GCLCi1
GCLCi1 is an orally active glutamate-cysteine ligase catalytic subunit (GCLC) inhibitor and ferroptosis inducer. GCLCi1 blocks the rate-limiting step of glutathione synthesis, leading to GSH depletion, elevated reactive oxygen species and lipid peroxidation. GCLCi1 exhibits high selectivity for SMARCB1 -deficient cancer cells and possesses anti-tumor activity. In addition, the combination of GCLCi1 with SLC7A11 inhibitors and Telaglenastat (HY-12248) produces a synergistic effect, which can be used for the research of smarcb1-deficient malignant rhabdoid tumors and smarcb1-deficient epithelioid sarcomas.
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- No. CAS: 2926699-78-5
- Fòrmula: C8H15F3N2O4S
- Peso molecular:292.28
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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Chemical Information
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Actividad biológica
Descripciòn
In Vitro
GCLCi1 (72 hours) potently and selectively reduces viability in SMARCB1-deficient JMU-RTK-2 cells with an IC50 lower than in SMARCB1-proficient JMU-RTK-2 cells, and has a higher selective index than EZH2 inhibitors[1].
GCLCi1 (tested concentrations; 72 hours) induces ferroptotic cell death in SMARCB1-deficient JMU-RTK-2 cells, as cell death is rescued by the ferroptosis inhibitor Ferrostatin-1 (HY-100579) but not the apoptosis inhibitor Z-VAD-FMK[1].
GCLCi1 (0.1-0.4 µmol/L; 72 hours) induces dose-dependent SLC7A11 mRNA upregulation in SMARCB1-proficient JMU-RTK-2 cells, but this adaptive response is impaired in SMARCB1-deficient JMU-RTK-2 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
GCLCi1 (30 mg/kg; p.o.; 5 days on/2 days off, repeated for one additional 5-day cycle) administered via an intermittent oral gavage regimen does not suppress tumor growth in SMARCB1-proficient renal cancer xenografts, demonstrating selective activity for SMARCB1-deficient tumors[1].
GCLCi1 (10 mg/kg; p.o.; 5 days on/2 days off, repeated for one additional 5-day cycle) administered via an intermittent oral gavage regimen shows significant antitumor efficacy in SMARCB1-deficient rhabdoid tumor xenografts, with enhanced efficacy when combined with telaglenastat[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c-nu/nu (5- to 6-week-old female; subcutaneous xenograft of SMARCB1-deficient JMU-RTK-2 rhabdoid tumor cells)[1]
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Dosage:10 mg/kg; 30 mg/kg
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Administration:p.o.; 5 days on/2 days off, repeated for one additional 5-day cycle
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Result:Significantly suppressed tumor growth compared with vehicle control.
Showed no drug-induced changes in mouse body weight.
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Animal Model:BALB/c-nu/nu (5- to 6-week-old female; subcutaneous xenograft of SMARCB1-proficient VMRC-RCW renal cancer cells)[1]
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Dosage:30 mg/kg
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Administration:p.o.; 5 days on/2 days off, repeated for one additional 5-day cycle
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Result:Showed no antitumor effect on tumor growth compared with vehicle control.
Showed no significant changes in mouse body weight.
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Animal Model:BALB/c-nu/nu (5- to 6-week-old female; subcutaneous xenograft of SMARCB1-deficient JMU-RTK-2 rhabdoid tumor cells)[1]
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Dosage:10 mg/kg (alone); 10 mg/kg + 100 mg/kg telaglenastat (combination)
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Administration:p.o.; 5 days on/2 days off, repeated for one additional 5-day cycle
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Result:Significantly suppressed tumor growth compared with vehicle control when administered alone.
Produced even greater antitumor efficacy when coadministered with telaglenastat than either monotherapy.
Showed no effects on mouse body weight with either single or combined administration.
Chemical Information
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No. CAS 2926699-78-5
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Peso molecular 292.28
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Fòrmula C8H15F3N2O4S
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SMILES
N[C@H](C(O)=O)CCS(=N)(CCC(O)C(F)(F)F)=O
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Synonyms
ONO-7068506
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
GCLCi1 Related Classifications
HY-184267 Related Classifications
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Keywords
- GCLCi1
- 2926699-78-5
- ONO-7068506
- GCLCi 1
- GCLCi-1
- ONO7068506
- ONO 7068506
- glutathione
- lipid peroxidation
- reactive oxygen species
- malignant rhabdoid tumors
- ferroptosis
- GCLC
- mouse tumor xenograft models
- SMARCB1-deficient cancer cells
- glutamate-cysteine ligase catalytic subunit
- epithelioid sarcomas
- Inhibitor
- inhibitor
- inhibit