GCN2-IN-7

Research use only, not for human use.

GCN2-IN-7 is an orally active, potent and selective inhibitor of the environmental sensing protein GCN2 with anti-tumor activity and can be used to study melanoma.

GCN2-IN-7 (compound 39) is an orally active and selective general control nonderepressible 2 (GCN2) inhibitor (IC50=5 nM). GCN2-IN-7 shows anti-tumor activity in vivo.

GCN2-IN-7 (600 nM; 3 d) alleviates myeloid-derived suppressive cells (MDSC)-related T cell suppression and restores T cell proliferation.:Cell Proliferation Assay Cell Line:CD8+ T cells from WT and GCN2KO cells Concentration:600 nM Incubation Time:3 days Result:Relieved MDSC suppression of proliferation of the co-cultured CD8+ T cells with significant relief at 600 nM.

GCN2-IN-7 (oral gavage; 15 mg/kg; BID; 17 d) shows robust target engagement in vivo at a reasonable dose.GCN2-IN-7 (oral gavage; 50 mg/kg; BID; 17 d) inhibits tumor growth in vivo of the LL2 syngeneic mouse tumor model.Animal Model:Balb/c mice injected with RENCA cells Dosage:15 mg/kg Administration:Oral gavage; 15 mg/kg; BID; 17 daysResult:Showed robust target engagement of GCN2 in both tumor (average of 84%) and spleen (average of 80%) tissues.Showed an average of 65% reduction of downstream marker Activation Transcription Factor 4 (ATF4) in compound-treated mice compared to the vehicle treatment group.Animal Model:LL2 syngeneic mouse model Dosage:50 mg/kg Administration:Oral gavage; 50 mg/kg; BID; 17 days Result:Showed tumor growth inhibition (56%) after 26 days of dosing compared to the vehicle group.

——

Apoptosis

PERK

PERK

——

——

2396465-33-9

527.44

C22H23BrN8OS

>98% (HPLC)

In Vitro:?DMSO : 50 mg/mL (94.80 mM; Ultrasonic )

BrC=1C=2C(N(N1)C3=CC=C(C=C3)C4=NN=C(C)S4)=NC(N[C@H]5C[C@@](C(NC)=O)(C)CC5)=NC2

——

(-20℃)

With Ice Pack

≥ 2 years