Chlorpyrifos-oxon

• CAT Number: R054905
• CAS Number: 5598-15-2
• Molecular Formula: C9H11Cl3NO4P
• Molecular Weight: 334.52
• Purity: ≥95%
• Synonyms: diethyl (3,5,6-trichloropyridin-2-yl) phosphate
• InChI: 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
• InChIKey: OTMOUPHCTWPNSL-UHFFFAOYSA-N
• SMILES: CCOP(=O)(OCC)OC1=NC(=C(C=C1Cl)Cl)Cl

Chlorpyrifos-oxon, an active metabolite of Chlorpyrifos, is a potent phosphorylating agent that potently inhibits AChE. Chlorpyrifos-oxon can induce cross-linking between subunits of tubulin and disrupt microtubule function[1][2][3][4].
Treatment of tubulin with 1.5 mM Chlorpyrifos-oxon (CPO) leads to protein aggregation. However, even at 1.5 μM Chlorpyrifos-oxon cross-linked trimers are apparent. Chlorpyrifos-oxon promotes isopeptide bond cross-linking of tubulin monomers to make multimers[2].
In PC12 cells in culture, 24 hours of exposure to Chlorpyrifos at a concentration 10-fold below the concentration that inhibits AChE activity (3.0 μM) impaired neurite outgrowth while Chlorpyrifos-oxon inhibits neurite outgrowth at 1.0 nM[3].
Chlorpyrifos-oxon (CPO) is rapidly detoxified by human liver microsomes via CYP-dependent deethylation and dearylation, and by glutathione-S-transferase. In addition, reactions with A-esterases such as paraoxonase 1 (PON 1) or B-esterases such as carboxylesterase and butyrylcholinesterase (BChE) in the liver may rapidly degrade or scavenge Chlorpyrifos-oxon[1].
Chlorpyrifos-oxon (3 mg/kg, ip; once; wild-type mice) treatment shows the dimensions of microtubules from Chlorpyrifos-oxon-treated mice are about 60% of those from control mice. The microtubules from mice exposed to Chlorpyrifos-oxon have covalently modified amino acids and abnormal structure, suggesting disruption of microtubule function[4].

Reference

[1]. Florian Eyer, et al. Extreme variability in the formation of chlorpyrifos oxon (CPO) in patients poisoned by chlorpyrifos (CPF). Biochem Pharmacol. 2009 Sep 1;78(5):531-7.
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[2]. Lawrence M Schopfer, et al. Chlorpyrifos oxon promotes tubulin aggregation via isopeptide cross-linking between diethoxyphospho-Lys and Glu or Asp: Implications for neurotoxicity. J Biol Chem. 2018 Aug 31;293(35):13566-13577.
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[3]. Jie Gao, et al. Chlorpyrifos and chlorpyrifos oxon impair the transport of membrane bound organelles in rat cortical axons. Neurotoxicology. 2017 Sep;62:111-123.
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[4]. Wei Jiang, et al. Mice treated with chlorpyrifos or chlorpyrifos oxon have organophosphorylated tubulin in the brain and disrupted microtubule structures, suggesting a role for tubulin in neurotoxicity associated with exposure to organophosphorus agents.
 [Content Brief]