| Identification | Back Directory | [Name]
GCN2-IN-6 | [CAS]
2183470-09-7 | [Synonyms]
GCN2-IN-6
Eukaryotic Initiation Factor (eIF),GCN2 IN 6,GCN2IN6,Inhibitor,inhibit,GCN-2-IN-6
Benzenesulfonamide, N-[3-[2-(2-amino-5-pyrimidinyl)ethynyl]-2,4-difluorophenyl]-2,5-dichloro-3-(hydroxymethyl)- | [Molecular Formula]
C19H12Cl2F2N4O3S | [MOL File]
2183470-09-7.mol | [Molecular Weight]
485.29 |
| Chemical Properties | Back Directory | [Boiling point ]
719.2±70.0 °C(Predicted) | [density ]
1.70±0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
6.62±0.10(Predicted) | [color ]
Light yellow to yellow |
| Hazard Information | Back Directory | [Uses]
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]. GCN2-IN-6 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups. | [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.
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| [IC 50]
GCN2 | [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. DOI:10.1021/acsmedchemlett.9b00400 |
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