Metabolism / Metabolites
This study investigated the metabolism of DPX-JW062 and DPX-MP062 in rats after oral administration. Most of the drug was excreted within 96 hours. The drug underwent extensive metabolism, producing various minor metabolites. Urinary metabolites were cleavage products (indanate or trifluoromethoxybenzene ring products), while fecal metabolites retained both structures. Major metabolic reactions included hydroxylation of the indanate ring, hydrolysis of the carboxymethyl group on the amino nitrogen atom, and ring-opening of the oxadiazine ring, all of which generated cleavage products. (A15205)

Toxicity Summary
It is believed that the aromatic metabolites of indoxacarb can be bioconverted into an active intermediate, subsequently producing methemoglobin (A15207). The mechanism by which indoxacarb causes kidney damage and metabolic acidosis in humans is unclear. Studies have shown that acute kidney injury (A15207) is caused by circulatory shock induced by indoxacarb (A15206). Methemoglobinemia (A15206) may induce rhabdomyolysis.

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Toxicity Data
LC50 (Rat) = 4200 mg/m3Non-human Toxicity Values
LD50 Male rats, oral administration 1732 mg/kg/DPX-MP062, (S) and (R) isomers 3:1 mixture/
LD50 Female rats, oral administration 268 mg/kg/DPX-MP062, (S) and (R) isomers 3:1 mixture/
LD50 Rabbits, dermal >5000 mg/kg/DPX-MP062, (S) and (R) isomers 3:1 mixture/

[1]. Indoxacarb effects on non-target predator, Podisus distinctus (Hemiptera: Pentatomidae)

Indoxacarb is an organochlorine insecticide belonging to the methyl ester class. It is a voltage-gated sodium channel blocker. Indoxacarb is an oxadiazine insecticide developed by DuPont, effective against lepidopteran larvae. Its trade names include Indoxacarb technical, Steward insecticide, and Avaunt insecticide. It is also the active ingredient in DuPont's commercial insecticide lines Advion and Arilon. Indications: For the treatment and prevention of flea infestations. Suitable for dogs and cats: For the treatment and prevention of flea infestations. This veterinary drug can be used as part of a treatment regimen for flea allergic dermatitis. Fleas in the pet's environment are killed upon contact with a pet treated with Activyl. Mechanism of Action: ...Indoxacarb inhibits sodium channels and certain subtypes of nicotine receptors. This study used whole-cell patch-clamp technique to investigate the effects of the diazinon insecticide indoxacarb and its N-decarboxymethoxy metabolite (DCJW) on tetrodotoxin-resistant (TTX-R) voltage-gated sodium channels in rat dorsal ganglion neurons. Both indoxacarb and DCJW inhibited the peak amplitude of action potentials, with DCJW showing faster onset and higher potency than indoxacarb. In voltage-clamp experiments, both indoxacarb and DCJW inhibited TTX-R sodium currents in a time-dependent manner, but did not reach steady-state inhibition levels. After 25 minutes of perfusion, the IC50 values of indoxacarb and DCJW for TTX-R sodium currents were estimated to be 10.7 μM and 0.8 μM, respectively. The potency of DCJW in blocking TTX-R sodium currents was approximately 10 times that of indoxacarb. Although the inhibitory effect of indoxacarb was partially reversible after elution with a drug-free external solution, no recovery of sodium current was observed in neurons treated with DCJW, even after prolonged elution. In the current-voltage relationship, indoxacarb and DCJW exhibited similar blocking effects on sodium current across the entire membrane potential range. Neither 10 μM indoxacarb nor DCJW shifted the sodium conductance-voltage curve along the voltage axis. Conversely, both indoxacarb and DCJW shifted the steady-state inactivation curve toward hyperpolarization. Based on these results, it can be concluded that indoxacarb and DCJW effectively block the TTX-R sodium channel in rat dorsal root ganglion (DRG) neurons and cause a hyperpolarization shift in the steady-state inactivation curve, indicating that these insecticides preferentially bind to the inactivated state of sodium channels. The subtle structural differences between indoxacarb and DCJW lead to significant differences in their sodium channel blocking efficacy and reversibility after elution.

C22H17N3O7F3CL

527.83448

527.07

173584-44-6

107720

White powder

1.5±0.1 g/cm3

571.4±60.0 °C at 760 mmHg

88.1ºC

299.3±32.9 °C

0.0±1.6 mmHg at 25°C

1.602

2.77

0

11

5

36

912

1

COC(=O)[C@@]12CC3=CC(=CC=C3C2=NN(CO1)C(=O)N(C4=CC=C(C=C4)OC(F)(F)F)C(=O)OC)Cl

VBCVPMMZEGZULK-NRFANRHFSA-N

InChI=1S/C22H17ClF3N3O7/c1-33-18(30)21-10-12-9-13(23)3-8-16(12)17(21)27-28(11-35-21)19(31)29(20(32)34-2)14-4-6-15(7-5-14)36-22(24,25)26/h3-9H,10-11H2,1-2H3/t21-/m0/s1

methyl (4aS)-7-chloro-2-[methoxycarbonyl-[4-(trifluoromethoxy)phenyl]carbamoyl]-3,5-dihydroindeno[1,2-e][1,3,4]oxadiazine-4a-carboxylate

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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