The insecticide functions as a pesticide precursor. Its lethal form, CL 303268, is produced when a mixed-function oxidase oxidizes the insecticide's N-B intermediate, uncoupling oxidative phosphate in the mitochondria. ation, which causes a disturbance in the synthesis of ATP and harm that ultimately results in cellular malfunction and the organism's mortality. Chlorfenopyr-assisted decrease of toxicity [2].

The study references a 1998 report by Kramer et al. on a one-year dietary neurotoxicity study in rats. Rats exposed to chlorfenapyr for 52 weeks developed vacuolar myelinopathy and mild myelin sheath swelling in white matter tracts. [1]

Absorption, Distribution and Excretion
The absorption rate of chlorantraniliprole after oral administration in rats is very low, with over 80% of the drug excreted in feces…
Rats were administered radioactive chlorantraniliprole via single gavage at a dose of 20 mg/kg/day, or after a 14-day pretreatment with non-radioactive chlorantraniliprole, or via single gavage at a dose of 200 mg/kg. Based on the identified metabolites, the primary depositional route of orally administered chlorantraniliprole is the excretion of the unchanged parent compound in feces. Neither of the two rings of the molecule is broken. Metabolites are primarily excreted in the urine; accumulation in tissues is minimal.

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Metabolites
Chronic acid has almost no uncoupling activity, but upon removal of the N-ethoxymethyl group via microsomal oxidation, it releases the corresponding free pyrrole (AC 303,268), a lipophilic weak acid with extremely strong uncoupling activity…AC 302,268 exhibits higher acute toxicity to vertebrates and insects than chlorantraniliprole (e.g., an acute oral LD50 of 29 mg/kg in rats). Upon injection into insects, AC 302,268 causes strong respiratory irritation almost immediately, while the parent chlorantraniliprole requires a significant delay to produce this effect. All these observations support the view that chlorantraniliprole is a prodrug that requires metabolic conversion to the active uncoupling agent AC 303,268 to exert its toxic effects.
[2-pyrrole-14C]CL 303,630 or [phenyl-(U)-14C]CL 303,630 (radiochemical purity: 99-100%, specific activities 134.7 uCi/mg and 411.4 uCi/mg, respectively) and unlabeled CL 303,630 (purity 98.8%) were suspended in 0.5% (w/w) CMC solution and administered to five male and female rats by gavage at a single dose of 20.7 or 206.7 mg/kg, and by multiple oral doses: five male and female rats were pretreated with unlabeled CL 303,630 daily. For the first 14 days after administration of [2-pyrrole-14C]CL 303,630 or [phenyl-(U)-14C]CL 303,630 at a dose of 20.5 mg/kg, regardless of the treatment regimen, 14C CL 303,630 was primarily excreted via the fecal route. 48 hours later, 70.4–91.4% and 3.9–9.7% of the administered radioactivity were detected in feces and urine, respectively. Blood and tissue concentrations were higher in females than in males, indicating a significant sex difference. Residues excreted in feces consisted primarily of the unchanged parent compound, along with small amounts of N-dealkylation, debromination, and hydroxylation oxidation products. Absorbed CL 303,630 underwent extensive metabolism in tissues and urine via N-dealkylation, debromination, cyclohydroxylation, and conjugation reactions.
AC 303,268 and its further degradation products are common metabolites of chlorantraniliprole in vertebrate studies… Following oral administration to rats, urinary metabolites include products of N-alkoxy side-chain oxidation and removal (e.g., AC 303,268) as well as cyclic hydroxylation products and their conjugates. Similar results were obtained in goats and chickens. In fish and soil, debromination is another metabolic pathway.
Organic nitriles are converted to cyanide ions in the liver by cytochrome P450 enzymes. Cyanide is rapidly absorbed and distributed throughout the body. Cyanide is primarily metabolized to thiocyanate by thiocyanate esterase or 3-mercaptopyruvate thiotransferase. Cyanide metabolites are excreted in the urine. (L96)

[1]. Chlorfenapyr-Induced Toxic Leukoencephalopathy with Radiologic Reversibility: A Case Report and Literature Review. Korean J Radiol. 2016 Mar-Apr;17(2):277-80.

[2]. Chlorfenapyr: a new insecticide with novel mode of action can control pyrethroid resistant malaria vectors. Malar J. 2011 Jan 25;10:16.

Chlorfenapyr is a pyrrole compound with the chemical name 4-bromo-1H-pyrrole-3-onitrile, in which the 1, 2, and 5 positions are substituted with ethoxymethyl, p-chlorophenyl, and trifluoromethyl, respectively. It is a precursor insecticide used to control termites and protect crops from various insect and mite pests. It is both an insecticide and an acaricide precursor. It is an organofluorine acaricide, organochlorine acaricide, organochlorine insecticide, and organofluorine insecticide, belonging to the monochlorobenzene, nitrile, pyrrole, and hemiacetal ether compounds. Functionally, it is related to tetrapyrrole compounds. Chlorfenapyr is a cyanide compound and an insecticide derived from a class of microbially synthesized compounds called halogenated pyrroles. Due to its toxicity, its use is regulated in most regions. (L596)

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Mechanism of Action
Chronic acid has almost no uncoupling activity, but after removing the N-ethoxymethyl group via microsomal oxidation, it releases the corresponding free pyrrole (AC 303,268), a lipophilic weak acid with extremely strong uncoupling activity…
Chronic acid belongs to a new class of compounds—pyrrole compounds. This compound is a precursor insecticide, meaning its biological activity depends on its activation into another chemical substance. After the N-ethoxymethyl group of chlorantraniliprole is removed by a mixed-function oxidase, compound CL 303268 is generated. CL 303268 can uncouple oxidative phosphorylation in mitochondria, leading to inhibited ATP production, cell death, and ultimately, organismal death.

C15H11BRCLF3N2O

407.62

405.969

122453-73-0

91778

Off-white to light yellow solid powder

1.5±0.1 g/cm3

443.5±45.0 °C at 760 mmHg

100.5ºC

222.0±28.7 °C

0.0±1.1 mmHg at 25°C

1.559

5.16

0

5

4

23

448

0

CCOCN1C(=C(C#N)C(=C1C(F)(F)F)Br)C2=CC=C(C=C2)Cl

CWFOCCVIPCEQCK-UHFFFAOYSA-N

InChI=1S/C15H11BrClF3N2O/c1-2-23-8-22-13(9-3-5-10(17)6-4-9)11(7-21)12(16)14(22)15(18,19)20/h3-6H,2,8H2,1H3

4-bromo-2-(4-chlorophenyl)-1-(ethoxymethyl)-5-(trifluoromethyl)pyrrole-3-carbonitrile

Chlorfenapyr AC303630 Pylon

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~250 mg/mL (~613.33 mM)

Solubility in Formulation 1: ≥ 6.25 mg/mL (15.33 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 62.5 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.

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Solubility in Formulation 2: ≥ 6.25 mg/mL (15.33 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 62.5 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)