2183470-09-7

2183470-09-7 structure

Name: GCN2-IN-6
Chemical Name: GCN2-IN-6
CAS Number: 2183470-09-7
Molecular Formula: C₁₉H₁₂Cl₂F₂N₄O₃S
Molecular Weight: 485.29
Catalog: Research Areas Cancer
Create Date: 2019-12-07 12:45:38
Modify Date: 2024-01-02 11:52:04
GCN2-IN-6 (Compound 6d) is a potent, and orally available GCN2 inhibitor confirmed by in-house enzymatic (IC50 of 1.8 nM) and cellular assays (IC50 of 9.3 nM). GCN2-IN-6 is also a eIF2α kinase PERK inhibitor with an IC50 of 0.26 nM (in enzymatic assay) and 230 nM (in cells)[1].

Name	GCN2-IN-6

Description	GCN2-IN-6 (Compound 6d) is a potent, and orally available GCN2 inhibitor confirmed by in-house enzymatic (IC50 of 1.8 nM) and cellular assays (IC50 of 9.3 nM). GCN2-IN-6 is also a eIF2α kinase PERK inhibitor with an IC50 of 0.26 nM (in enzymatic assay) and 230 nM (in cells)[1].
Related Catalog	Research Areas >> Cancer
Target	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)[1]
In Vitro	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[1].
In Vivo	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[1]. Animal Model: Mice bearing CCRF-CEM cells xenografts[1] 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.
References	[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.

Molecular Formula	C₁₉H₁₂Cl₂F₂N₄O₃S
Molecular Weight	485.29

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