Cpi455

IOX1,
IOX2, ML324, KDMOAM25, succinate,
fumarate, 2OG, dimethylpyridine-2,4-dicarboxylate, dimethyl 2-oxoglutarate,
dimethyl succinate, dimethyl fumarate, and DMOG were purchased from
Sigma-Aldrich, while IOX3, IOX4, Roxadustat, Vadadustat, Panobinostat,
disodium 2S/2R-hydroxyglutarate, and FG0041 were
obtained from Cayman Chemical Company. 2,4-PDCA (Alfa Aesar), Daprodustat
(MedChemExpress), QC6352 (MedChemExpress), Molidustat (Selleck Chem),
JIB-04 (Tocris Bioscience), GSK-J1 (Tocris Bioscience), GSK-J4 (Tocris
Bioscience), SD70 (Xcess Biosciences), CPI455 (Axon Med Chem), 2′-deoxy-5-methylcytidine
(TCI Chemicals), 2′-deoxy-5-(hydroxymethyl)cytidine (TCI Chemicals),
and (R/S)-Octyl-α-hydroxyglutarate
(Cambridge Bioscience) were purchased from other commercial sources.
All purchased inhibitors were >95% pure as determined by the manufacturer.
Key compound purity was verified using analytical HPLC using a UV
detector (210 or 254 nm) or CAD detector (Figures S18–S28). NOG was synthesized as described in the materials
and methods and has a purity >95% as determined by HPLC. All buffer
components were from Sigma-Aldrich unless otherwise stated.

The human GB cell lines A172, U251, CAS1, DBTRG and U87 were obtained from the Biological Bank and Cell Factory of IRCCS AOU San Martino - IST (www.iclc.it) and were grown in DMEM supplemented with 10% FBS and 2 mM L-Glutamine. The authenticity of the cells was certified by the Biological Bank utilizing eight highly polymorphic STR loci plus amelogenin (Cell IDTM, Promega).
GB cultures derived from primary GB, were cultivated in stem-permissive, serum-free medium as previously described [49 (link), 50 (link)]. Cell differentiation was carried out by shifting GBM CSCs in serum-containing medium (10% FBS). TMZ resistance was induced as previously described [12 (link)].
Temozolomide (TMZ) was acquired from Sigma-Aldrich (Milano, Italy), JIB 04 from Tocris (Bristol, UK) or Selleckchem (Munich, Germany) and CPI 455 was from Axon Medchem (Groningen, NL). TMZ and CPI 455 were dissolved in DMSO at 100 and JIB 04 was dissolved in DMSO at 10 mM. All chemicals were stored at −80°C and diluted in culture medium immediately before use.