Researchers identified entrectinib as a potential drug repurposing candidate for inflammatory bowel disease after analyzing genetic regulation across 27 blood cell populations and 43 intestinal cell types, according to a peer-reviewed study published in Nature Communications. The research team paired expression quantitative trait locus (cis-eQTL) mapping with single-cell RNA sequencing data from the ileum, colon, and rectum alongside gene expression profiles from patients.
The investigators detected more than 95,000 cis-eQTL affecting over 13,000 e-genes in total. These genetic variants clustered into more than 24,000 regulatory modules across the examined cell types.
The analysis matched regulatory modules to 140 disease risk loci previously identified through genetic association studies. That matching process implicated more than 300 e-genes that had not previously been connected to inflammatory bowel disease. Among those candidates, 152 matching e-genes showed perturbed expression in the blood or gut tissues of patients.
The findings highlighted entrectinib as a specific repurposing candidate. The small molecule acts by binding NEK7 to inhibit the NLRP3 inflammasome, addressing targets where expression shifts from genetic variants align with observed disease processes.
Viacheslav A. Petrov and Yumie Tokunaga contributed equally to the work, which was led by researchers including Michel Georges and Souad Rahmouni at the University of Liège GIGA Institute. The manuscript was submitted on November 4, 2024, accepted on August 4, 2026, and published on September 1, 2026.
