Fig. 5: Real-world applicability in flagging DILI risk in recent clinical failures.
From: A large-scale human toxicogenomics resource for drug-induced liver injury prediction
A. ToxPredictor provides outputs including the first DILI concentration, safety margin, and corresponding risk classification. Clinical validation confirms that drugs labeled as high risk by the model, such as TAK-875, Evobrutinib, and BMS-986142, were recently withdrawn and halted in Phase III trials due to DILI. Conversely, low-risk drugs such as Tofacitinib and Upadacitinib, as classified by the model, exhibit no DILI association. B Model-derived DILI risk likelihood curves for representative compounds are plotted against hypothetical Cmax values. These curves delineate dose regimes associated with low, medium, mid-high and high DILI risk, enabling dose recommendations within the low-risk range. Risk classification is determined based on the actual efficacious Cmax of each compound: Evobrutinib is classified as high risk, Rilzabrutinib as medium risk (recommended dose <100 mg q.d.), and Remibrutinib as low risk (recommended dose <155 mg q.d.). This demonstrates the model’s utility in guiding dose selection to minimize DILI risk.
