chou TC, Fyfe JA, Coleman LA, et al. Ribavirin antagonizes the effect of azidothymidine on HIV replication. Science. 1987;235(4794):1376-1379.
  4. Doello K, Mesas C, Quiñonero F, Rama AR, Vélez C, Perazzoli G, Ortiz R. Antitumor effect of traditional drugs for neurological disorders: preliminary studies in neural tumor cell lines. Neurotoxicity Research. November 30, 2022
  5. Grbovic-Huezo O, Pitter KL, Lecomte N, Saglimbeni J, Askan G, Holm M, Melchor JP, Chandwani R, Joshi S, Haglund C, Iacobuzio-Donahue CA, Chiosis G, Tammela T, Leach SD. Unbiased in vivo preclinical evaluation of anticancer drugs identifies effective therapy for the treatment of pancreatic adenocarcinoma. Proc Natl Acad Sci USA. 2020;117(48):30670-30678.
  6. Riether C, Pabst T, Höpner S, Bacher U, Hinterbrandner M, Banz Y, Müller R, Manz MG, Gharib WH, Francisco D, Bruggmann R, van Rompaey L, Moshir M, Delahaye T, Gandini D, Erzeel E, Hultberg A, Fung S, de Haard H, Leupin N, Ochsenbein AF. Targeting CD70 with cusatuzumab eliminates acute myeloid leukemia stem cells in patients treated with hypomethylating agents. Nature Medicine. 2020;26:1459–1467.
  7. Lacoangeli A, Marcatili P, Deane C, Lesk AM, Pastore A, Teichmann SA (2022). Editorial: A journey through 50 years of structural bioinformatics in memoriam of Cyrus Chothia. Frontiers in Molecular Biosciences. 2022;9(885318).
  8. Astrinidis A, Li C, Zhang EY, Zhao X, Zhao S, Guo M, Olatoke T, Mattam U, Huang R, Zhang A, Pitstick L, Kopras EJ, Gupta N, Jandarov RA, Smith EP, Fugate E, Lindquist D, Markiewski MM, Karbowniczek M, Wikenheiser-Brokamp KA, Setchell KD, McCormack FX, Xu Y, Yu J. Upregulation of acid ceramidase contributes to tumor progression in Tuberous Sclerosis Complex. JCI Insight. 2023;e166850.
  9. Ali AA, Cairns LV, Clarke KM, Blayney JK, Lappin KM, Mills KI. Combination therapies targeting apoptosis in paediatric AML: Understanding the molecular mechanisms of AML treatments using phosphoproteomics. International Journal of Molecular Sciences. 2023;24(6):5717.
  10. Fu J, Zhang N, Chou JH, Dong H-J, Lin S-F, Ulrich-Merzenich GS, et al. Drug combination in vivo using combination index method: Taxotere and T607 against colon carcinoma HCT-116 xenograft tumor in nude mice.Synergy. 2016;;3(3):15- 30.
  11. Mildvan D, Bassiakos Y, Zucker ML, Hyslop Jr N, Krown SE, Sacks HS, et al. Synergy, activity and tolerability of zidovudine and interferon-alpha in patients with symptomatic HIV-1 infection: AIDS Clinical Trial Group 068.Antiviral therapy. 1996;1(2):77-88. PMID: 11321183
  12. Chou J, Chou T. Computerized simulation of dose reduction index (DRI) in synergistic drug combinations. Pharmacologist. 1988;30:A231. (Abstract)
  13. Chou T-C. The combination index (CI < 1) as the definition of synergism and of synergy claims. Synergy. 2018;7:49-50.
  14. Chou TC. Drug combination synergy quantification in animals and clinics using computerized combination index method. April 2010; Cancer Research 70(8 Supplement): 5398-5398.

D. Recent References for MAL-BD/PD/CI/BI Applications: Translational Informatics from Biochemical, Agricultural, Environmental Sciences, to AI and Machine Learning (mainly 2020 – 2023)
[See the last section “Categorized Application References” of this website]