on-target effect
An on-target effect is anything a drug causes by doing exactly the job it was designed to do — acting on its intended target. If a drug is meant to block a particular enzyme, then every consequence that flows from blocking that enzyme is on-target, whether that consequence is the wanted cure or an unwanted side effect.
This is a subtle but vital idea: on-target does not mean 'good'. A drug can produce harmful effects precisely because it is hitting the right target very well. If the same target also does useful work elsewhere in the body, fully engaging it everywhere can cause predictable, mechanism-based side effects. These on-target toxicities cannot be designed away by making the molecule more selective, because the molecule is already on the protein it was aimed at — the only escape is a different target, restricted dosing, or local delivery.
Distinguishing on-target from off-target effects is one of the most useful diagnostic questions in drug development. If a side effect is on-target, it tends to track with potency and occupancy and to appear across all chemically distinct drugs against that target, hinting that the target itself, not the chemistry, carries the risk. That distinction guides whether to optimize the molecule, reconsider the target, or accept a manageable trade-off.
The dry cough caused by ACE inhibitors is on-target: it stems from the same enzyme blockade that lowers blood pressure (raising bradykinin levels), so it appears across the whole drug class rather than with one particular molecule.
On-target effects come from hitting the intended target — for better or worse.