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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