Someone says that candidate drugs should have a small value of IC50 in cytotoxicity assay to be proposed as a "candidate drug" or "promising drug". However, others say that the most important point is selectivity against cancer cells instead of healthy cells.
Could you share your opinions? I am open to articles that you'd suggest..
Having a relatively low IC50 versus cancer cells is valuable because it helps keep the dose required for in vivo efficacy low. This can help minimize off-target systemic toxicity of the drug, and make it easier to achieve the necessary blood levels of the drug.
It is also important for minimizing toxicity of the drug that it should be relatively non-toxic to normal cells, so it is important to have selectivity, too.
If you had a drug that was essentially non-toxic to normal cells, lacked off-target toxicity, and achieved high blood levels, you could get away with the drug having a relatively high IC50 against the cancer cells.
It's all relative, but there tend to be guidelines in drug discovery projects, based on experience, as to what sort of IC50 and selectivity are likely to be needed.
Hi Adem Özleyen,
Adam B Shapiro has nicely explained to your query.
A drug with low IC50 or high potency is useful as you can administer lower clinical doses to patients, minimizing off-target toxicity (thus beneficial to patients), and may be a better option in comparison if a competitive drug is already present in market which is less potent than your drug (thus bringing more money).
Selectivity is also important, not only in comparison to healthy cells, but also various isoforms of the target where you want to hit/block preferably.
The ultimate aim is to design a better drug benefitting the patient. There are no guidelines from any agencies for this..it all depends on the experience and scientific judgement.
Please find attached relevant literature.
Dear Adam B Shapiro and Varun Ahuja ,
Thanks for sharing your approaches..
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