One of the problems with excellent data in vitro is that it is not always guaranteed to be equivalent to data in vivo. Therefore, it is important that what gives in vitro problems are resolved before getting the drug into in vivo studies to give it a better chance.
For the following problems, how would you address each of the following for a target in the ER (CFTR= cystic fibrosis Transmembrane Conductance Regulator)?
1. If the drug is a small molecule with a carboxylic acid functional group with a pKA of 2.2.
2. If the drug is a base with a functional amine group with a pKA of 8.4.