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Cat. No.: HY-184267

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GCLCi1

Name: GCLCi1
Brand: MedChemExpress
SKU: HY-184267
Availability: PreOrder

(Synonyms: ONO-7068506)

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.

For research use only. We do not sell to patients.

CAS No.: 2926699-78-5
Formula: C₈H₁₅F₃N₂O₄S
Molecular Weight:292.28

Storage:

Please store the product under the recommended conditions in the Certificate of Analysis.

GCLCi1 Chemical Structure

CAS No.: 2926699-78-5

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Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- In Vitro
- In Vivo
Chemical Information
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Biological Activity

Description

In Vitro

Anti-cancerFerroptosis

Anti-cancer

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].

Ferroptosis

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].

Anti-cancer

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

Anti-cancer

GCLCi1 (10-30 mg/kg; p.o.; 5 days on/2 days off, repeated for one additional 5-day cycle) administered via an intermittent oral gavage regimen produces significant, well-tolerated antitumor efficacy in SMARCB1-deficient rhabdoid tumor xenografts^[1].

Anti-cancer

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].

Anti-cancer

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.

Animal Model:

BALB/c-nu/nu (5- to 6-week-old female; subcutaneous xenograft of SMARCB1-deficient JMU-RTK-2 rhabdoid tumor cells)^[1]
Dosage:

10 mg/kg; 30 mg/kg
Administration:

p.o.; 5 days on/2 days off, repeated for one additional 5-day cycle
Result:

Significantly suppressed tumor growth compared with vehicle control.
Showed no drug-induced changes in mouse body weight.

Animal Model:

BALB/c-nu/nu (5- to 6-week-old female; subcutaneous xenograft of SMARCB1-proficient VMRC-RCW renal cancer cells)^[1]
Dosage:

30 mg/kg
Administration:

p.o.; 5 days on/2 days off, repeated for one additional 5-day cycle
Result:

Showed no antitumor effect on tumor growth compared with vehicle control.
Showed no significant changes in mouse body weight.

Animal Model:

BALB/c-nu/nu (5- to 6-week-old female; subcutaneous xenograft of SMARCB1-deficient JMU-RTK-2 rhabdoid tumor cells)^[1]
Dosage:

10 mg/kg (alone); 10 mg/kg + 100 mg/kg telaglenastat (combination)
Administration:

p.o.; 5 days on/2 days off, repeated for one additional 5-day cycle
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.

Related Protocols :

Chemical Information

CAS No. 2926699-78-5
Molecular Weight 292.28
Formula C₈H₁₅F₃N₂O₄S
SMILES

N[C@H](C(O)=O)CCS(=N)(CCC(O)C(F)(F)F)=O
Synonyms

ONO-7068506
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation

Handling Instructions (2659 KB)

References

[1]. Takeuchi M, et al.. A GCLC Inhibitor Enhances the Antitumor Efficacy of Glutathione Metabolic Pathway Inhibition in SMARCB1-Deficient Rhabdoid Tumors. Cancer research. 2026 Jun 15;86(12):2990-3004. [Content Brief]

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Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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100 mg

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Biological Activity
- Description
- In Vitro
- In Vivo
Chemical Information
Purity & Documentation
References

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GCLCi1