How does one change a compound of drugs designed to be able to design new compounds to be better than our earlier designed of proteins binding? In other words, what are the criteria that must be considered?
You have to define "better". If you are taling about an in vitro interaction then you would want a higher affinity (lower Kd), if you are working with an in vitro enzyme assay then you want lower Ki which will often correlate with lower Kd. By want, what I really mean is that in these in vitro systems, a lower Kd/Ki is the only criteria you can use to determine if one drug is "better" than another. However if you are working in living cells or animals then a lower Ki/Kd won't alway correlate with increased efficacy. In the former situtation, altering the drug should only alter the binding affinity (though not always in enzyme assays, especially if you are working with a non- or uncompetitive inhibitor). In the latter case altering the drug can alter: the interaction with the target; interactions with secondary targets; transport into and out of the cell; metabolism; and distribution. I think in your case you are talking about an in vitro assay with purified enzyme, but be aware that decreasing Kd won't always make for a more efficacious drug, just look at the Vioxx debacle.
- Badges
- Science topic
- Similar topics
- Chemistry
- Pharmacology