what are the criteria for choosing enzyme inhibitors as a potential drug for therapeutic treatment of disease?

First, it has to inhibit the enzyme you want and not inhibit anything else. It also has to not cause any undesired effects by inhibiting the target enzyme. Sometimes the same enzyme is present in more than one tissue, so the same inhibitor can fix a problem in one organ and cause a problem somewhere else.

Next the drug needs to be soluble. As you digest a pill, receive a shot, or take an IV, the drug becomes diluted as it enters the bloodstream. If it isn't very soluble to begin with, it's nearly impossible to reach therapeutic concentrations in a patient.

The drug also must be able to reach it's target. If the target enzyme exists inside a cell, the drug must be able to enter the cell. Often a great inhibitor makes a lousy drug because it can get through the plasma membrane.

Finally the drug should ideally be left alone by the Cytochrome P450 enzymes of the liver. Many drugs are metabolized by P450, which is why this is a major source of drug interactions. Further, some of the P450 isotypes vary widely from person to person. This means that the safe dose for one person could be lethal in another, and at this point it's basically impossible to predict who those people are.

The bottom line is that the drug has to be bioavailable, safe and effective.

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