50264-69-2

Basic information

• Product Name: Lonidamine
• Synonyms: af1890;dica;doridamina;DICLONDAZOLIC ACID;LONIDAMINE;1-[2,4-DICHLOROBENZYL]-1H-INDAZOLE-3-CARBOXYLIC ACID;1-[(2,4-DICHLOROPHENYL)METHYL]-1H-INDAZOLE-3-CARBOXYLIC ACID;1-(2,4-Dichlorobenzyl)indazole-3-carboxylic acid
• CAS NO: 50264-69-2
• Molecular Formula: C₁₅H₁₀Cl₂N₂O₂
• Molecular Weight: 321.16
• EINECS: 256-510-0
• Product Categories: API;DORIDAMINA;inhibitor;Anti-cancer&immunity
• Mol File: 50264-69-2.mol
• Article Data: 10

Chemical Properties

• Melting Point: 207-209°C
• Boiling Point: 537.9 °C at 760 mmHg
• Flash Point: 280.6 °C
• Appearance: white to light yellow crystal
• Density: 1.4835 (rough estimate)
• Vapor Pressure: 2.11E-12mmHg at 25°C
• Refractive Index: 1.6070 (estimate)
• Storage Temp.: Store at RT
• Solubility: Soluble in DMSO (up to 25 mg/ml).
• PKA: 3.00±0.10(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 1 month.
• CAS DataBase Reference: Lonidamine(CAS DataBase Reference)
• NIST Chemistry Reference: Lonidamine(50264-69-2)
• EPA Substance Registry System: Lonidamine(50264-69-2)

Safety Data

• Hazard Codes: T
• Statements: 60-22-40
• Safety Statements: 53-22-36/37/39-45
• WGK Germany: 3
• RTECS: NK7886000
• Hazardous Substances Data: 50264-69-2(Hazardous Substances Data)

Usage

Description

Lonidamine, also known as Doridamina, is a derivative of indazole-3-carboxylic acid and an orally administrated small molecule. It is a member of the class of indazoles, specifically 1H-indazole substituted at positions 1 and 3 by 2,4-dichlorobenzyl and carboxy groups, respectively. Lonidamine inhibits the glycolysis process by inactivating hexokinase, the first step in glycolysis. This property makes it a potential candidate for cancer treatment, as cancer cells primarily generate energy through glycolysis. Additionally, Lonidamine has been shown to enhance aerobic glycolysis in normal cells while inhibiting glycolysis in cancer cells and increasing the occurrence of apoptosis. It has also demonstrated effectiveness in the treatment of benign prostatic hyperplasia (BPH).

Uses

Used in Anticancer Applications:
Lonidamine is used as an antineoplastic agent for the treatment of various cancers, including lung, breast, prostate, and brain tumors. Its clinical effect is associated with changes in cellular energy metabolism, specifically by inhibiting glycolysis in cancer cells and enhancing aerobic glycolysis in normal cells.
Used in Contraceptive Applications:
Lonidamine is used as a contraceptive agent, potentially due to its ability to inhibit glycolysis, which may affect sperm cell energy production and function.
Used in Spermicidal Applications:
Lonidamine is used as a spermicidal agent, likely because of its inhibitory effect on glycolysis, which could disrupt sperm cell energy metabolism and reduce their viability.

References

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1477623/ https://en.wikipedia.org/wiki/Lonidamine

References

1) Gatto?et al. (2002),?Recent studies on lonidamine, the lead compound of the antispermatogenic indazol-carboxylic acids; Contraception,?65?277 2) Floridi?et al., (1981),?Effect of Lonidamine on the Energy Metabolism of Ehrlich Ascites Tumor Cells; Cancer Res.,?41?4661 3) Ravagnan?et al. (1999),?Lonidamine triggers apoptosis via a direct, Bcl-2-inhibited effect on the mitochondrial permeability transition pore; Oncogene,?18?2537 4) Ben-Horin?et al. (1995),?Mechanism of Action of the Antineoplastic Drug Lonidamine: 31P and 13C Nuclear Magnetic Resonance Studies; Cancer Res.?55?2814 5) Nath?et al. (2016),?Mechanism of antineoplastic activity of lonidamine; Biochim.Biophys.Acta Reviews on Cancer?1866?151

Originator

Angelini (Italy)

Biological Activity

Anticancer and antispermatogenic agent in vitro and in vivo . Inhibits cellular energy metabolism in some cells via inhibition of mitochondrial hexokinase. Also blocks CFTR Cl - channels in vitro .

Biochem/physiol Actions

Inhibits the energy metabolism of neoplastic cells by interfering with hexokinase and disrupting uncoupler-stimulated mitochondrial electron transport; damages cell and mitochondrial membranes.

InChI:InChI=1/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)

Upstream product

• 252025-50-6 methyl 1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylate 
• 94-99-5 2,4-Dichlorobenzyl chloride 
• 43120-28-1 methyl 1H-indazole-3-carboxylate 
• 2142-69-0 2-bromophenyl methyl ketone 
• 99233-20-2 α-hydroxy-2-bromoacetophenone 
• 64132-13-4 3-(hydroxymethyl)-1H-indazole 
• 920019-58-5 (1-(2,4-dichlorobenzyl)-1H-indazol-3-yl)methanol 
• 4498-67-3 1H-Indazole-3-carboxylic acid 
• 20443-99-6 2,4-dichlorobenzyl bromide 

Downstream Products

• 875577-70-1 C₂₄H₂₂Cl₂N₂O₈ 
• 874110-84-6 1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic chloride 
• 50264-84-1 ethyl lonidamine 
• 252025-50-6 methyl 1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylate 

Relevant articles and documents

Multiaction Platinum(IV) Prodrug Containing Thymidylate Synthase Inhibitor and Metabolic Modifier against Triple-Negative Breast Cancer

Multifunctional platinumIV anticancer prodrugs have the potential to enrich the anticancer properties and overcome the clinical problems of drug resistance and side effects of platinumII anticancer agents. Herein, we develop dual and triple action platinumIV complexes with targeted and biological active functionalities. One complex (PFL) that consists of cisplatin, tegafur, and lonidamine exhibits strong cytotoxicity against triple negative breast cancer (TNBC) cells. Cellular uptake and distribution studies reveal that PFL mainly accumulates in mitochondria. As a result, PFL disrupts the mitochondrial ultrastructure and induces significant alterations in the mitochondrial membrane potential, which further leads to an increase in production of reactive oxygen species (ROS) and a decrease in ATP synthesis in MDA-MB-231 TNBCs. Western blot analysis reveals the formation of ternary complex of thymidylate synthase, which shows the intracellular conversion of tegafur into 5-FU after its release from PFL. Furthermore, treatment with PFL impairs the mitochondrial function, leading to the inhibition of glycolysis and mitochondrial respiration and induction of apoptosis through the mitochondrial pathway. The RNA-sequencing experiment shows that PFL can perturb the pathways involved in DNA synthesis, DNA damage, metabolism, and transcriptional activity. These findings demonstrate that PFL intervenes in several cellular processes including DNA damage, thymidylate synthase inhibition, and perturbation of the mitochondrial bioenergetics to kill the cancer cells. The results highlight the significance of a triple-action prodrug for efficient anticancer therapy for TNBCs.

Preparation methods of 1H-indazol-3-carboxylic acid derivative, granisetron and lonidamine

The invention relates to preparation methods of a 1H-indazol-3-carboxylic acid derivative, granisetron and lonidamine. The 1H-indazol-3-carboxylic acid derivative is a compound with a structure shown in a formula (1) and a formula (2), and is mainly structurally characterized by having a 1H-indazol-3-carboxylic acid amide skeleton and a 1H-indazol-3-carboxylic ester skeleton. The 1H-indazol-3-carboxylic acid derivative can be synthesized by taking simple o-aminophenylacetic acid amide or o-aminophenylacetic acid ester as an initial raw material. The 1H-indazol-3-carboxylic acid derivative is a key intermediate for synthesizing a plurality of medicines, such as granisetron, lonidamine and the like. The synthesis method of the 1H-indazol-3-carboxylic acid derivative and the drug molecules glassetron and lonidamine is simple, the reaction condition is mild, the reaction speed is high, the yield is high, and purification is easy.

Sulfocoumarin-, Coumarin-, 4-Sulfamoylphenyl-Bearing Indazole-3-carboxamide Hybrids: Synthesis and Selective Inhibition of Tumor-Associated Carbonic Anhydrase Isozymes IX and XII

A series of sulfocoumarin-, coumarin-, and 4-sulfamoylphenyl-bearing indazole-3-carboxamide hybrids were synthesized and investigated as inhibitors of the human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms I and II (cytosolic isozymes), as well as hCA IX and XII (transmembrane, tumor-associated enzymes). Compounds 6 a–g (amide derivatives) and 7 a–h (triazoles) act as “prodrugs”, and their hydrolysis products are the de facto CA inhibitors. These compounds displayed sub-micromolar to high-nanomolar inhibitory activity against hCA isoforms IX and XII, which were recently validated as antitumor drug targets. Moreover, no inhibition of the off-target hCA I and II isoforms was observed. Compounds 8 a–f (another set of triazoles) exhibited nanomolar inhibition against hCA isoforms I, II, IX and XII, among which compounds 8 c, 8 d, and 8 f were found to inhibit the tumor-associated hypoxia-induced hCA isoform IX with Ki values of 1.8, 2.3, and 2.0 nm respectively. Further exploration of these compounds could be useful for the development of novel antitumor agents with selective mechanisms of CA inhibitory action.