By Marc Navare, Ph.D.
What is pIC50? Simply stated, pIC50 is the negative log of the IC50 value when converted to molar.
For example, an IC50 of 1 uM is 1 x10^-6 M and that’s equal to a pIC50 of 6.
An IC50 of a nanomolar compound is 1 x10^-9 M, which is a pIC50 of 9.
Using the pIC50 encourages the logarithmic thinking that is required for dealing with concentration-dependent relationships.
But, why would you stop using IC50 values if this is what you have always done?
Why make the switch?
Because the nature of potency values is logarithmic, how you then report your data should therefore also be log based.
If you look at dose-response curves, they are sigmoidal when you plot them in logarithmic space.
Using pIC50 is the proper way to think about the data.
If your potency goes down because you’ve gone from micromolar to nanomolar, that’s an exponential change, not a linear change.
pIC50 is really the right way to think about potency of compounds, which is why people have been using logarithmic scale for compound concentration for ages.
3 Analogies To Help You Think Logarithmically And Improve Your Understanding of pIC50
But, when switching to the pIC50, there is definitely a transition time.
It’s like going from the imperial measurement system to the metric measurement system.
It’s a little painful at first, but it’s worth doing.
Eventually, pIC50 will become intuitive because it’s actually very natural for humans to think that bigger numbers are better.
To help make the transition easier, it’s helpful to think of other common logarithmic situations you have already encountered so you can encourage the adoption of logarithmic thinking.
Here are 3 logarithmic situations to help you improve your understanding of pIC50…
1. The Richter scale
If you have ever lived in earthquake country, you’re probably familiar with the Richter scale.
The Richter scale is a logarithmic method of reporting the amplitude of an earthquake, which means a 10-fold increase in shaking is a 1-fold increase in the Richter scale.
Thinking about pIC50 as the Richter scale for drug discovery can be helpful because the numbers that are significant in terms of an earthquake are also significant in terms of the potency of compounds.
For people who are trying to make the adjustment from IC50 to pIC50, it can be a little awkward at first.
For example, the Richter scale earthquake of 3.0 is not felt by many people.
There’s no damage.
Likewise, it’s not much to write home about in terms of pIC50.
A pIC50 of 3.0 is a millimolar compound.
At 6.0, things start to get a little more interesting.
With a 6.0 earthquake, you will start to get some moderate damage to populated areas and a 6.0 pIC50 will start to get your chemists excited because now you’re getting to a micromolar compound.
As you go higher, you’re getting nicer and nicer potency — or a more and more damaging earthquake.
Once you reach 9.0, that is not an earthquake you want to be around for. That’s epic destruction.
But, a pIC50 of 9.0 — that’s the kind of potency you want to see in the inhibitors you get from your chemists.
2. The pH scale
Thinking logarithmically is not as foreign as it might seem.
It’s actually something you’ve been doing for years, ever since you were knocking over graduated cylinders in high school.
Ever since you first encountered the pH scale.
Because pH is the negative log of the hydronium ion concentration in molar.
When thinking about pH, you don’t think about hydronium ion concentrations in micromolar or millimolar levels.
You’re used to this. You think of them simply as pH.
You’ve been thinking logarithmically all along.
You can use logarithmic thinking not just for pH, but also for IC50 or potency data by using pIC50. The pIC50 is just the negative log of the IC50in molar.
3. Potency of Household Cleaners.
Logarithmic thinking can even start at home.
Just think about your kitchen or bathroom cleaners.
The label probably says something like, “kills 99.9% of viruses and bacteria”.
Well, what does that mean?
Does it mean that if I bought a different cleaner that kills 99.99% instead of 99.9%, it would only really be .09% better?
Or, to capture the concept even more obviously, if an antibacterial kills 99.9%, can I put it on twice to kill 199.8%?
While these are both facetious and silly questions, they both belie the fact that there is a fallacy of thinking about exponential data in an arithmetic universe.
In anti-infective circles, a 99.9% killing is actually referred to as a three log kill.
Why is that?
If something kills 90% of the infectious organisms, that means it’s a 10-fold reduction in the infectious organism count, and that is often referred to as a one log kill or one order of magnitude.
99% killing is a 100-fold reduction, and 99.9% killing is a 1,000-fold reduction — you get the gist.
Recognizing the ridiculous nature of thinking about this common logarithmic measurement within an arithmetic setting will help you realize and understand the fallacy of using non-logarithmic equations when discussing potency values.