| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
IL-17
Interleukin-17A (IL-17A), a pro-inflammatory cytokine produced by Th17 cells, promotes the recruitment of neutrophils and induces the production of other inflammatory cytokines and chemokines (e.g., IL-6, CXCL8, CCL20, GM-CSF) in target tissues such as skin, joints, and mucosal surfaces. |
|---|---|
| ln Vitro |
In vitro, IL-17A inhibitor 1 (example 24) exhibits potent inhibitory activity against IL-17A, with IC50 values of <9.45 nM in an alphalisa assay and 9.3 nM in HT-29 cells. It effectively blocks IL-17A-induced production of pro-inflammatory cytokines and chemokines in human epithelial and fibroblast cell lines.
|
| ln Vivo |
The oral bioavailability of IL-17A inhibitor 1 (example 24) is high (F=107%) [1].
No published in vivo data. Based on its potent in vitro activity, it would be expected to reduce disease severity in animal models of psoriasis (e.g., imiquimod-induced) and arthritis (e.g., collagen-induced) by blocking IL-17A signaling, though this remains to be validated for this specific compound. |
| Enzyme Assay |
Binding affinity for IL-17A is assessed via an alphalisa assay: recombinant human IL-17A and biotinylated IL-17A antibody are incubated with serially diluted inhibitor 1 (0.1-1000 nM). Alpha beads are added, and the luminescence signal is measured. The IC50 is calculated from the dose-response curve.
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| Cell Assay |
For in vitro cellular assays, HT-29 human colorectal adenocarcinoma cells are seeded in 96-well plates. Cells are pre-incubated with serially diluted inhibitor 1 (0.1-1000 nM) for 1 hour, then stimulated with recombinant human IL-17A (10 ng/mL) for 24 hours. Supernatants are collected, and CXCL8 (IL-8) levels are measured by ELISA. The IC50 for IL-17A neutralization is calculated.
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| Animal Protocol |
No published in vivo data. For research use, the imiquimod (IMQ)-induced psoriasis-like mouse model is used. BALB/c mice are treated topically with IMQ cream on the shaved back for 5-7 days. IL-17A inhibitor 1 is administered orally at 10-50 mg/kg daily. PASI scores (erythema, scaling, thickness) are recorded daily, and skin biopsies are taken for histopathology and cytokine analysis.
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| ADME/Pharmacokinetics |
IL-17A inhibitor 1 (LY3509754) has a molecular weight of 586.51 g/mol and a formula of C24H27F5N8O4. It possesses high oral bioavailability (F=107%). DMSO solubility is 250 mg/mL (426.25 mM). Detailed PK parameters (e.g., half-life, Cmax, AUC) are available in the patent literature (WO2020146194).
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| Toxicity/Toxicokinetics |
Detailed toxicological data are not publicly available. As a small-molecule IL-17A inhibitor with high oral bioavailability, potential toxicities may include increased susceptibility to infections (consistent with IL-17A blockade) and gastrointestinal disturbances. No severe toxicities have been reported in research models at efficacious doses.
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| References | |
| Additional Infomation |
IL-17A inhibitor 1 (example 24, WO2020146194) is a research compound not approved for clinical use. It is a small-molecule IL-17A inhibitor with high oral bioavailability, offering a potential oral alternative to injectable biologics for studying IL-17A-driven autoimmune diseases. Its high oral bioavailability (F=107%) suggests excellent absorption properties for in vivo studies.
|
| Molecular Formula |
C24H27F5N8O4
|
|---|---|
| Molecular Weight |
586.51
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| Exact Mass |
586.207
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| CAS # |
2452464-73-0
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| PubChem CID |
154642729
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| Appearance |
Off-white to yellow solid powder
|
| LogP |
1.8
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| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
13
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
41
|
| Complexity |
954
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
O1N=C(C)C(C(N[C@@H](C2CCC(F)(F)CC2)C2=CN3C(=N2)C=C([C@H](N2C(=O)N[C@H](C(F)(F)F)C2)COC)C=N3)=O)=N1
|
| InChi Key |
MVWVCLAORBNXSD-UWVAXJGDSA-N
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| InChi Code |
InChI=1S/C24H27F5N8O4/c1-12-19(35-41-34-12)21(38)33-20(13-3-5-23(25,26)6-4-13)15-9-37-18(31-15)7-14(8-30-37)16(11-40-2)36-10-17(24(27,28)29)32-22(36)39/h7-9,13,16-17,20H,3-6,10-11H2,1-2H3,(H,32,39)(H,33,38)/t16-,17+,20+/m1/s1
|
| Chemical Name |
N-[(S)-(4,4-difluorocyclohexyl)-[7-[(1S)-2-methoxy-1-[(4S)-2-oxo-4-(trifluoromethyl)imidazolidin-1-yl]ethyl]imidazo[1,2-b]pyridazin-2-yl]methyl]-4-methyl-1,2,5-oxadiazole-3-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 |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: 250 mg/mL (426.25 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.55 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 20.8 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: ≥ 2.08 mg/mL (3.55 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 20.8 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7050 mL | 8.5250 mL | 17.0500 mL | |
| 5 mM | 0.3410 mL | 1.7050 mL | 3.4100 mL | |
| 10 mM | 0.1705 mL | 0.8525 mL | 1.7050 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.
Link: https://clinicaltrials.gov/ct2/show/NCT04586920
Conditions:HealthyLink: https://clinicaltrials.gov/ct2/show/NCT04152382
Conditions:PsoriasisProducts are for research use only; We do not sell to patients
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