High-throughput drug screening relies on low-cost primary assays to prioritize compounds for more expensive dose-response profiling, where potency is ultimately quantified.
Current screening strategies largely focus on identifying compounds that will confirm biological activity on follow-up, implicitly assuming that confirmed activity will also yield a usable potency estimate.
However, confirmed biological activity in screening does not necessarily translate into a quantifiable potency, because active compounds can still fail to produce a reportable dose-response estimate.
We therefore present a framework for modeling quantifiability, whether follow-up testing will yield a usable potency estimate, as a distinct triage objective from biological activity.
Quantifiability was strongly predictable from the preceding low-cost screen, with most predictive information arising from the observed screening features rather than molecular structure.
Response-based predictors remained robust on previously unseen chemical scaffolds and generalized across held-out assay-mechanism families, while the probability of successful quantification varied strongly with response amplitude and assay context.
These findings establish experimental measurability, distinct from biological activity, as a predictable property of screening outcomes and show that quantifiability-aware triage can improve the allocation of costly dose-response profiling capacity.