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| Targets |
Monepantel targets the nematode-specific acetylcholine receptor subunit, specifically the MPTL-1 (Monepantel-1) receptor. This receptor is a unique ligand-gated ion channel found only in nematodes. By binding to the MPTL-1 receptor, monepantel causes spastic paralysis of the worm, leading to its expulsion from the host. The compound's selective toxicity is based on the absence of this receptor in mammals, contributing to its safety profile.
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| ln Vitro |
The presence of monepantel (25 μM) causes acidic vacuoles to accumulate. Liver cancer lines are very sensitive to Monepantel, with IC50 values of 7.2±0.2 μM (OVCAR-3) and 10.5±0.4 μM (A2780). Monepantel (0, 10 and 25 μM) stimulates autophagosome production in these Manhattan lines. Monepantel (0, 10, and 25 μM) revealed significantly lower levels of punctate staining, indicating suppression of Ser2448 phosphorylated mTOR. Monepantel also reduces the phosphorylated expression of Raptor at Ser792, a member of the mTORC1 coMonepantelex [2]. Monepantel (250 μg/mL) resulted in higher acetone expression of multiple ABC transporter genes in both worm isolates. Larvae exposed to 250 μg/mL Monepantel showed increased efflux of rhodamine-123, and some larval populations showed the ability to tolerate higher concentrations of IVM in migration assays [3].
In vitro, monepantel demonstrates potent anthelmintic activity against various nematode species, including Haemonchus contortus, Teladorsagia circumcincta, and Trichostrongylus colubriformis. The compound's activity is assessed using larval development assays, motility assays, and in vitro culture of adult worms. Monepantel is effective against both susceptible and drug-resistant nematode strains, including those resistant to benzimidazoles, levamisole, and macrocyclic lactones. |
| ln Vivo |
In sheep, monepantel (10 μM) dramatically raises CYP3A24 mRNA and all CYP-related activity [4].
In vivo, monepantel is highly effective against gastrointestinal nematodes in sheep and cattle. The compound is administered orally and achieves high efficacy against adult and larval stages of important nematode species. In clinical trials, monepantel demonstrated >95% efficacy against major nematode parasites in sheep, including drug-resistant strains. The compound is used for the treatment and control of nematode infections in livestock. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for monepantel measure its affinity for the nematode MPTL-1 receptor. Receptor binding studies use membrane preparations from nematodes expressing the MPTL-1 receptor, incubated with radiolabeled monepantel or a competitive ligand. The binding affinity (Ki) is calculated from displacement curves. Functional assays measure receptor activation using calcium flux or electrophysiological techniques in cells expressing the recombinant receptor.
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| Cell Assay |
In vitro cell-based assays for monepantel use nematode cultures, including larval stages and adult worms. The compound's effects on worm motility, feeding, and viability are assessed. Larval development assays involve incubating nematode eggs or L1 larvae with serial dilutions of monepantel and assessing development to L3 stage. Motility assays use video tracking or visual scoring to measure the effect of the compound on worm movement. EC50 values are calculated from dose-response curves.
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| Animal Protocol |
In vivo animal models for monepantel use sheep, cattle, or goats infected with nematode parasites. Animals are treated with monepantel at various doses, and efficacy is evaluated by fecal egg count reduction tests (FECRT) or by counting worm burdens at necropsy. Dose-response studies establish the effective dose for 50% and 90% reduction in fecal egg counts (ED50 and ED90). Pharmacodynamic studies assess the duration of action and efficacy against different parasite stages.
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| ADME/Pharmacokinetics |
Monepantel is orally administered and is absorbed from the gastrointestinal tract. The compound undergoes metabolism in the liver to its active sulfone metabolite, which is primarily responsible for the anthelmintic activity. The parent compound and its metabolite are distributed to tissues and reach therapeutic concentrations in the gastrointestinal tract where the parasites reside. The elimination half-life in sheep is approximately 4-6 days. The compound is excreted mainly via feces and urine.
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| Toxicity/Toxicokinetics |
Monepantel has a favorable safety profile in target animals. The selective toxicity is based on the absence of the MPTL-1 receptor in mammals. Adverse effects are minimal at therapeutic doses. Overdose may cause transient signs of gastrointestinal discomfort. The compound is well-tolerated in sheep and cattle, including pregnant and lactating animals. Withdrawal periods are established for meat and milk to ensure food safety.
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| References |
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| Additional Infomation |
Monepant is a secondary amide formed by the condensation of the carboxyl group of p-[(trifluoromethyl)thio]benzoic acid with the amino group of (2S)-2-amino-3-hydroxy-2-methylpropionitrile, wherein the hydroxyl group is converted to the corresponding 5-cyano-2-(trifluoromethyl)phenyl ether. It is a broad-spectrum nematicide used to control gastrointestinal nematodes in sheep and goats. It is both an anthelmintic and a nematicide. It is a nitrile compound, an aryl thioether compound, an aromatic ether compound, a (trifluoromethyl)benzene compound, and a secondary amide compound.
Drug Indications Zolvix oral solution is a broad-spectrum anthelmintic used to treat and control gastrointestinal nematode infections and related diseases in sheep (including lambs, yearlings, rams, and ewes). Its activity spectrum includes fourth-instar larvae and adults of the following nematodes: Haemaphys contortus; Tyrodactylus annularus; Tyrodactylus trigeminatus; Tyrodactylus dauricus; Trichodina axialii; Trichodina coli; Trichodina viride; Cooperia spp.; Cooperia spp.; Babylonia spp.; Nematoda; Nematoda barbae; Nematoda spp.; Nematoda sheareri; Nematoda spp.; Nematoda venosa. Includes inhibited larvae. This veterinary drug is effective against the above-mentioned parasitic strains resistant to (proto)benzimidazoles, levamisole, morantral, and macrolides, as well as Haemaphys contortus strains resistant to salicylanilides. Monepantel is approved and marketed for the treatment of gastrointestinal nematode infections in sheep under the brand name Zolvix. It is also approved for use in cattle in some countries. The compound's unique mechanism of action—targeting the nematode-specific MPTL-1 receptor—provides an important tool for managing drug-resistant nematode populations. It is used as part of integrated parasite management programs in livestock production. |
| Molecular Formula |
C20H13F6N3O2S
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|---|---|
| Molecular Weight |
473.3934
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| Exact Mass |
473.063
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| CAS # |
887148-69-8
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| Related CAS # |
(Rac)-Monepantel-d5;2747918-33-6;(Rac)-Monepantel sulfone-d5;2747918-68-7;(R)-Monepantel
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| PubChem CID |
44449087
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| Appearance |
White to off-white solid powder
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| LogP |
5.67
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
32
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| Complexity |
763
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C[C@@](COC1=C(C=CC(=C1)C#N)C(F)(F)F)(C#N)NC(=O)C2=CC=C(C=C2)SC(F)(F)F
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| InChi Key |
WTERNLDOAPYGJD-SFHVURJKSA-N
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| InChi Code |
InChI=1S/C20H13F6N3O2S/c1-18(10-28,11-31-16-8-12(9-27)2-7-15(16)19(21,22)23)29-17(30)13-3-5-14(6-4-13)32-20(24,25)26/h2-8H,11H2,1H3,(H,29,30)/t18-/m0/s1
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| Chemical Name |
N-[(2S)-2-cyano-1-[5-cyano-2-(trifluoromethyl)phenoxy]propan-2-yl]-4-(trifluoromethylsulfanyl)benzamide
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| Synonyms |
AAD-1566; AAD1566; AAD 1566
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (~211.24 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.28 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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 (5.28 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1124 mL | 10.5621 mL | 21.1242 mL | |
| 5 mM | 0.4225 mL | 2.1124 mL | 4.2248 mL | |
| 10 mM | 0.2112 mL | 1.0562 mL | 2.1124 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.
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