L4900

Lonidamine

mitochondrial hexokinase inhibitor

• Synonym(s): 1-(2,4-Dichlorobenzyl)-1H-indazole-3-carboxylic acid, Diclondazolic acid
• Empirical Formula (Hill Notation): C₁₅H₁₀Cl₂N₂O₂
• CAS Number: 50264-69-2
• Molecular Weight: 321.16
• EC Number: 256-510-0
• MDL number: MFCD00866285
• UNSPSC Code: 12352202
• PubChem Substance ID: 24278515
• NACRES: NA.77

Properties

• Quality Level: 200
• assay: ≥98% (TLC)
• form: powder
• solubility: chloroform: methanol (1:1): 9.80-10.20 mg/mL, clear, colorless to light yellow
• SMILES string: OC(=O)c1nn(Cc2ccc(Cl)cc2Cl)c3ccccc13
• 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)
• InChI key: WDRYRZXSPDWGEB-UHFFFAOYSA-N

Description

Application

Lonidamine has been used:

• as an inhibitor of glycolysis to study its effects on the epithelial-mesenchymal transition (EMT) mechanism in cancer stem cells (CSC)
• as mitochondrial permeability transition (MPT)- inducing drug to study its effects on temozolomide-resistant glioblastoma cell line
• as mitochondrial hexokinase inhibitor to measure reactive oxygen species (ROS) in human acute myeloid leukemia cells

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.

Lonidamine (LND) is an indazole derivative and is an anti-spermatogenic agent. It exhibits anti-tumor activity by sensitizing tumors to photodynamic, chemo-, radiotherapy, and hyperthermia. LND also interferes with energy metabolism by blocking glycolysis, adenosine diphosphate (ADP-), and uncoupler-stimulated respiration on various nicotinamide adenine dinucleotide (NAD-) and flavin adenine dinucleotide (FAD)-linked substrates, hexokinase activity, and oxygen uptake in Ehrlich ascites tumor cells. It blocks lactate export and pyruvate uptake into the mitochondria by inhibiting proton-linked monocarboxylate transporter (MCT) and mitochondrial pyruvate carrier (MPC), respectively.

Safety Information

• pictograms: GHS08,GHS07
• signalword: Danger
• hcodes: H302,H351,H360
• pcodes: P201 - P301 + P312 + P330 - P308 + P313
• Hazard Classifications: Acute Tox. 4 Oral - Carc. 2 - Repr. 1B
• Storage Class: 6.1C - Combustible acute toxic Cat.3 / toxic compounds or compounds which causing chronic effects
• wgk_germany: WGK 3
• flash_point_f: Not applicable
• flash_point_c: Not applicable
• ppe: Eyeshields, Gloves, type P3 (EN 143) respirator cartridges