laczlacylaci

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I see that IC50 comes up a lot in passages, just wanted to confirm my understanding of the definition.
IC50=concentration of inhibitors needed to inhibit 50% of the reaction.

A high IC 50 would mean the inhibitor could be weak or a lot of substrate...
A low IC50 would mean strong inhibitor or less substrate?
 

theonlytycrane

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Yeah this is a good one to clarify. Think about it in terms of the inhibitor effectiveness. Let's say we have inhibitor A and inhibitor B.

A: 10mM to reach IC50

B: 1M to reach IC50

Which likely has more affinity for the enzyme its inhibiting? (This could be asked in terms of which has the lower Km).
 

aldol16

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IC50 will be important for pharmacokinetics, which is an essential part of any clinical trial (in the earlier stages). IC50 is the inhibitor concentration required to halve the response.
 

akimhaneul

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Yeah this is a good one to clarify. Think about it in terms of the inhibitor effectiveness. Let's say we have inhibitor A and inhibitor B.

A: 10mM to reach IC50

B: 1M to reach IC50

Which likely has more affinity for the enzyme its inhibiting? (This could be asked in terms of which has the lower Km).
I'm guessing it's A?
 

NextStepTutor_2

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Hi @laczlacylaci ! Let’s see how this might be plotted and how the AAMC could get creative with it.


The green dots show measurements made with controls. The left green dots have no inhibitor (i.e. 100%). Green dots on the right have maximum concentration of a standard inhibitor (i.e. 0%). The red dots are the results of an experimental dose-response curve, and span from one control to the other.

IC50 is the concentration of an inhibitor where the response (binding) is reduced to half it original value (i.e. no inhibitor present). Straightforward, right? However when researchers actually go to fit data to determine these values (we did a few exercises like this during MS II), there are some wrinkles the AAMC could bring up in a passage.


One value cannot summarize this curve. We would need two values, one to quantify the middle of the curve (drug potency) and one to quantify how low it gets (drug effect).

Relative IC50 is by far the most common definition, and the adjective relative is usually omitted. It is the concentration required to bring the curve down to point half way between the top and bottom plateaus of the curve. The right green dots are totally ignored with this definition of IC50. The AAMC could also bring this concept up when presenting a passage on agonist and antagonist interactions. With sufficient information provided about the concentrations of interacting ligands, estimated Kd values can be derived from the IC50 value defined this way.

Absolute IC50 is the concentration that provokes a response halfway between the left green dots and the right green dots. The horizontal gray lines show how 100% and 0% are defined, which then defines 50%. This term is not entirely standard. Since this value does not quantify the potency of a drug, it is not as accurate a representation of the drug ability (a good Q the AAMC could ask). This is unlikely to ever appear on the MCAT but you will see it in medical school.

Tl, dr

This is a concept you still study extensively in medical school, but do not go overboard on it for the MCAT. The Qs on this topic the AAMC has given only require a basic knowledge of enzyme kinetics and inhibition. Think of IC50 like Km. A low Km indicates a highly efficient enzyme binding activity, while a low IC50 says the same about the inhibitor.

Hope this helps, good luck!
 
OP
laczlacylaci

laczlacylaci

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Jun 20, 2016
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Hi @laczlacylaci ! Let’s see how this might be plotted and how the AAMC could get creative with it.


The green dots show measurements made with controls. The left green dots have no inhibitor (i.e. 100%). Green dots on the right have maximum concentration of a standard inhibitor (i.e. 0%). The red dots are the results of an experimental dose-response curve, and span from one control to the other.

IC50 is the concentration of an inhibitor where the response (binding) is reduced to half it original value (i.e. no inhibitor present). Straightforward, right? However when researchers actually go to fit data to determine these values (we did a few exercises like this during MS II), there are some wrinkles the AAMC could bring up in a passage.


One value cannot summarize this curve. We would need two values, one to quantify the middle of the curve (drug potency) and one to quantify how low it gets (drug effect).

Relative IC50 is by far the most common definition, and the adjective relative is usually omitted. It is the concentration required to bring the curve down to point half way between the top and bottom plateaus of the curve. The right green dots are totally ignored with this definition of IC50. The AAMC could also bring this concept up when presenting a passage on agonist and antagonist interactions. With sufficient information provided about the concentrations of interacting ligands, estimated Kd values can be derived from the IC50 value defined this way.

Absolute IC50 is the concentration that provokes a response halfway between the left green dots and the right green dots. The horizontal gray lines show how 100% and 0% are defined, which then defines 50%. This term is not entirely standard. Since this value does not quantify the potency of a drug, it is not as accurate a representation of the drug ability (a good Q the AAMC could ask). This is unlikely to ever appear on the MCAT but you will see it in medical school.

Tl, dr

This is a concept you still study extensively in medical school, but do not go overboard on it for the MCAT. The Qs on this topic the AAMC has given only require a basic knowledge of enzyme kinetics and inhibition. Think of IC50 like Km. A low Km indicates a highly efficient enzyme binding activity, while a low IC50 says the same about the inhibitor.

Hope this helps, good luck!

This is awesome, thank you! I liked the comparison with Km