GCN2-IN-6 经酶法和细胞分析证实，是一种口服有效GCN2抑制剂，IC50分别为1.8 nM和9.3 nM。GCN2-IN-6 还是 eIF2α 激酶PERK抑制剂，在酶法测定和细胞测定中的IC50分别为 0.26 nM 和 230 nM。

GCN2-IN-6 is a potent and orally available GCN2 inhibitor confirmed by in-house enzymatic (IC50: 1.8 nM) and cellular assays (IC50: 9.3 nM). GCN2-IN-6 is also an eIF2α kinase PERK inhibitor with IC50s of 0.26 nM in enzymatic assay and 230 nM in cells respectively.

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. 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 asparagine depleting agent asparaginase.?Treatment with GCN2-IN-6 greatly sensitizes CCRF-CEM cells to asparaginase.

GCN2-IN-6 ( 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.

2183470-09-7

C19H12Cl2F2N4O3S

485.29

DMSO:250 mg/mL (515.16 mM),Need ultrasonic
Powder: -20°C for 3 years
In solvent: -80°C for 2 years