Because they are computationally expensive, requiring at least several seconds for typical lead-like molecules, CASP is usually not used as part of the VS or DND in-the-loop scoring functions. Rather, they are used to post-process the most interesting molecules from these pipelines. Despite considerable progress in the recent years, and their usefulness as a filtering step to remove clearly problematic molecules, modern CASP tools still have limitations. The reaction models can fail, in particular for less well precedented reactions . It is not fully established whether condition and yield prediction works well enough already . Search algorithms can lead to strategically questionable routes in particular for more complex molecules . Organic chemistry expertise is still required to inspect the results.