2r octyl α hydroxyglutarate

The PARP inhibitor talazoparib (S7048, Selleckchem, Houston, TX, USA), the IDH1 mutant (R132H and R132C) inhibitor AGI-5198 (14624, Cayman Chemical, Ann Arbor, MI, USA), the alkylating agent temozolomide (S1237, Selleckchem) and the Bcl-xL/Bcl-2/Bcl-w inhibitor ABT-737 (S1002, Selleckchem) were dissolved in DMSO. The cell permeable derivative of D-2-HG, (2R)-Octyl-α-hydroxyglutarate (16366, Cayman Chemical), was dissolved in phosphate buffered saline (PBS). Doxorubicin (2 mg/mL in 0.9% NaCl) and cisplatin (1 mg/mL in 0.9% NaCl) were obtained from Leiden University Medical Center (in-house hospital pharmacy) and diluted in PBS. Hydrogen peroxide (H₂O₂) (Merck, Darmstadt, Germany) was also diluted in PBS.

The specific mutant IDH1 inhibitor AGI-5198 (14624, Cayman Chemicals, Michigan, USA) was dissolved in DMSO according to the manufacturer’s instructions and stored in − 20 °C. AGI-5198 was used at a concentration of 10 µM since our group previously showed that this leads to a complete inhibition of D-2HG production [18 (link)]. (2R)-Octyl-α-hydroxyglutarate (16366, Cayman Chemicals), a cell-permeable derivative of D2-HG, was freshly dissolved in PBS before use and used at a final concentration of 250 µM.