| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
IL-17A
IL-17A (interleukin-17A). IL-17A antagonist 3 is a direct inhibitor of IL-17A, blocking its binding to the IL-17 receptor complex (IL-17RA/IL-17RC). This inhibition prevents the activation of downstream NF-kappaB and MAPK signaling pathways, thereby reducing the production of pro-inflammatory cytokines and chemokines. |
|---|---|
| ln Vitro |
In vitro, IL-17A antagonist 3 potently inhibits IL-17A-induced activation of downstream signaling pathways. It blocks IL-17A-stimulated production of pro-inflammatory cytokines and chemokines (e.g., IL-6, CXCL8, CCL20) in cell lines such as human primary dermal fibroblasts, keratinocytes, or synoviocytes. The IC50 is typically in the low nanomolar to micromolar range, depending on the assay.
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| ln Vivo |
In preclinical animal models of psoriasis and arthritis (e.g., imiquimod-induced psoriasis-like dermatitis in mice or collagen-induced arthritis (CIA) in rats), IL-17A antagonist 3 reduces clinical disease severity. It ameliorates skin inflammation (erythema, scaling, thickening) and joint swelling, correlating with decreased histopathological scores and reduced levels of IL-17-driven inflammatory markers in affected tissues.
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| Enzyme Assay |
To assess binding, a direct binding assay (e.g., surface plasmon resonance or ELISA) is used. Recombinant human IL-17A protein is immobilized on a sensor chip or microplate, and serially diluted antagonist 3 (e.g., 0.1-1000 nM) is flowed over or added. The equilibrium dissociation constant (KD) is calculated from the binding sensorgram or from the ELISA signal measured with a labeled detection reagent (e.g., anti-IL-17A antibody).
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| Cell Assay |
For in vitro cellular assays, human foreskin fibroblasts (HFF-1) or HaCaT keratinocytes are used. Cells are seeded in 96-well plates and pre-incubated with serially diluted antagonist 3 (e.g., 0.01-100 uM) for 1 hour, then stimulated with recombinant human IL-17A (e.g., 10 ng/mL) for 24 hours. Supernatants are collected, and cytokine levels (IL-6, CXCL8, CCL20) are measured by ELISA. Cell viability is assessed using an MTT or CellTiter-Glo assay to rule out cytotoxicity.
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| Animal Protocol |
To evaluate in vivo efficacy, the imiquimod (IMQ)-induced psoriasis-like mouse model is used. BALB/c mice are treated topically with IMQ cream (5%, 62.5 mg) on the shaved back for 5-7 consecutive days to induce skin inflammation. IL-17A antagonist 3 is administered orally (e.g., 10-100 mg/kg) once or twice daily starting on day 0. Psoriasis Area and Severity Index (PASI) scores (erythema, scaling, thickness) are recorded daily. On the final day, skin biopsies are taken for histopathological analysis (H&E staining) and for qPCR or ELISA measurement of inflammatory cytokines (IL-6, TNF-alpha, IL-22).
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| ADME/Pharmacokinetics |
IL-17A antagonist 3 has a molecular weight of 613.11 g/mol. It is a small molecule with suitable drug-like properties for oral administration. Detailed in vivo PK parameters (e.g., half-life, Cmax, oral bioavailability) are available in the patent literature (WO 2020127685).
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| Toxicity/Toxicokinetics |
Information on toxicological profiles is limited to data reported in the patent literature. In general, preclinical safety studies indicate that IL-17A antagonist 3 is well-tolerated at efficacious dose levels, with no severe adverse effects observed. As a small molecule, it may be associated with off-target liabilities that require further optimization.
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| References | |
| Additional Infomation |
IL-17A antagonist 3 is a research chemical that has not been approved for clinical use. It is extracted from patent WO 2020127685 and is provided for laboratory research purposes only. This compound is a direct small-molecule inhibitor of IL-17A, offering a potential oral alternative to injectable biologics for studying IL-17-driven autoimmune diseases.
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| Molecular Formula |
C33H33CLN6O4
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|---|---|
| Molecular Weight |
613.11
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| Exact Mass |
612.225
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| CAS # |
2230780-65-9
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| PubChem CID |
121499150
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| Appearance |
White to off-white solid powder
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| LogP |
3.9
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
44
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| Complexity |
1020
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C12CCC(=O)N[C@@H](C(=O)NC)CC3=CC=C(C=C3)NC(=O)[C@@H](NC(C3N(C)N=CC=3)=O)CC3=C(C=CC(=C3)C(=CC=C1)C=2)Cl
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| InChi Key |
CEFRORFLEYHRHI-IZLXSDGUSA-N
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| InChi Code |
InChI=1S/C33H33ClN6O4/c1-35-31(42)27-17-21-6-10-25(11-7-21)37-32(43)28(39-33(44)29-14-15-36-40(29)2)19-24-18-23(9-12-26(24)34)22-5-3-4-20(16-22)8-13-30(41)38-27/h3-7,9-12,14-16,18,27-28H,8,13,17,19H2,1-2H3,(H,35,42)(H,37,43)(H,38,41)(H,39,44)/t27-,28+/m1/s1
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| Chemical Name |
(4S,20R)-7-chloro-N-methyl-4-[(2-methylpyrazole-3-carbonyl)amino]-3,18-dioxo-2,19-diazatetracyclo[20.2.2.16,10.111,15]octacosa-1(25),6,8,10(28),11,13,15(27),22(26),23-nonaene-20-carboxamide
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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: 6.67 mg/mL (10.88 mM)
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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 | 1.6310 mL | 8.1551 mL | 16.3103 mL | |
| 5 mM | 0.3262 mL | 1.6310 mL | 3.2621 mL | |
| 10 mM | 0.1631 mL | 0.8155 mL | 1.6310 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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