In modern drug discovery, evaluating a compound's ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) profile is just as critical as ensuring its therapeutic efficacy. Historically, a primary reason drug candidates fail during costly, late-stage clinical trials is unexpected toxicity.

Mechanisms of Toxicity and Drug Properties Drug toxicity, including unpredictable idiosyncratic adverse drug reactions (IDRs), is frequently triggered when normal metabolic processes bioactivate a drug into highly reactive metabolites. These reactive species can covalently bind to cellular proteins or DNA, leading to severe organ damage or immune hypersensitivity. The specific molecular substructures or functional groups prone to this hazardous bioactivation are known as structural alerts or toxicophores.

Beyond specific toxicophores, g ...