| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 250mg |
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Purity: ≥98%
Lonidamine (AF 1890, Diclondazolic Acid) is an orally bioactive small molecule inhibitor of hexokinase, also inhibits mitochondrial pyruvate carrier (Ki 2.5 μM in isolated rat liver mitochondria) and plasma membrane monocarboxylate transporters. Lonidamine reduces the oxygen consumption in both normal and neoplastic cells, while it increases the aerobic glycolysis of normal cells but inhibited that of tumor cells. Lonidamine induces the permeabilization of ANT proteoliposomes in a cell-free system, yet has no effect on protein-free liposomes. Lonidamine adds to synthetic planar lipid bilayers containing ANT, eliciting ANT channel activities with clearly distinct conductance levels. Lonidamine provokes a disruption of the mitochondrial transmembrane potential which precedes signs of nuclear apoptosis and cytolysis.
| ln Vitro |
In AKR-2B and TIG-1 cells, lonsidine (100 μM, 24 h) suppresses the rate of oxygen consumption and lactate generation induced by TGF-β[3]. Lonidamine (100 μM, 24/48 h) suppresses the growth of A549 and H2030BrM3 cells[4]. A549 and H2030BrM3 cell invasion is inhibited by lonsidamine (100–200 μM, 24 h)[4]. Inhibiting the activities of mitochondrial complex I and II, lonsidamine (100-1000 μM, 24 h) is used[4]. In H2030BrM3 lung cancer cells, lonsidamine (200 μM, 24 h) enhances ROS generation[4].
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| ln Vivo |
In a mouse model of BLM-induced pulmonary fibrosis, lonsamine (oral treatment, 10-100 mg/kg/day, d10 to d20) enhances lung function by blocking hexokinase 2 (HK2) activity[3].
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| Animal Protocol |
Animal/Disease Models: Lonidamine (oral administration, 10 -100 mg/kg/day, d10 to d20) improves lung function by inhibiting hexokinase 2 (HK2) activity in BLM-induced pulmonary fibrosis murine model[3].
Doses: 10, 30, 100 mg/kg/day Route of Administration: Oral administration, daily, d10 to d20 after BLM treatment. Experimental Results: Partially or completely reversed the increases in HK2 and lactate induced by BLM and decreased the expression of 10 profibrotic mediators. |
| ADME/Pharmacokinetics |
Metabolism / Metabolites
Lonidamine has known human metabolites that include (2S,3S,4S,5R)-6-[1-[(2,4-Dichlorophenyl)methyl]indazole-3-carbonyl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid. |
| References |
[1]. Nancolas B, et al. The anti-tumour agent lonidamine is a potent inhibitor of the mitochondrial pyruvate carrier and plasma membrane monocarboxylate transporters. Biochem J. 2016 Apr 1;473(7):929-36.
[2]. Ilya A Shutkov, et al. Ru(III) Complexes with Lonidamine-Modified Ligands. Int J Mol Sci. 2021 Dec 15;22(24):13468. [3]. Xueqian Yin, et al. Hexokinase 2 couples glycolysis with the profibrotic actions of TGF-β. Sci Signal. 2019 Dec 17;12(612):eaax4067. [4]. Gang Cheng, et al. Targeting lonidamine to mitochondria mitigates lung tumorigenesis and brain metastasis. Nat Commun. 2019 May 17;10(1):2205. |
| Additional Infomation |
Lonidamine is a member of the class of indazoles that is 1H-indazole that is substituted at positions 1 and 3 by 2,4-dichlorobenzyl and carboxy groups, respectively. It has a role as an antispermatogenic agent, an antineoplastic agent, a geroprotector and an EC 2.7.1.1 (hexokinase) inhibitor. It is a member of indazoles, a dichlorobenzene and a monocarboxylic acid.
Lonidamine (LND) is a drug that interferes with energy metabolism of cancer cells, principally inhibiting aerobic glycolytic activity, by its effect on mitochondrially-bound hexokinase (HK). In such way LND could impair energy-requiring processes, as recovery from potentially lethal damage, induced by radiation treatment and by some cytotoxic drugs. Lonidamine is an indazole carboxylic acid derivative that exhibits radiosensitizing and antiparasitic effects and interferes with the multidrug resistance mechanism. Drug Indication Investigated for use/treatment in benign prostatic hyperplasia, prostate disorders, and cancer/tumors (unspecified). Mechanism of Action Lonidamine is an orally administered small molecule that inhibits glycolysis by the inactivation of hexokinase. Hexokinase is an enzyme that catalyzes glucose, the first step in glycolysis. The inhibition of hexokinase by lonidamine is well established. In addition, there is evidence that lonidamine may increase programmed cell death. This stems from the observation that mitochondria and mitochondria-bound hexokinase are crucial for induction of apoptosis; agents that directly effect mitochondria may, therefore, trigger apoptosis. Indeed, in vitro models with lonidamine exhibit the hallmarks of apoptosis, including mitochondrial membrane depolarization, release of cytochrome C, phosphatidylserine externalization, and DNA fragmentation. [PMID: 16986057] |
| Molecular Formula |
C15H10CL2N2O2
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| Molecular Weight |
321.16
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| Exact Mass |
320.011
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| CAS # |
50264-69-2
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| Related CAS # |
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| PubChem CID |
39562
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
537.9±45.0 °C at 760 mmHg
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| Melting Point |
207-209°C
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| Flash Point |
279.1±28.7 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.678
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| LogP |
4.32
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
21
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| Complexity |
396
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C([H])=C(C([H])=C([H])C=1C([H])([H])N1C2=C([H])C([H])=C([H])C([H])=C2C(C(=O)O[H])=N1)Cl
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| InChi Key |
WDRYRZXSPDWGEB-UHFFFAOYSA-N
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| InChi Code |
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)
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| Chemical Name |
1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.48 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.48 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1137 mL | 15.5686 mL | 31.1371 mL | |
| 5 mM | 0.6227 mL | 3.1137 mL | 6.2274 mL | |
| 10 mM | 0.3114 mL | 1.5569 mL | 3.1137 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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