Lonidamine

Lonidamine
	File:Lonidamine.svg
Clinical data
ATC code	L01XX07 (WHO) ;
Identifiers
	IUPAC name 1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid;
CAS Number	50264-69-2 ;
PubChem CID	39562;
ChemSpider	36170;
UNII	U78804BIDR;
KEGG	D07257 ;
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
Formula	C15H10Cl2N2O2
Molar mass	321.158 g/mol
3D model (JSmol)	Interactive image;
	SMILES C1=CC=C2C(=C1)C(=NN2CC3=C(C=C(C=C3)Cl)Cl)C(=O)O;
	InChI 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); Key:WDRYRZXSPDWGEB-UHFFFAOYSA-N;
(verify)

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. 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.^[2]

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

References

↑ ^1.0 ^1.1 Pelicano H, Martin DS, Xu RH, Huang P (August 2006). "Glycolysis inhibition for anticancer treatment" (PDF). Oncogene. 25 (34): 4633–4646. doi:10.1038/sj.onc.1209597. PMID 16892078.
↑ 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.
↑ 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. |access-date= requires |url= (help)

Template:Antineoplastic-drug-stub

[pmid16892078-1] 1.0 ^1.1 Pelicano H, Martin DS, Xu RH, Huang P (August 2006). "Glycolysis inhibition for anticancer treatment" (PDF). Oncogene. 25 (34): 4633–4646. doi:10.1038/sj.onc.1209597. PMID 16892078.

[pmid19001677-2] 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.

[Tash-3] 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. |access-date= requires |url= (help)

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[2]

[3]

v t e Chemotherapeutic agents/Antineoplastic agents (L01)
Alkylating and alkylating-like agents	Nitrogen mustards: (Chlorambucil, Chlormethine, Cyclophosphamide, Ifosfamide, Melphalan, Bendamustine, Uramustine) Nitrosoureas:(Carmustine, Fotemustine, Lomustine, Streptozocin) Platinum (alkylating-like): (Carboplatin, Cisplatin, Oxaliplatin, Triplatin tetranitrate, Satraplatin) Alkyl sulfonates:(Busulfan, Treosulfan) Hydrazines:(Procarbazine, Dacarbazine, Temozolomide) Aziridines:(ThioTEPA)
Antimetabolites	Folic acid: (Aminopterin, Methotrexate, Pemetrexed, Raltitrexed). Purine:(Cladribine, Clofarabine, Fludarabine, Mercaptopurine, Pentostatin, Thioguanine) Pyrimidine:(Capecitabine, Cytarabine, Decitabine, Fluorouracil, Floxuridine, Gemcitabine)
Spindle poison/mitotic inhibitor	Taxane: (Docetaxel, Larotaxel, Paclitaxel). Vinca: (Vinblastine, Vincristine, Vindesine, Vinorelbine).
Cytotoxic/antitumor antibiotics	Anthracycline family: (Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Mitoxantrone, Pixantrone, Valrubicin) streptomyces (Actinomycin, Bleomycin, Mitomycin, Plicamycin) - Hydroxyurea
Topoisomerase inhibitors	Camptotheca: (Camptothecin, Topotecan, Irinotecan, Rubitecan), Podophyllum:(Etoposide, Teniposide)
CI monoclonal antibodies	Receptor tyrosine kinase (Cetuximab, Panitumumab, Trastuzumab) - CD20 (Rituximab, Tositumomab) - other (Alemtuzumab, Bevacizumab, Gemtuzumab)
Photosensitizers	Aminolevulinic acid, Methyl aminolevulinate, Porfimer sodium, Verteporfin
Tyrosine kinase inhibitors	Axitinib, Bosutinib, Cediranib, Dasatinib, Erlotinib, Gefitinib, Imatinib, Lapatinib, Lestaurtinib, Nilotinib, Semaxanib, Sorafenib, Sunitinib, Vandetanib
Cyclin-dependent kinase inhibitor	Seliciclib
Other	retinoids (Alitretinoin, Tretinoin), Fusion protein (Aflibercept) - Altretamine, Amsacrine, Anagrelide, Arsenic trioxide, Asparaginase (Pegaspargase), Bexarotene, Bortezomib, Celecoxib, Denileukin diftitox, Elesclomol, Estramustine, Irofulven, Ixabepilone, Masoprocol, Mitotane, Oblimersen, Testolactone, Tipifarnib, Trabectedin

Clinical data
File:Lonidamine.svg
ATC code	L01XX07 (WHO)
Identifiers
IUPAC name 1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid
CAS Number	50264-69-2^Y
PubChem CID	39562
ChemSpider	36170
UNII	U78804BIDR
KEGG	D07257^Y
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
Formula	C₁₅H₁₀Cl₂N₂O₂
Molar mass	321.158 g/mol
3D model (JSmol)	Interactive image
SMILES C1=CC=C2C(=C1)C(=NN2CC3=C(C=C(C=C3)Cl)Cl)C(=O)O
InChI 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) Key:WDRYRZXSPDWGEB-UHFFFAOYSA-N
(verify)

Lonidamine

References

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