BI03782253

BI03782253 is a preclinical small-molecule dual inhibitor of glutaminyl-peptide cyclotransferase (QPCT) and glutaminyl-peptide cyclotransferase-like protein (QPCTL), collectively referred to as QPCT/L [1]. Developed by Boehringer Ingelheim, the compound is being investigated for its therapeutic potential in pulmonary fibrosis [1]. QPCT/L enzymes catalyze the conversion of N-terminal glutamine or glutamate residues into cyclic pyroglutamate, a post-translational modification that stabilizes proteins such as CD47 and various chemokines. While BI03782253 demonstrated potent anti-fibrotic activity in a bleomycin-induced pulmonary fibrosis model, in vivo dose escalation was found to trigger inflammatory responses driven by interferon-gamma (IFN-γ) and CD8+ T-cells, suggesting potential safety risks at high concentrations [1].