Comment by entee

There's a lot that can be learned with building-block based experiments. If you do a building block based experiment then train a model, then predict new compounds, the models do generalize meaningfully outside the original set of building blocks into other sets of building blocks (including variations on different ways of linking the building blocks). Granted that's not the "fully novel scaffold" test, however it suggests that there should be some positive predictive value on novel scaffolds.

We've done work in this area and will be publishing some results later in the year.