Discovery of novel BCAT2 inhibitors: design, synthesis, in vitro evaluation, and molecular modeling studies

Key Points

• The aim is to discover and evaluate new inhibitors of the BCAT2 enzyme, which is involved in amino acid metabolism.
• Utilized structure-based rational design to create novel inhibitors.
• Conducted in vitro evaluation to determine inhibitor potency and selectivity against BCAT1 and BCAT2.
• Performed molecular modeling studies to analyze binding interactions within the enzyme's active site.
• Identified C10 and C11 as potent BCAT2 inhibitors with IC50 values of 44 nM and 54 nM, respectively.
• Demonstrated 8–10-fold selectivity of these inhibitors over BCAT1.
• Confirmed stable interactions between inhibitors and the BCAT2 active pocket.