CompuSyn for Drug Combinations
and for General Dose-Effect Analysis
by Ting-Chao Chou
Memorial Sloan-Keltering Cancer Center
New York, NY
Massachustts Institute of Technology
Published for PC windows in 2005 by: ComboSyn, Inc., Paramus, NJ. 07652 USA
A Computer Program for PC Windows (Not for Mac)
For Single Drug and Drug Combinations Pharmacodynamics with Automated Simulations
For Dose-Effect Data Analysis from Enzymes, Receptors, Microorganisms, Cells, Animals and Clinical Trials
Also for Determination of:
IC50 IC95 ED50 LD10 LD50 ICx EDx LDx
CompuSyn General Features
New, Easy, Versatile, Automation, and Quantitation of Synergism and Antagonism; Mass-Action Law Based.
- Automated Construction of Dose-Effect Curve
- Automated Construction of Isobologram
- Automated Determination of Combination Index (CI) and Dose-Reduction Index (DRI)
- Automated Generation of Fa-CI Plot and DRI Plot
- Automated Determination of IC50, IC90, ED50, ED90, LD50, etc.
- Data Storage and Retrieval
- Color Graphics, Flexible Scale
- Editing and Transport of Data for strage and Retrieveal for Report
- User’s Guide for background, theoretical basis, illustration and sample analysis
- Small Size Experimentation, Requires Few Data Points for Single Drug or Combinations
- Can be Used for Constant or Non-Constant Ratio Drug Combination Design
- Schedule Dependency of Drug Combination
- Drug Combination Graphics at constant ratio (preferred) or at non-constant ratios
Easy, Versatile, Automative, and Quantitative
- Generate Figures, Tables, Plots and Summary in about one second after data entries
- Dose-Effect Curve and its linearization with the Median-Effect Plot
- Combination Index (CI) table and plot
- Dose-Reduction Index (DRI) table and plot
- Isobologram at any selected effect level (default at ED50, ED75 and ED90)
- Polygonogram for more than two drug combinations for semiquantitative visual inspection or projection of outcomes
B. Synergism and Antagonism
Computerized Simulation, Quantitation and Graphics
Based on the Median-Effect Principle (Chou) and the Combination Index-Isobologram Theorem (Chou-Talalay). Used in over 8,000 scientific papers.
For Details, see: Chou TC, Pharmacological Reviews 58: 621-681, 2006.
Free web link: http://pharmrev.aspetjournals.org/content/58/3/621; doi:10.1124/pr.58.3.10
C. Popularity and Broad Applications:
Based on Thomson Reuters Web of Science (www.researcherid.com/rid/B-4111-2009) and Google Scholar Citations (Ting Chao Chou), the median-effect equation and plot (Chou), and the combination index equation and plot (Chou-Talalay) have been cited in over 10,000 scientific papers published in over 850 different biomedical journals. Applied to in vitro and in vivo data, single drug analysis or combinations up to seven drugs.
D. Important Notes for First-Time Users
A typical 2-drug combination in vitro at a constant ratio combination usually uses only 16 data points for dose and effect, e.g., 5 concentrations for each drug, and their combination, and an uninhibited control, for the constant ratio at or near (IC50)1/(IC50)2 ratio, via "2-fold serial dilutions" in a diagonal scheme. The experiment with six or more concentrations each would be more desirable if the proper concentration-range is not known. All in vitro assays are carried out on the same day under standardized conditions, and usually in duplicate or triplicate and only the average effect values (fa's) for each concentrations were used for the dose-effect data entries into computer for automated computerized analysis. The manual inputs of Experimental Title, Date, Drug Names (including Abbreviations), and Experimental Data may take 10 min; Computerized Simulation may take 1-2 seconds; the print-out time and saving the file may take 2 minutes. Usually drug combination experiments in vitro take one to two weeks to complete. The 15 minute data and information entry is minor essential effort for the study, and it provides the opportunity to inspect and to delete the extremely low effect or extremely high effect data points which are beyond the accuracy of the assay. Do not enter unreliable data into computer for data analysis. The negative fa value , or fa=0 or fa=1 would cause the analysis to crash. The r value of the median-effect plot will show how good is your data with r=1 indicating perfect. Usually fa>0.95 (in vitro) and fa>0.92 (in vivo) are considered acceptable.
The best way to learn the applications of the Chou-Talalay CI method is to read the Examples of real data analysis given in the last section of this website. More detail information is available in the Chou, T.C. Supplemental Appendices in Pharmacol. Rev. 58:621-681, 2006.