GCN2iB is an ATP-competitive inhibitor of serine/threonine protein kinase, stress-responsive kinase (GCN2), with IC50 of 2.4 nM.

GCN2:2.4 nM

METHODS: HEK293 cells were treated with 4 nM to 4 μM Gcn2iB for 6 h in the presence or absence of Halofuginone (HF) treatment to explore the concentration-dependent effect of Gcn2iB on ISR activation.
RESULTS HF treatment resulted in increased levels of p-Gcn2, p-eIF2α, and Atf4, each of which decreased with increasing concentrations of Gcn2iB; p-Gcn2 induction decreased at 62.5 nM Gcn2iB or higher, and Atf4 induction decreased at 250 nM Gcn2iB; cells treated with Gcn2iB in the absence of HF exhibited a biphasic response to the induction of p-Gcn2, p-eIF2α, and Atf4, with increases in all three ISR markers observed in the range of 10 to 100 nM Gcn2iB; above 250 nM Gcn2iB, p-Gcn2 levels decreased to below those determined with vehicle, and Atf4 levels were not significantly induced; although Gcn2iB could inhibit Gcn2 stimulation by HF treatment, lower concentrations of Gcn2iB activated Gcn2 and the ISR in the absence of external stress. [1]

METHODS: HFD plus STZ-induced diabetic C57BL/6J mice were treated with intraperitoneal injection of GCN2iB (3 mg/kg) every other day for 6 weeks. At the end of the experiment, the mice were subjected to echocardiography.
RESULTS After GCN2iB treatment, the fasting blood glucose level (11.18 ± 1.44 vs. 17.42 ± 2.57 mmol/L) and body weight (28.94 ± 2.05 vs. 32.54 ± 1.49 g) of type 2 diabetic mice were significantly reduced; GCN2iB treatment had no effect on heart weight. Significant effects, but increased heart weight to body weight ratio; GCN2iB treatment significantly improved cardiac systolic function and increased left ventricular (LV) ejection fraction (EF). [2]