Lonidamine is a derivative of
indazole-3-carboxylic acid, which for a long time, has been known to inhibit aerobic
glycolysis
Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH ...
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
A hexokinase is an enzyme that phosphorylates hexoses (six-carbon sugars), forming hexose phosphate. In most organisms, glucose is the most important substrate for hexokinases, and glucose-6-phosphate is the most important product. Hexo ...
. 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.
An in-vitro study 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.
A derivative of lonidamine,
gamendazole
Gamendazole is a drug candidate for male contraception. It is an indazole carboxylic acid derived from lonidamine (LND). It has been shown to reduce fertility in male rats without affecting testosterone levels, but human clinical trials have not ...
, is in testing as a possible male
contraceptive pill Oral contraceptives, abbreviated OCPs, also known as birth control pills, are medications taken by mouth for the purpose of birth control.
Female
Two types of female oral contraceptive pill, taken once per day, are widely available:
* The combin ...
.
References
Antineoplastic drugs
Indazoles
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