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I am interested in knowing how to find/optimise the concentration needed for a drug effect in cell. and different organism

For example, if I use 1 micro molar for treating a cell. Should I use 10 nM when I use C.elegant ? how do you define or tune such a concentration ? Please give me reference too if there is any

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Typically when working with compounds I come from two directions:

Does the drug appear in the literature and what concentration do they use?

I think a quick literature search is a wonderful thing because like many problems, often times someone else has asked your question (what's the right concentration?), and done the necessary legwork to find you a starting point. I don't think we can avoid this next part though, especially if your drug has never been used in your system/organism/etc.

Titrate your compound

For almost anything out there, even if the manufacturer has a number in mind you should always titrate for your own application. Things aren't simply going to work for you as they did for another investigator, in part, because you're never asking the same question as another investigator. A good literature search can help strengthen your finding, however.

In finding the working concentration for your compound you aren't going to be doing the optimizing. It doesn't make sense to find the best concentration when you don't know what concentration works to begin with. As a rule of thumb I try to make the range of titers broad enough that I can see where undesirable or no-effect is, so for example with a drug I'd try 100µM, 10µM, 1µM, 100nm, 10nM, 1nM, 0.1nM.

If you can pick out a good working concentration there, you can optimize by using a tighter criteria. For example, I find that 10nM works the best; now I know 100nM and 1nM are my respective maximum and minimum. May I'd try 40nM, 20nM, 10nM, 5nM, 2.5nM.

It's important to reduce technical variability by using the same starting materials such as cell number for each condition to get the best titer.

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  • $\begingroup$ thank you so much for your message. This is definitely good. however, my main question is that is it normal that a drug with nano mollar works in a cell while with a 100 fold more work in e.g. C.elegant? or any other animal model? how can I justify that? do you have such an example? for example when i use more than nano molar the drug will kill the cell imagine what will happen if I use micro molar . is this ajustable ? do you know of any paper with different concentration in cell and animal model? $\endgroup$ – Nik May 15 '17 at 21:17
  • $\begingroup$ I have no way of knowing without the identity of the drug. $\endgroup$ – CKM May 15 '17 at 21:43
  • $\begingroup$ for instance Rapamycin $\endgroup$ – Nik May 15 '17 at 22:32
  • $\begingroup$ So rapamycin as an example: I'd probably find my usage close to 10-20nm in cell culture, which I think is standard. However, I can find two references, immediately, that use rapamycin at 200µM and 100µM, respectively (ref1, ref2). Reference 1 makes an important point: higher concentrations are needed for C. elegans due to bioavailability. $\endgroup$ – CKM May 16 '17 at 0:35
  • $\begingroup$ Important to note is that different species have different kinetics to their usage of the same drug. $\endgroup$ – CKM May 16 '17 at 0:38

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