GCN2-IN-1 (A-92) (Synonyms: A-92, GCN2 Inhibitor 1, General Control Nonderepressible 2 Kinase Inhibitor 1) |
Catalog No.GC32771
One-Click Copy Product Info
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GCN2-IN-1 (A-92) is a potent and selective inhibitor of General Control Nonderepressible 2 kinase (GCN2).
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1448693-69-3
Sample solution is provided at 25 µL, 10mM.
GCN2-IN-1 (A-92) is a potent and selective inhibitor of General Control Nonderepressible 2 kinase (GCN2)[1]. By inhibiting the activity of GCN2 kinase, GCN2-IN-1 affects the phosphorylation of its downstream eukaryotic translation initiation factor eIF2α, thereby modulating the Integrated Stress Response (ISR) signaling pathway[2]. GCN2-IN-1 shows potential as a chemotherapeutic agent for cancer treatment, with mechanisms of action related to the regulation of the cell cycle and stress responses[3-4].
In vitro, treatment of APC-deficient colorectal cancer cells (SW480) with GCN2-IN-1 (3μM) for 6 hours significantly reduced the phosphorylation level of eukaryotic translation initiation factor 2α (eIF2α) and induced apoptosis[5]. Pre-treatment of U2OS cells with GCN2-IN-1 (4μM) for 3 hours, followed by transfection with in vitro transcribed mRNA (1μg) for 1.5 hours, significantly inhibited the formation of stress granules (SGs) induced by mRNA transfection[6]. Treatment of HeLa cells with GCN2-IN-1 (0.63-5μM) for 5 hours significantly inhibited the activity of its target GCN2 and reduced basal eIF2α phosphorylation levels, while increasing protein synthesis[7]. Pre-treatment of U2OS cells with GCN2-IN-1 (4μM) for 3 hours, followed by stimulation with VRB (75μM) for 1 hour, significantly enhanced the formation of stress granules (SGs) and altered granule dynamics[8].
References:
[1] Chen C, Xie Y, Qian S, et al. Multifaceted role of GCN2 in tumor adaptation and therapeutic targeting. Transl Oncol. 2024 Nov;49:102096.
[2] Ghosh JC, Perego M, Agarwal E, et al. Ghost mitochondria drive metastasis through adaptive GCN2/Akt therapeutic vulnerability. Proc Natl Acad Sci U S A. 2022 Feb 22;119(8):e2115624119.
[3] Skrott Z, Mistrik M, Andersen KK, et al. Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4. Nature. 2017 Dec 14;552(7684):194-199.
[4] Gold LT, Masson GR. GCN2: roles in tumour development and progression. Biochem Soc Trans. 2022 Apr 29;50(2):737-745.
[5] Angel M, Fleshler E, Atrash MK, et al. Nuclear RNA-related processes modulate the assembly of cytoplasmic RNA granules. Nucleic Acids Res. 2024 May 22;52(9):5356-5375.
[6] Szaruga M, Janssen DA, de Miguel C, et al. Activation of the integrated stress response by inhibitors of its kinases. Nat Commun. 2023 Sep 8;14(1):5535.
[7] Schmidt S, Gay D, Uthe FW, et al. A MYC-GCN2-eIF2α negative feedback loop limits protein synthesis to prevent MYC-dependent apoptosis in colorectal cancer. Nat Cell Biol. 2019 Nov;21(11):1413-1424.
[8] Schwed-Gross A, Hamiel H, Faber GP, et al. Glucocorticoids enhance chemotherapy-driven stress granule assembly and impair granule dynamics, leading to cell death. J Cell Sci. 2022 Jul 15;135(14):jcs259629.
| Cell experiment [1]: | |
Cell lines | U2OS cells (human osteosarcoma cell line) |
Preparation Method | U2OS cells were maintained in low-glucose Dulbecco's modified Eagle medium (DMEM) supplemented with 10% fetal bovine serum (FBS). U2OS cells were treated with GCN2-IN-1 (4μM) for 3 hours prior to transfection with in vitro transcribed mRNA. |
Reaction Conditions | 4µM; 3h pre-treatment |
Applications | GCN2-IN-1 reduced basal eIF2α phosphorylation levels. This inhibition resulted in a significant decrease in stress granule (SG) formation induced by mRNA transfection, highlighting the essential role of GCN2-mediated eIF2α phosphorylation in SG assembly under conditions of cytoplasmic mRNA abundance. |
References: | |
| Cas No. | 1448693-69-3 | SDF | |
| Synonyms | A-92, GCN2 Inhibitor 1, General Control Nonderepressible 2 Kinase Inhibitor 1 | ||
| Canonical SMILES | C1(NC2=CN(C3CCOCC3)N=C2)=NC=C(N=NN4C5=CC6=C(C=C5)C=NN6)C4=N1 | ||
| Formula | C19H18N10O | M.Wt | 402.41 |
| Solubility | DMSO : 60 mg/mL (149.10 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.485 mL | 12.4251 mL | 24.8503 mL |
| 5 mM | 497 μL | 2.485 mL | 4.9701 mL |
| 10 mM | 248.5 μL | 1.2425 mL | 2.485 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)