GCN2-IN-6

Research use only, not for human use.

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 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.(In Vitro):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.(In Vivo):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.

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Animal Model:Mice bearing CCRF-CEM cells xenografts Dosage:0.3 mg/kg, 1 mg/kg, and 3 mg/kg Administration:Oral administration; for 8 hours Result:Suppressed both self-phosphorylation of GCN2 and the downstream effector ATF4 to the basal level following pretreatment with asparaginase.

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Others

Other Targets

nitric oxide

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2183470-09-7

485.29

C19H12Cl2F2N4O3S

>98% (HPLC)

In Vitro:?DMSO : 250 mg/mL (515.16 mM)

Nc1ncc(cn1)C#Cc1c(F)ccc(NS(=O)(=O)c2cc(Cl)cc(CO)c2Cl)c1F

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(-20℃)

With Ice Pack

≥ 2 years