Apoptotic signatures allow early and rapid screening of drug-induced liver injury to accelerate drug discovery.

ABSTRACT:

Background

Early detection of drug-induced liver injury (DILI) during drug development is crucial for reducing drug attrition and ensuring the safety of patients. A versatile, biologically interpretable, and dose-dependent screening approach is therefore needed to inform early stop/go decisions and therapeutic margins.

Methods

We have developed AEGIS (Apoptotic Effector Genes In Safety), a preclinical DILI risk screening and prioritization tool that quantifies dose dependent perturbation of apoptosis-regulating transcription factors from transcriptomics data. We profiled transcriptomic responses after short exposures across primary human hepatocytes (PHH), HepG2/C3A cells, RAW 264.7 cells, and an acute Balb/c mouse study. From these profiles, AEGIS provides quantitative risk

SUBMITTER: Hellgren J 

PROVIDER: S-EPMC12827481 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature