| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
Chlorpyrifos-oxon targets acetylcholinesterase (AChE), acting as a potent inhibitor. It is a phosphorylating agent that covalently modifies the active site serine residue of AChE, leading to irreversible inhibition. This mechanism is responsible for its neurotoxic effects.
|
|---|---|
| ln Vitro |
Protein aggregation occurs when 1.5 mM chlorpyrifos-oxon (CPO) is applied to tubulin. Nonetheless, cross-linked trimers between chlorpyrifos and oxon are visible even at 1.5 μM. Chlorpyrifos-oxon facilitates tubulin monomers' isopeptide bond cross-linking to form multimers[2]. Neurite outgrowth was hindered in PC12 cells cultured for 24 hours when exposed to chlorpyrifos at a dosage 10-fold lower than that which inhibits AChE activity (3.0 μM), but neurite outgrowth is inhibited at 1.0 nM by chlorpyrifos-oxon[3].
In cell-free enzyme assays, Chlorpyrifos-oxon is a potent inhibitor of AChE. It acts as a phosphorylating agent, forming a covalent bond with the enzyme. Its inhibitory potency is significantly greater than that of the parent compound chlorpyrifos. These assays are used to study the mechanism of organophosphate poisoning. In cellular assays, Chlorpyrifos-oxon inhibits AChE activity in neuronal cells, leading to an accumulation of acetylcholine. This disrupts cholinergic signaling and can lead to neurotoxicity. It is used in toxicology research to study the cellular effects of organophosphate exposure. |
| ln Vivo |
Human liver microsomes quickly detoxify chlorpyrifos-oxon (CPO) by glutathione-S-transferase and CYP-dependent deethylation and dearylation. Furthermore, Chlorpyrifos-oxon may be quickly degraded or scavenged in the liver by interactions with A-esterases like paraoxonase 1 (PON 1) or B-esterases such carboxylesterase and butyrylcholinesterase (BChE)[1]. Following treatment with Chlorpyrifos-oxon (3 mg/kg, ip; once); wild-type mice, the microtubule dimensions of the treated mice resemble those of the control mice by almost 60%. Mice exposed to chlorpyrifos-oxon had microtubules with aberrant structures and covalently changed amino acids, which may indicate a disruption in microtubule function[4].
In vivo, Chlorpyrifos-oxon is the proximate toxin responsible for the toxic effects of chlorpyrifos. It is formed in the body through oxidative metabolism of chlorpyrifos. It causes neurotoxicity by inhibiting AChE in the nervous system. It is used in toxicology research to study organophosphate poisoning. |
| Enzyme Assay |
Cell-free enzyme inhibition assays for Chlorpyrifos-oxon are performed using purified AChE enzyme. The enzyme is incubated with varying concentrations of the compound and a chromogenic substrate. The rate of substrate hydrolysis is measured spectrophotometrically, and the IC50 value is determined from the inhibition curve.
|
| Cell Assay |
Cellular assays for Chlorpyrifos-oxon are conducted using neuronal cell lines. Cells are treated with the compound, and AChE activity is measured. Markers of cholinergic dysfunction, such as acetylcholine levels, are assessed. Neurotoxicity is evaluated by measuring cell viability and oxidative stress.
|
| Animal Protocol |
In vivo studies on Chlorpyrifos-oxon are conducted in animal models to study organophosphate toxicity. The compound is administered, and its effects on AChE activity, cholinergic signaling, and behavior are assessed. These studies help to understand the mechanisms of organophosphate poisoning and develop countermeasures.
|
| ADME/Pharmacokinetics |
Metabolism / Metabolites
The known human metabolites of chlorpyrifos oxyphosphine include diethyl thiophosphate and 3,5,6-trichloro-2-pyridinol. Chlorpyrifos oxyphosphine is a known human metabolite of chlorpyrifos. The metabolism of organophosphates mainly occurs through oxidation, esterase hydrolysis, and reactions with glutathione. Demethylation and glucuronidation may also occur. Oxidation of organophosphate pesticides can produce moderately toxic products. Generally, thiophosphates themselves are not directly toxic and require oxidative metabolism to be converted into proximal toxins. Products produced by glutathione transferase reactions are generally less toxic. Paraoxygenase (PON1) is a key enzyme in organophosphate metabolism. PON1 can inactivate some organophosphates through hydrolysis. PON1 can hydrolyze active metabolites in many organophosphate insecticides and nerve agents (such as soman, sarin, and VX). The presence of PON1 polymorphism leads to differences in the enzyme activity level and catalytic efficiency of this esterase, suggesting that different individuals may be more susceptible to the toxicity of organophosphate toxins. Chlorpyrifos-oxon is a metabolite and is not administered as a therapeutic agent. Its pharmacokinetics are related to the metabolism of chlorpyrifos. It is formed in the liver and other tissues and rapidly binds to AChE. |
| Toxicity/Toxicokinetics |
Toxicity Summary
Chlorpyrifos is a cholinesterase, or acetylcholinesterase (AChE) inhibitor. Cholinesterase inhibitors (or "anticholinesterases") inhibit the activity of acetylcholinesterase. Because acetylcholinesterase has important physiological functions, chemicals that interfere with its activity are potent neurotoxins; even low doses can cause excessive salivation and lacrimation, followed by muscle spasms and ultimately death. Nerve gases and substances used in many pesticides have been shown to work by binding to serine residues at the active site of acetylcholinesterase, thereby completely inhibiting the enzyme's activity. Acetylcholinesterase breaks down the neurotransmitter acetylcholine, which is released at the neuromuscular junction, causing muscle or organ relaxation. Inhibition of acetylcholinesterase results in the accumulation and sustained action of acetylcholine, leading to continuous nerve impulse transmission and unstoppable muscle contractions. The most common acetylcholinesterase inhibitors are phosphorus-containing compounds designed to bind to the enzyme's active site. Its structural requirements include a phosphorus atom with two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen atom. Chlorpyrifos-oxon is highly toxic due to its potent AChE inhibition. It can cause acute toxicity characterized by cholinergic crisis, including salivation, lacrimation, urination, defecation, gastrointestinal distress, and muscle fasciculations. It is classified as a hazardous substance. |
| References |
|
| Additional Infomation |
By comparing environmental concentrations of chlorpyrifos and oxyphosphorus with toxic concentration data, the acute toxicity risk of chlorpyrifos to soil microorganisms can be assessed. In animals, chlorpyrifos is converted into chlorpyrifos oxyphosphorus, which is approximately 3000 times more toxic to the nervous system than chlorpyrifos itself.
Chlorpyrifos-oxon is a research compound used in toxicology and neurobiology to study mechanisms of organophosphate poisoning, cholinergic dysfunction, and the health risks associated with pesticide exposure. It is not approved for any therapeutic use. |
| Molecular Formula |
C9H11CL3NO4P
|
|---|---|
| Molecular Weight |
334.52
|
| Exact Mass |
332.949
|
| CAS # |
5598-15-2
|
| Related CAS # |
Chlorpyrifos-oxon-d10;1794779-85-3
|
| PubChem CID |
21804
|
| Appearance |
White to off-white <43°C powder,>53°C liquid
|
| Density |
1.461g/cm3
|
| Boiling Point |
357.8ºC at 760mmHg
|
| Flash Point |
170.2ºC
|
| Index of Refraction |
1.523
|
| LogP |
4.601
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
18
|
| Complexity |
300
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CCOP(OC1=NC(Cl)=C(Cl)C=C1Cl)(=O)OCC
|
| InChi Key |
OTMOUPHCTWPNSL-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C9H11Cl3NO4P/c1-3-15-18(14,16-4-2)17-9-7(11)5-6(10)8(12)13-9/h5H,3-4H2,1-2H3
|
| Chemical Name |
diethyl (3,5,6-trichloropyridin-2-yl) phosphate
|
| 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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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: 100 mg/mL (298.94 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.47 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 (7.47 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.47 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9894 mL | 14.9468 mL | 29.8936 mL | |
| 5 mM | 0.5979 mL | 2.9894 mL | 5.9787 mL | |
| 10 mM | 0.2989 mL | 1.4947 mL | 2.9894 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
