Glutamate-cysteine ligase inhibitor EN25 is a covalent inhibitor of the glutamate-cysteine ligase (GCL) with IC50 of 16 uM, targets an allosteric cysteine C114 on GCLM, the modifier subunit of GCL.
Glutamate-cysteine ligase inhibitor EN25 inhibits GCL activity, lowers cellular GSH levels, and impairs cell viability in ARID1A-deficient cancer cells that are particularly vulnerable to glutathione depletion, but not in ARID1A-positive cancer cells.