ontargettoksisuus

On-target toxicity refers to adverse effects that occur when a drug or therapeutic agent binds to its intended molecular target but at an unintended site or time, or with an exaggerated biological response. This differs from off-target toxicity, where the agent interacts with molecules other than its intended target, leading to side effects. In on-target toxicity, the drug is working as designed, but the consequences of its action are undesirable.

This phenomenon can arise for several reasons. For instance, the intended target molecule might be present in tissues or cells where its activation is not beneficial, or even harmful, in the context of the disease being treated. Alternatively, the drug might be too potent, leading to an overactivation of the target pathway, or it might remain active for too long, causing prolonged effects. Genetic variations in patients can also contribute, leading to an exaggerated response to even normal levels of target engagement.

Understanding on-target toxicity is crucial for drug development and patient care. It requires careful consideration of the target's role in different physiological processes and the potential for unintended consequences. Strategies to mitigate on-target toxicity can include dose optimization, careful patient selection, or developing prodrugs that are activated only at the desired site. It highlights the complexity of translating a drug's mechanism of action into a safe and effective therapy.