Lonidamine

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Lonidamine
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Clinical data
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Identifiers
  • 1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid
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Chemical and physical data
FormulaC15H10Cl2N2O2
Molar mass321.16 g·mol−1
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  • C1=CC=C2C(=C1)C(=NN2CC3=C(C=C(C=C3)Cl)Cl)C(=O)O
  • InChI=1S/C15H10Cl2N2O2/c16-10-6-5-9(12(17)7-10)8-19-13-4-2-1-3-11(13)14(18-19)15(20)21/h1-7H,8H2,(H,20,21) ☒N
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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.[1]

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.[1]

Lonidamine has been used in the treatment of brain tumours in combination with radiotherapy and temozolomide.[2] 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.[2]

A derivative of lonidamine, gamendazole, is in testing as a possible male contraceptive pill.[3]

References

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  1. ^ a b Page Module:Citation/CS1/styles.css has no content.Pelicano H, Martin DS, Xu RH, Huang P (August 2006). "Glycolysis inhibition for anticancer treatment". Oncogene. 25 (34): 4633–4646. doi:10.1038/sj.onc.1209597. PMID 16892078.
  2. ^ a b Page Module:Citation/CS1/styles.css has no content.Prabhakara S, Kalia VK (August 2008). "Optimizing radiotherapy of brain tumours by a combination of temozolomide & lonidamine" (PDF). Indian J. Med. Res. 128 (2): 140–8. PMID 19001677.
  3. ^ Page Module:Citation/CS1/styles.css has no content.Tash, Joseph (July 2008). "A Novel Potent Indazole Carboxylic Acid Derivative Blocks Spermatogenesis and Is Contraceptive in Rats after a Single Oral Dose". Biology of Reproduction. 78 (6): 1127–1138. doi:10.1095/biolreprod.106.057810. PMID 18218612.

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