GCN2-IN-6 (Compound 6d) 是一种有效的口服 GCN2 抑制剂，通过酶法 (IC₅₀ 为 1.8 nM) 和细胞分析 (IC₅₀ 为 9.3 nM) 证实。GCN2-IN-6 还是 eIF2α 激酶 PERK 抑制剂，IC₅₀ 为 0.26 nM (酶法测定) 和 230 nM (细胞测定)。

GCN2-IN-6 (Compound 6d) is a potent, and orally available GCN2 inhibitor confirmed by in-house enzymatic (IC 50 of 1.8 nM) and cellular assays (IC 50 of 9.3 nM). GCN2-IN-6 is also a eIF2α kinase PERK inhibitor with an IC 50 of 0.26 nM (in enzymatic assay) and 230 nM (in cells).

Solid

IC50: 1.8 nM (GCN2, in-house enzymatic) and 9.3 nM (GCN2, cellular assays); 0.26 nM (PERK, in-house enzymatic) and 230 nM (PERK, cellular assays)

To examine the impact of GCN2 inhibition on cancer cell proliferation, acute lymphoblastic leukemia (ALL) CCRFCEM cells are treated with GCN2-IN-6 (Compound 6d) in the presence of asparaginedepleting agent asparaginase. Treatment with GCN2-IN-6 greatly sensitizes CCRF-CEM cells to asparaginase. The moderate antiproliferative effects achieved by combining asparaginase and GCN2-IN-6 treatment are observed in GCN2-wildtype (WT) mouse embryonic fibroblast (MEF) cells but not in GCN2-knockout (KO) MEF. GCN2-IN-6 demonstrates suppression on p-GCN2, p-eIF2α, and ATF4 activated by asparaginase. has not independently confirmed the accuracy of these methods. They are for reference only.

GCN2-IN-6 (Compound 6d; 0.3-3 mg/kg; oral administration; for 8 hours; mice) treatment at 3 mg/kg suppresses both self-phosphorylation of GCN2 and the downstream effector ATF4 to the basal level following pretreatment with asparaginase. has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；4°C 2 years

[1]. Fujimoto J, et al. Identification of Novel, Potent, and Orally Available GCN2 Inhibitors with Type I Half Binding Mode. ACS Med Chem Lett. 2019 Sep 19;10(10):1498-1503.

In Vitro: DMSO : 250 mg/mL (515.16 mM; Need ultrasonic)配制储备液