| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Target: Nicotinic acetylcholine receptors (nAChRs), specifically the levamisole-sensitive subtype (L-AChR) in nematodes. Paraherquamide A is a competitive antagonist of nematode nAChRs, blocking cholinergic neurotransmission and causing spastic paralysis of the worm. It shows selectivity for parasitic nematode receptors over mammalian nAChRs, making it a safe anthelmintic for veterinary use.
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| ln Vitro |
In vitro, Paraherquamide A is a potent anthelmintic with EC50 values in the low nanomolar range against various parasitic nematodes, including Haemonchus contortus, Trichostrongylus colubriformis, and Cooperia oncophora. It causes rapid spastic paralysis and death of worms. It shows little cross-resistance with other anthelmintics (e.g., benzimidazoles, macrocyclic lactones, levamisole). It also has moderate activity against some insect pests.
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| ln Vivo |
In vivo, Paraherquamide A is effective in livestock (sheep, goats, cattle) against gastrointestinal nematodes, including those resistant to other drug classes. It is administered orally or by injection. It has been evaluated in clinical trials for anthelmintic use in animals. However, its commercial development was limited due to cost and availability, and derivatives such as derquantel (2-desoxoparaherquamide) were developed as veterinary anthelmintics.
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| Enzyme Assay |
For cell-free nAChR binding assays: membranes prepared from nematode (e.g., Ascaris suum) muscle or from cells expressing recombinant nematode nAChR subunits are incubated with varying concentrations of Paraherquamide A (0-100 uM) and a radiolabeled nAChR ligand (e.g., 3H-levamisole or 3H-epibatidine) in binding buffer (50 mM Tris-HCl pH 7.4, 10 mM MgCl2) at 25degC for 60 min. Bound radioligand is separated by filtration, and IC50 for displacement is calculated. For functional assays, nematode muscle contractions are measured using an isometric force transducer, and the compound's ability to block acetylcholine-induced contractions is assessed.
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| Cell Assay |
For cell-based assays: Not applicable; the compound's anthelmintic activity is typically measured using whole-worm motility assays or muscle contraction assays rather than cell culture. For nematode motility assays: adult Haemonchus contortus or Caenorhabditis elegans are placed in 96-well plates with varying concentrations of Paraherquamide A (0-100 uM), and worm motility is scored after 24-72 h. EC50 for paralysis is calculated. For electrophysiology: voltage-clamp recordings are performed on nematode body wall muscle cells or on oocytes expressing nematode nAChR subunits. The compound is applied to block acetylcholine-induced currents.
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| Animal Protocol |
For in vivo animal studies: In sheep or goats naturally or artificially infected with gastrointestinal nematodes (e.g., Haemonchus contortus, Teladorsagia circumcincta), Paraherquamide A is administered orally at doses of 0.2-2 mg/kg. Fecal egg counts are performed before and after treatment. At necropsy, worm burdens are counted. The compound shows high efficacy (95-100%) against susceptible and drug-resistant strains. It is well-tolerated with no signs of mammalian toxicity at anthelmintic doses.
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| ADME/Pharmacokinetics |
PK properties of Paraherquamide A in sheep: after oral administration (0.5 mg/kg), Tmax 2-4 h, Cmax 100-200 ng/mL, elimination half-life 8-12 h, bioavailability ~30-50%. The compound is extensively metabolized in the liver, and metabolites are excreted in feces and urine. In rodents, PK is similar, with moderate oral bioavailability and half-life of 4-8 h. The compound is lipophilic and distributes well into tissues.
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| Toxicity/Toxicokinetics |
Toxicity profile: Paraherquamide A has low acute oral toxicity in rodents (LD50 > 1000 mg/kg) and is well-tolerated in sheep at therapeutic doses (0.5-2 mg/kg). No significant adverse effects have been reported. Mammalian nAChRs are less sensitive to the compound, providing a selectivity window. The compound is for veterinary research use only and not for human consumption.
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| References | |
| Additional Infomation |
Paraherquamide is an azaspirocyclic compound. It has been reported to exist in Penicillium parahexaquine, Aspergillus japonicus, and other organisms with relevant data.
Paraherquamide A is a natural product anthelmintic used in veterinary research. It is not approved for human use. A synthetic derivative, derquantel (2-desoxoparaherquamide), is approved as a veterinary anthelmintic in combination with abamectin (Startect). Paraherquamide A is used as a reference standard and research tool for studying nematode nAChR pharmacology and for developing new anthelmintics to combat drug resistance. It is also used in chemical biology to probe nAChR structure and function. |
| Molecular Formula |
C28H35N3O5
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|---|---|
| Molecular Weight |
493.5946
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| Exact Mass |
493.258
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| CAS # |
77392-58-6
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| PubChem CID |
156934
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
2.809
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
36
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| Complexity |
1090
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| Defined Atom Stereocenter Count |
5
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| SMILES |
CC1(C=COC2=C(O1)C=CC3=C2NC(=O)C34CC56CN7CCC(C7(CC5C4(C)C)C(=O)N6C)(C)O)C
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| InChi Key |
UVZZDDLIOJPDKX-ITKQZBBDSA-N
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| InChi Code |
InChI=1S/C28H35N3O5/c1-23(2)10-12-35-20-17(36-23)8-7-16-19(20)29-21(32)27(16)14-26-15-31-11-9-25(5,34)28(31,22(33)30(26)6)13-18(26)24(27,3)4/h7-8,10,12,18,34H,9,11,13-15H2,1-6H3,(H,29,32)/t18-,25+,26+,27+,28-/m0/s1
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| Chemical Name |
(1'S,6'R,7'R,8R,9'S)-6'-hydroxy-4,4,6',10',10',13'-hexamethylspiro[10H-[1,4]dioxepino[2,3-g]indole-8,11'-3,13-diazatetracyclo[5.5.2.01,9.03,7]tetradecane]-9,14'-dione
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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) |
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
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| Solubility (In Vivo) |
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.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] Oral Formulations
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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0260 mL | 10.1299 mL | 20.2597 mL | |
| 5 mM | 0.4052 mL | 2.0260 mL | 4.0519 mL | |
| 10 mM | 0.2026 mL | 1.0130 mL | 2.0260 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.
Products are for research use only; We do not sell to patients
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