It’s “well known” that we all need to find the stronger inhibitors against any specific therapeutic target as possible. The motivation is that the strongest inhibitors are most probably less toxic. It’s so obvious and thus needs to be checked.

To do so we took drug cards from the DrugBank and attempted to correlate the activity against the specific therapeutic targets (in log units) with LD50 (in log units as well).

The results are impressive on its own. In any activity range the toxicity of the compounds is very uniform. Let me repeat: there is the same probability to hit a highly toxic compound in pKI range, say 8-10 and 6-8. Once again: the toxicity is the ability of a compound to interact with a number of allimportant targets and has nothing to do with the ability of a compound to bind to a specific target of a therapeutic interest. What matters is of course the so called therapeutic window, which is the ratio of activity vs. toxicity.

So what’s the answer? Yes, we do need those nM-molecules. The toxicity of a compound does not depend on the efficacy against a specific target. On the other hand, the more is the efficacy, the larger is the therapeutic window (thanks to E. Getmantsev!).

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