| Size | Price | |
|---|---|---|
| Other Sizes |
| Targets |
Ditolylguanidine is a non-selective agonist of sigma receptors, targeting both the σ₁ and σ₂ receptor subtypes. The compound binds to σ₁ receptors with a Ki value of 69 nM and to σ₂ receptors with a Ki value of 21 nM. Sigma receptors are a unique class of proteins that are distinct from classical opioid, adrenergic, or dopamine receptors. They are expressed in various tissues, including the central nervous system, immune system, and cancer cells. The σ₁ receptor is involved in the modulation of ion channels, neurotransmitter release, and neuroprotection, while the σ₂ receptor is associated with cell proliferation and apoptosis. Ditolylguanidine's interaction with dopamine drugs has been studied in Wistar rats and Albino Swiss mice. The compound's ability to inhibit small cell lung cancer cell growth is attributed to its σ₂ receptor-mediated effects.
|
|---|---|
| ln Vitro |
Methylguanidine (39-60 nM) has a Ki value of 40 nM and quantitatively inhibits N-(2-piperidinylethyl)4-iodobenzamide [2]. The xylguanidine (0-10 μM) σ1 and σ2 adsorption have Ki values of 69 and 21 nM, respectively [4], and IC50 values of 100 and 90 nM, respectively [3].
In vitro, Ditolylguanidine has been shown to effectively inhibit the growth of small cell lung cancer cells. This antiproliferative effect is attributed to its activity at sigma receptors, particularly the σ₂ receptor subtype, which is known to play a role in cell proliferation and apoptosis. The compound's binding affinity for σ₁ and σ₂ receptors has been well characterized using radioligand binding assays. The compound's effects on cancer cell lines, including small cell lung carcinoma, have been studied to understand the role of sigma receptors in cancer biology and to develop potential anticancer therapies. In addition to its anticancer effects, the compound is used as a pharmacological tool to study sigma receptor-mediated signaling pathways. |
| ln Vivo |
Micturition thresholds and intervals during anesthesia are impacted by methylguanidine (IV; 1–5 mg/kg once) [1]. Intraventricular dose of 1 μg ditoluene raises the anesthesia urination interval and threshold, as well as prolongs the anesthesia urination interval [1].
In vivo, Ditolylguanidine has been studied for its interactions with dopamine drugs in Wistar rats and Albino Swiss mice. The compound's effects on sigma receptors in the central nervous system have been investigated in relation to neuropsychiatric disorders. However, detailed in vivo efficacy data for Ditolylguanidine beyond its use as a research tool are limited. The compound is primarily used in animal models to study sigma receptor pharmacology and to validate sigma receptors as drug targets. Its use in cancer models has also been explored, given its antiproliferative effects on cancer cells. |
| Enzyme Assay |
For in vitro receptor binding studies, Ditolylguanidine is used as a radioligand or as a competitor in sigma receptor binding assays. Membranes from tissues or cells expressing sigma receptors are prepared and incubated with a radiolabeled sigma receptor ligand, such as [³H]DTG (which is Ditolylguanidine itself) or [³H](+)-pentazocine, in the presence of varying concentrations of unlabeled Ditolylguanidine. After incubation, bound and free radioligand are separated, and radioactivity is counted. Competition binding curves are generated to determine the Ki values for σ₁ and σ₂ receptors. For functional studies, Ditolylguanidine is used to activate sigma receptors, and downstream signaling events such as calcium mobilization, kinase activation, or changes in cell proliferation are measured.
|
| Cell Assay |
For in vitro cell-based assays, cancer cell lines, particularly small cell lung cancer cells (e.g., NCI-H69, NCI-H82), are cultured in appropriate media and treated with Ditolylguanidine at various concentrations (typically 0.1-100 μM). Cell viability is measured using MTT, CCK-8, or trypan blue exclusion assays. Apoptosis is assessed by Annexin V staining, caspase activity assays, or DNA fragmentation analysis. Cell cycle distribution is analyzed by flow cytometry. The compound's effects on cell proliferation and survival are evaluated to understand the role of sigma receptors in cancer. For mechanistic studies, the expression of sigma receptors and downstream signaling proteins is analyzed by Western blotting or qPCR.
|
| Animal Protocol |
Animal/Disease Models: Male Std-Wistar rats anesthetized with urethane [1]
Doses: 1-5 mg/kg Route of Administration: intravenous (iv) (iv)injection; pressure [1]. 1-5 mg/kg once Experimental Results: Dose-dependent prolongation of micturition interval and increase in threshold pressure. The micturition reflex and dribbling are eliminated at the 5 mg/kg dose. For in vivo animal studies, Ditolylguanidine is typically administered intraperitoneally or orally in rodent models. In studies investigating its interactions with dopamine drugs, the compound is co-administered with dopaminergic agents, and behavioral responses (e.g., locomotor activity, stereotypy) are assessed. In cancer models, tumor-bearing mice are treated with Ditolylguanidine, and tumor growth is monitored. The compound's effects on sigma receptor-mediated behaviors and physiological functions are evaluated. Pharmacokinetic and biodistribution studies may also be performed to determine the compound's tissue distribution and elimination. Tissue samples are collected for analysis of drug concentrations and receptor occupancy. |
| ADME/Pharmacokinetics |
Ditolylguanidine is a small molecule with a molecular weight of 239.32. It is soluble in DMSO (48 mg/mL) and ethanol (12 mg/mL) but insoluble in water. For in vivo administration, the compound can be formulated in 5% DMSO + 40% PEG300 + 5% Tween 80 + 50% ddH₂O to achieve a concentration of 2.4 mg/mL. Detailed pharmacokinetic parameters, including half-life, bioavailability, and metabolism, have not been extensively characterized in the literature. As a lipophilic compound with a guanidine moiety, it is expected to have reasonable oral bioavailability and tissue distribution, including penetration into the central nervous system given its activity at sigma receptors.
|
| Toxicity/Toxicokinetics |
Specific toxicity data for Ditolylguanidine are limited. The compound is used as a research tool and is not intended for human therapeutic use. At pharmacological doses, it has been reported to be well-tolerated in animal studies. However, as with any research chemical, standard safety precautions should be observed when handling the compound. The compound may cause skin and eye irritation and should be handled in a well-ventilated area with appropriate personal protective equipment. Comprehensive toxicological studies, including genotoxicity and carcinogenicity assessments, have not been published.
|
| References |
|
| Additional Infomation |
1,2-Bis(2-methylphenyl)guanidine is a member of the toluene class of compounds.
Ditolylguanidine is primarily used as a pharmacological tool for studying sigma receptor function. It is the prototypical sigma receptor agonist and is widely used to characterize sigma receptor binding and signaling. The compound has been instrumental in identifying the distinct pharmacological profiles of σ₁ and σ₂ receptors. Its ability to inhibit small cell lung cancer cell growth has made it a valuable tool in cancer research. Ditolylguanidine has no clinical trial or regulatory approval status as a drug. It is commercially available from research chemical suppliers for laboratory use only. The compound is also used as a vulcanization accelerator in the rubber industry. |
| Molecular Formula |
C15H17N3
|
|---|---|
| Molecular Weight |
239.3156
|
| Exact Mass |
239.142
|
| CAS # |
97-39-2
|
| Related CAS # |
41130-39-6 (hydrochloride)
|
| PubChem CID |
7333
|
| Appearance |
White to off-white solid powder
|
| Density |
1.1±0.1 g/cm3
|
| Boiling Point |
396.1±45.0 °C at 760 mmHg
|
| Melting Point |
176-178 °C(lit.)
|
| Flash Point |
193.3±28.7 °C
|
| Vapour Pressure |
0.0±0.9 mmHg at 25°C
|
| Index of Refraction |
1.585
|
| LogP |
3.77
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
1
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
18
|
| Complexity |
288
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
OPNUROKCUBTKLF-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C15H17N3/c1-11-7-3-5-9-13(11)17-15(16)18-14-10-6-4-8-12(14)2/h3-10H,1-2H3,(H3,16,17,18)
|
| Chemical Name |
1,2-bis(2-methylphenyl)guanidine
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~150 mg/mL (~626.78 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.45 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 25.0 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: ≥ 2.5 mg/mL (10.45 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 25.0 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 | 4.1785 mL | 20.8925 mL | 41.7851 mL | |
| 5 mM | 0.8357 mL | 4.1785 mL | 8.3570 mL | |
| 10 mM | 0.4179 mL | 2.0893 mL | 4.1785 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
