Hexokinase

Lonidamine (AF-1890), an antitumor agent, is a hexokinase, mitochondrial pyruvate carrier (Ki 2.5 μM in isolated rat liver mitochondria) and plasma membrane monocarboxylate transporters inhibitor, which also inhibits mitochondrial complex II.

2-Deoxy-D-glucose is a glucose analog that acts as a competitive inhibitor of glucose metabolism, inhibiting glycolysis via its actions on hexokinase.

3-Bromopyruvic acid is a hexokinase II inhibitor, is an effective antitumor agent on the hepatoma cells.

C-02 is a PROTAC molecule composed of the hexokinase inhibitor lonidamine linked to the cereblon ligand thalidomide. It selectively degrades hexokinase 2 in 786-O and PANC-1 cells at 20 µM. C-02 exhibits cytotoxicity across multiple cancer cell lines, with IC₅₀ values of 34.07 µM (786-O), 5.08 µM (4T1), 31.53 µM (PANC-1), 6.11 µM (HGC-27), and 21.65 µM (MCF-7), supporting its use in cancer metabolism research.