Girolline

Girolline is a protein synthesis inhibitor and a functional modulator of eIF5A. Girolline induces ribosome stalling by interfering with the binding of eIF5A to ribosomes. Girolline also inhibits the production of IL-6 and IL-8, and induces cell cycle arrest in tumor cells. Girolline is applicable to research related to inflammatory diseases, solid tumors, leukemia and malaria^[1][2][3][4]. In Vitro:Girolline (0.08-40000 ng/mL; 4.5 h) inhibits flagellin-induced TLR5 NF-κB luciferase reporter gene activity in CHO-K1-TLR5 cells^[1].
Girolline (2 μg/mL; 7 h) potently inhibits flagellin-induced IL-8 secretion and NF-κB/AP-1 activity in THP1-derived macrophages^[1].
Girolline (2 μg/mL; 7 h) blocks flagellin-induced secretion of IL-6 and IL-8 in human peripheral blood mononuclear cells (PBMCs)^[1].
Girolline (8-5000 ng/mL; 7 h) dose-dependently inhibits NF-κB/AP-1 activity induced by various TLRs, IL-1β and TNF-α in HEK293 reporter cells, with significant inhibition observed at concentrations ≥200 ng/mL^[1].
Girolline (50 μM; 24 h) induces G₂/M cell cycle arrest in FL, HeLa and A549 tumor cell lines, with the most pronounced effect observed in FL cells^[2].
Girolline (5-50 μM; 24 h) induces concentration-dependent accumulation of polyubiquitinated p53 in FL cells^[2].
Girolline (0.1-1.0 μM; 1-4 days) induces dose- and time-dependent G2 phase arrest in human 293 cells, with the most prominent accumulation of G2/M phase cells observed at 1.0 μM for 48 h, while prolonged treatment leads to increased apoptotic cell death^[3].
Girolline (10-300 μM; 1 h) dose-dependently inhibits the interaction between hypusinated eIF5A and ribosomes in HEK293T cells^[4].
Girolline (1-5 μM; 16 h) selectively inhibits the translation of sequences containing AAA-encoded Lys (but not AAG-encoded Lys) in HEK293T cells, with longer AAA sequences correlating with stronger inhibitory effects^[4]. In Vivo:Girolline exhibits low toxicity in dogs and mice in preclinical toxicological studies^[2].