ERG245

ERG245 is a highly selective, potent small-molecule inhibitor of cytosolic branched-chain amino acid transaminase 1 (BCAT1), with an IC50 of approximately 0.5 nM and over 2000-fold selectivity over BCAT2. Developed by Ergon Pharmaceuticals, ERG245 blocks the enzymatic activity of BCAT1, which is responsible for the reversible transamination of branched-chain amino acids (BCAAs) like leucine. In oncology, ERG245 has demonstrated therapeutic potential in T-cell acute lymphoblastic leukemia (T-ALL) by disrupting the DNA damage response (DDR) and synergizing with DNA-damaging agents like etoposide. Additionally, ERG245 has been investigated in immuno-oncology, where temporal inhibition of BCAT1 alters mitochondrial iron homeostasis, enhances oxidative phosphorylation (OXPHOS) in CD8+ T cells, and reverses terminal T-cell exhaustion, thereby boosting the efficacy of anti-PD-1 checkpoint inhibitors. It also shows potential in inflammatory conditions such as colitis and in solid tumors like hepatocellular carcinoma (HCC).