GCN2iB (acetate)

GCN2iB acetate is an ATP-competitive, selective GCN2 inhibitor with an IC₅₀ of 2.4 nM. GCN2iB acetate inhibits the activation of the GCN2 pathway and upregulates GPX4. GCN2iB acetate enhances the anticancer effect of ASNase against acute lymphoblastic leukemia. GCN2iB acetate increases left ventricular ejection fraction, while reducing fasting blood glucose and myocardial fibrosis. GCN2iB acetate can be used in research related to acute lymphoblastic leukemia, acute myeloid leukemia and diabetic cardiomyopathy^[1][2]. In Vitro:GCN2iB (1 μmol/L) acetate potently inhibits recombinant GCN2 with an IC₅₀ of 2.4 nmol/L, and exhibits high kinase selectivity, showing only extremely low off-target inhibitory activity in a screening panel containing 468 kinases^[1].
GCN2iB (10^-9-10^-5 M; 72 h) acetate enhances the antiproliferative effect of ASNase in GCN2-WT MEF cells, but shows no such effect in GCN2-KO MEF cells, confirming its inhibitory activity targeting GCN2^[1].
GCN2iB (1 μmol/L; 72 h) acetate sensitizes CCRF-CEM, MV-4-11 and SU.86.86 cells to the antiproliferative effect induced by ASNase^[1]. In Vivo:GCN2iB (10 mg/kg; twice daily; for 7 consecutive days) acetate acts synergistically with 1,000 U/kg ASNase to potently inhibit the growth of CCRF-CEM acute lymphoblastic leukemia (ALL) xenografts in mice, with a statistically significant interaction (P = 0.0007)^[1].
GCN2iB (10 mg/kg; twice daily; 3 days per week; for 28 consecutive days) acetate acts synergistically with 1,000 U/kg ASNase to improve the survival rate of mice with disseminated MOLT-3 acute lymphoblastic leukemia (ALL)^[1].
GCN2iB (3 mg/kg; i.p.; once every other day; for 6 consecutive weeks) acetate improves cardiac systolic function in diabetic mice induced by high-fat diet combined with Streptozotocin (HY-13753), increases left ventricular ejection fraction by 34.7%, and simultaneously reduces fasting blood glucose, myocardial lipid accumulation, oxidative stress and fibrosis^[2].
GCN2iB (3 mg/kg; intraperitoneal injection; once every 2 days; for 6 consecutive weeks) acetate improves cardiac systolic function in db/db mice, increases left ventricular ejection fraction by 14.5%, while reducing fasting blood glucose, decreasing myocardial lipid accumulation and alleviating oxidative stress^[2].