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Hexokinase inhibitors block the enzymes that phosphorylate glucose in the first step of glycolysis. Mammals express four hexokinase isozymes, and hexokinases I to III are inhibited by their product, glucose-6-phosphate. Hexokinase IV is covered separately in the sibling Glucokinase category. Hexokinase 2 (HK2) binds the outer mitochondrial membrane and is highly expressed in many tumors. A 2013 mouse study found HK2 to be required for tumor initiation and maintenance in lung and breast cancer models. 2-Deoxy-D-glucose is a glucose analog that is phosphorylated but not metabolized further. 3-Bromopyruvic acid and HK-2-IN-1 are listed as HK2 inhibitors, and C-02 is a proteolysis-targeting chimera that degrades HK2.
