Is there a free software for calculation of combination index for 2 anticancer drugs? Alternatively, how to do it manually to conclude that there is synergistic effect?
Actually, as of Aug 1st the answer is yes !! The company ComboSyn ( here http://www.combosyn.com/ ) is giving away the software, CompuSyn, for free to academics. It is based on the same Chou-Talalay’s Combination Index Theorem that CalcuSyn is based on. It is for PC and requires Java.
There is a brief registration, and then its all yours !!
Compusyn makes very easy your drug combined effect data analysis, but the main pre-requisite is conformity of your crude data to mass action law. So you have to make sure that the r values you get for your data are acceptable (ie > 0.95 for in vitro tests).
If the drugs you study have an individual sigmoid pattern of dose response curve, you can use the 'mixlow' package which run under R programming language environment.
Please follow the link :
http://cran.r-project.org/web/packages/mixlow/index.html
CI=(D)1/(Dx)1+(D)2/(Dx)2+ alpha(D)1(D)2/(DX)1 (Dx)2.....
where (Dx)1= dose of drug 1 to produce 50% cell kill alone; (D)1=
dose of drug 1 to produce 50% cell kill in combination with (D)2;
(Dx)2= dose of drug 2 to produce 50% cell kill alone; (D)2= dose of
drug 2 to produce 50% cell kill in combination with (D)1; anda= 0 for
mutually exclusive or 1 for mutually nonexclusive modes of drug
action. CI > 1.3 indicates antagonism, CI = 1.1 to 1.3 moderate
antagonism, CI = 0.9 to 1.1 additive effect, CI = 0.8 to 0.9 slight
synergism, CI = 0.6 to 0.8 moderate synergism, CI = 0.4 to 0.6
synergism, and CI = 0.2 to 0.4 strong synergism.
I have two questions please clarify me
1. what is mutually exclusive or 1 for mutually nonexclusive modes of drug
action
2. If one drug having no IC50 value how to calculate Combination Index.
The website seems to be experiencing issues, the download page is not working today. Anyone has tried to download and install Compusyn lately?
The website seems to be experiencing issues, the download page is not working today. Anyone has tried to download and install Compusyn lately?
The website seems to be experiencing issues, the download page is not working today. Anyone has tried to download and install Compusyn lately?
Dear Biomedical Researchers:
I am Ting-Chao Chou, the originator of the Mass-Action Law based Pharmacodynamics (PD), Biodynamics (BD) and Bioinformatics (BI), i.e., MAL-PD/BD/BI. This included the median-effect equation (MEE, 1976), now called the Unified Theory or the Doctrine of the Median (Chou,TC. Pharmacol. Rev. 58: 621-681, 2006, which has been cited 3,031 times in 914 biomedical journals). The extension of MEE led to the Comnination Index Equation (CIE, 1984), which quantitatively determine synergism (CI1), respectively. The original article introducing the theory, equation, algorithm and computer software in Chou TC and Talalay P, Adv. Enz Regul 22: 27-55, 19840 has been cited 6,195 times in 1,249 journals worldwide. The web site, www.combosyn.com has Users' Guide, descriptions, illustrations , references, slides and video presentations, and explained with specific real data examples. There are over ten reviews, perspectives or Q&S papers available. (see Google Scholars Citations - Ting-Chao Chou, or Web of Science or Publons). The CompuSyn software was on market 2014-2012 at $399/software, is offered for free download beginning 8.1.2012, upon registration, as the donations to the biomedical and pharmaceutical communities. As of 7.25.2019, there are 34,425 downloads by scientists in 129 countries or territories.
The MEE took 10 years to develop, and CIE took 7 years to develop, it is not easy to explain in a few sentences. The users need to read articles and visit the web site. Sorry, I cannot respond to most inquiries to the CI method. Please work with your colleagues for help. Thank you.
To update the MAL-PD/BD/BI theory and the CI method, I am attaching a set of 43 PDF slides for your information.
Sincerely yours,
Ting-Chao Chou, Ph.D. (Yale'70)
-------------------------------------------------------------
Actually, as of Aug 1st the answer is yes !! The company ComboSyn ( here http://www.combosyn.com/) is giving away the software, CompuSyn, for free to academics. It is based on the same Chou-Talalay’s Combination Index Theorem that CalcuSyn is based on. It is for PC and requires Java
How to calculate combination index has been described in numerous papers and review articles by T.C. Chou. The CI calculation has been reported or cited in over 10,000 papers. It’s calculation can be greatly helped by calculators, or especially by ConpuSyn by Chou & Martin. It was on market 2005 to 2012 for $399 per software. On August 1， 2012， CompuSyn was donated to biomedical communities upon registration and agree to indicated guidelines and restrictions. It is not a give away . The earlier version of software, CalcuSyn, (
by T.C. Chou & Mike Hayball) can be obtained by purchase order from Biosoft, Cambridge, UK. , $300 for single user license. Answered by Ting-Chao Chou. On 1. 19. 2020.
If you were interested, also look at this link and the Compusyn software tutorial.
Book Tech Talks. Drug Combinations Synergism or Antagonism Compus...
Dear Dr. Darvin,
To understand it, you can use Combenefit tool (https://www.cruk.cam.ac.uk/research-groups/jodrell-group/combenefit). It's free and easy to use.
Combenefit does not mass-action law (MAL) nor Pharmacodynanics (PD) principle, I can see how it can quantification of synergism or antagonism? The basic requirement is to define "What is the "additive effect" of two drug or n drugs? Attached illustrative 46 PDF slides would summary my points. I hope they are useful to you.
T.C. Chou, Founder of PD Science LLC, since 2013.
10.13.2021 Chou TC Comments on PD and CI:
Several basic comments on MAL-PD/CI: 1. Chou's Median-effect eq [MEE) /algorithm, and the Chou-Talalay's Combination Index eq (CIE) /algorithm), are all based of the mass-action law (MAL) derivations. MAL is the only assumption, and the only "Model" (No Empirical formula, nor "Statistical "Model") 2.MEE are CIE are products of sequential derivations. CI calculation always requires MEE/algorithm, 3. The definitions of synergy (CI1), is finale (based on MAL), and 4.CI quantitatively/ universally determines/digitalize of the degree synergism or the antagonism, but it does not say how and why synergy or antagonism occurred. Mechanism is a separate study, which is frequently complex, time consuming, and costly, especially in vivo. Attached is a Chou, EB-2021 ASPET abstract for information and illustration.
My website, www.Combosyn.com, for the mass-action law unified general pharmacodynamics theory for single drug dynamic parameters, Dm and m, (MAL-PD) and its combination index (CI) theorem that quantitative determination/simulation of Synergism (CI1), have been updated on November 23, 2021.
To date, the MAL-PD/CI has been cited over15,000 times in over 1,420 scientific journals internationally, encompassing broad spectrum of biomedical sciences.
This website has updated references, provided registration for free-download of CompuSyn software, instruction for data entries, video demos, theory and applications in 74 illustrative PDF slides (please see attached below), and examples of specific data analysis and the full computer print-outs and data/results digital/indexed interpretations.
Thank you for your interest in the MAL-PD and CI.
T.C. Chou
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