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].

Absorption, Distribution and Excretion
An oral dose of chlorfenapyr was poorly absorbed in rats and over 80% was eliminated in the feces ...
Radioactive chlorfenapyr was administered to rats by oral gavage at dose levels of 20 mg/kg/day as a single dose or following a 14-day pre-treatment with non-radioactive chlorfenapyr, or at 200 mg/kg as a single dose. Based on the metabolites identified, the major deposition route of orally administered chlorfenapyr is fecal excretion of unaltered parent compound. The two rings of the molecule are not cleaved. Metabolites are excreted primarily in urine; accumulation in tissues is minimal.

---

Metabolism / Metabolites
Chlorfenapyr shows virtually no uncoupling activity but removal of the N-ethoxymethyl group through microsomal oxidation releases the corresponding free pyrrole (AC 303,268) which is a lipophilic weak acid with very strong uncoupling activity ... AC 302,268 has an acute toxicity higher than that of chlorfenapyr in both vertebrates and insects (eg, the acute oral LD50 for the rat is 29 mg/kg). Upon injection into insects it cause an almost immediate and massive stimulation of respiration whereas the parent chlorfenapyr does so only after a significant delay. All these observations support the idea that chlorfenapyr is a proinsecticide and requires metabolic conversion to the active uncoupler, AC 303,268, before it exert a toxic action.
[2-Pyrrole-14C]CL 303,630 or [Phenyl-(U)-14C]CL 303,630 (radiochemical,purity: 99-100%, S.A. 134.7 uCi/mg and 411.4 uCi/mg, respectively) and nonlabeled CL 303,630 (...98.8% purity) were suspended in 0.5% (w/w) CMC solution and administered via gavage to 5 rats/sex as single doses of 20.7 or 206.7 mg/kg and as multiple oral doses: pretreat 5 rats/sex daily with nonlabeled CL 303,630 for 14 days prior to pulsing with 20.5 mg/kg [2-Pyrrole-14C]CL 303,630 or [Phenyl-(U)-14C]CL 303,630. Regardless of treatment regimen, 14C CL 303,630 was eliminated mainly by the fecal route. By 48 hours, 70.4-91.4% and 3.9-9.7% of the administered radioactivity was detected in feces and urine, respectively. Blood and tissue concentrations were higher in females than in males indicating that there are substantial sex-related differences. The excreted fecal residue was mainly unchanged parent compound plus minor N-dealkylated, debrominated, and hydroxylated oxidation products. Absorbed CL 303,630 was extensively metabolized in tissues and urine by N-dealkylation, debromination, ring hydroxylation, and conjugation.
AC 303,268, and its further degradation products, is a common metabolites of chlorfenapyr found in studies with vertebrates ... Urinary metabolites /from an oral dose admin in rats/ included products of N-alkoxy side chain oxidation and removal (eg, AC 303,268) and ring hydroxylation products and their conjugates. Similar results were obtained with goats and hens. In fish and soil, debromination is observed as an additional metabolic route.
Organic nitriles are converted into cyanide ions through the action of cytochrome P450 enzymes in the liver. Cyanide is rapidly absorbed and distributed throughout the body. Cyanide is mainly metabolized into thiocyanate by either rhodanese or 3-mercaptopyruvate sulfur transferase. 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 member of the class of pyrroles that is 4-bromo-1H-pyrrole-3-carbonitrile which is substituted at positions 1, 2 and 5 by ethoxymethyl, p-chlorophenyl and trifluoromethyl groups, respectively. A proinsecticide used for termite control and crop protection against several insects and mite pests. It has a role as a proinsecticide and a proacaricide. It is an organofluorine acaricide, an organochlorine acaricide, an organochlorine insecticide, an organofluorine insecticide, a member of monochlorobenzenes, a nitrile, a member of pyrroles and a hemiaminal ether. It is functionally related to a tralopyril.
Chlorfenapyr is a chemical compound of cyanide and a pesticide derived from a class of microbially produced compounds known as halogenated pyrroles. Its use is regulated in most areas due to its toxicity. (L596)

---

Mechanism of Action
Chlorfenapyr shows virtually no uncoupling activity but removal of the N-ethoxymethyl group through microsomal oxidation releases the corresponding free pyrrole (AC 303,268) which is a lipophilic weak acid with very strong uncoupling activity ...
Chlorfenapyr is a member of a new class of chemicals- the pyrroles. The compound is a pro-insecticide, i.e. the biological activity depends on its activation to another chemical. Oxidative removal of the N-ethoxymethyl group of chlorfenapyr by mixed function oxidases forms the compound CL 303268. CL 303268 uncouples oxidative phosphorylation at the mitochondria, resulting in disruption of production of ATP, cellular death, and ultimately organism mortality.

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.

---

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.

---

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