Lonidamine
Encyclopedia
Lonidamine is a derivative of indazole-3-carboxylic acid, which for a long time, has been known to inhibit aerobic glycolysis
in cancer cells. It seems to enhance aerobic glycolysis in normal cells, but suppress glycolysis in cancer cells. This is most likely through the inhibition of the mitochondrially bound hexokinase
. Later studies in Ehrlich ascites tumor cells showed that lonidamine inhibits both respiration and glycolysis leading to a decrease in cellular ATP.
Clinical trials of lonidamine in combination with other anticancer agents for a variety of cancers has begun. This is due to its proven ability to inhibit energy metabolism in cancer cells, and to enhance the activity of anticancer agents.
Lonidamine has been used in the treatment of brain tumours in combination with radiotherapy and temozolomide. Results showed that a combination of temozolomide and lonidamine at clinically achievable, low plasma concentrations, could inhibit tumour growth, and lonidamine could reduce the dose of temozolomide required for radiosensitization of brain tumours.
Male contraceptive use: "also in the works is a contraceptive nasal spray for men that combines an anti-cancer derivative, lonidamine, with an isolated hormone precursor from insect cells."
Glycolysis
Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+...
in cancer cells. It seems to enhance aerobic glycolysis in normal cells, but suppress glycolysis in cancer cells. This is most likely through the inhibition of the mitochondrially bound hexokinase
Hexokinase
A hexokinase is an enzyme that phosphorylates a six-carbon sugar, a hexose, to a hexose phosphate. In most tissues and organisms, glucose is the most important substrate of hexokinases, and glucose-6-phosphate the most important product....
. Later studies in Ehrlich ascites tumor cells showed that lonidamine inhibits both respiration and glycolysis leading to a decrease in cellular ATP.
Clinical trials of lonidamine in combination with other anticancer agents for a variety of cancers has begun. This is due to its proven ability to inhibit energy metabolism in cancer cells, and to enhance the activity of anticancer agents.
Lonidamine has been used in the treatment of brain tumours in combination with radiotherapy and temozolomide. Results showed that a combination of temozolomide and lonidamine at clinically achievable, low plasma concentrations, could inhibit tumour growth, and lonidamine could reduce the dose of temozolomide required for radiosensitization of brain tumours.
Male contraceptive use: "also in the works is a contraceptive nasal spray for men that combines an anti-cancer derivative, lonidamine, with an isolated hormone precursor from insect cells."