To isolate effects due to macrocyclization from other structural differences that might affect the behavior of the compounds, we focus on examples that report the properties of a macrocycle together with an acyclic precursor with identical structure except for the chemical linkage that closes the macrocycle ring. For this reason, the macrocyclic/acyclic compound pairs we discuss below do not necessarily comprise the acyclic compound that was the true starting point for the project with the final macrocyclic drug or clinical candidate, but rather the acyclic/MC compound pair that provide the most direct insight as into the effects of macrocyclization.