| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
| Targets |
Interleukin-1 receptor (IL-1R) (IC50 = 1.2 μM for inhibiting IL-1-mediated NF-κB activation) [1]
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| ln Vitro |
In EL4 thymoma cells and freshly separated murine lymphocytes, TLR1 suppresses IL-1β-induced activation of mitogen-activated protein kinase p38 in a concentration-dependent manner [1].
IL-1R-mediated signaling inhibition: IL-1R antagonist potently inhibits IL-1-induced NF-κB activation in HEK293 cells stably expressing IL-1R and a NF-κB luciferase reporter, with an IC50 of 1.2 μM. It does not affect TNF-α or LPS-mediated NF-κB activation, demonstrating selectivity for IL-1R signaling [1] - Cytokine secretion suppression: In human peripheral blood mononuclear cells (PBMCs), the compound inhibits IL-1-induced production of pro-inflammatory cytokines IL-6 and IL-8. At 10 μM, IL-6 secretion is reduced by 78% and IL-8 secretion by 82% compared to the IL-1-stimulated control [1] - TIR domain interaction mimicry: The compound binds to the TIR domain of IL-1R-associated kinase (IRAK), blocking the interaction between IRAK and MyD88 (an adaptor protein in IL-1R signaling). This abrogates downstream MAPK and NF-κB pathway activation [1] |
| ln Vivo |
The mouse MyD88 and IL-1RI interaction in the TIR domain is disrupted by TLR1. When IL-1β (200 mg/kg) is injected intraperitoneally, TLR1 can greatly reduce the fever that results [1].
Acute inflammation inhibition: C57BL/6 mice were pretreated with IL-1R antagonist (10 mg/kg, i.p.) 1 hour before intraperitoneal (i.p.) injection of IL-1β (1 μg/mouse). Serum IL-6 levels measured 2 hours post-IL-1β injection were reduced by 65% in the treatment group compared to the vehicle control [1] - Carrageenan-induced paw edema suppression: Male Swiss-Webster mice were administered IL-1R antagonist (5 mg/kg or 10 mg/kg, s.c.) 30 minutes before subplantar injection of carrageenan (1% w/v). Paw volume was measured at 4 hours post-carrageenan injection: 5 mg/kg reduced edema by 42%, and 10 mg/kg by 58%, showing dose-dependent efficacy [1] |
| Enzyme Assay |
NF-κB luciferase reporter assay: HEK293 cells were stably transfected with IL-1R expression plasmid and a NF-κB-responsive luciferase reporter plasmid. Cells were seeded in 96-well plates (2×10⁴ cells/well) and incubated overnight. Serial dilutions of IL-1R antagonist (0.1 μM–50 μM) were added, followed by stimulation with IL-1β (10 ng/mL) for 6 hours. Luciferase activity was measured using a luminometer, and IC50 was calculated by fitting dose-response curves [1]
- Surface Plasmon Resonance (SPR) binding assay: Recombinant human IRAK TIR domain was immobilized on a sensor chip. Serial concentrations of IL-1R antagonist (0.5 μM–20 μM) were injected over the chip, and binding affinity was analyzed by measuring changes in resonance units. The compound showed specific binding to IRAK TIR domain with a KD value of 3.7 μM [1] |
| Cell Assay |
Human PBMC cytokine secretion assay: PBMCs were isolated from healthy donors and seeded in 24-well plates (1×10⁶ cells/well) in RPMI medium. Cells were pretreated with IL-1R antagonist (0.1 μM–20 μM) for 1 hour, then stimulated with IL-1β (5 ng/mL) for 24 hours. Culture supernatants were collected, and IL-6/IL-8 concentrations were quantified by enzyme-linked immunosorbent assay (ELISA) [1]
- Western blot for signaling pathway analysis: HEK293 cells expressing IL-1R were seeded in 6-well plates (5×10⁵ cells/well) and pretreated with IL-1R antagonist (10 μM) for 1 hour, followed by IL-1β stimulation (10 ng/mL) for 0–60 minutes. Cells were lysed, and proteins were separated by SDS-PAGE, transferred to membranes, and probed with antibodies against phosphorylated ERK1/2, JNK, p38 (MAPK pathway), and phosphorylated IκBα (NF-κB pathway). β-actin was used as a loading control [1] |
| Animal Protocol |
Acute inflammation model: C57BL/6 mice (6–8 weeks old, n=5 per group) were randomly assigned to vehicle control and IL-1R antagonist treatment groups. The compound was dissolved in PBS containing 10% DMSO, administered intraperitoneally (i.p.) at 10 mg/kg 1 hour before i.p. injection of IL-1β (1 μg/mouse in PBS). Blood samples were collected via retro-orbital plexus 2 hours post-IL-1β injection, and serum was separated for IL-6 ELISA [1]
- Paw edema model: Male Swiss-Webster mice (n=6 per group) were anesthetized lightly. IL-1R antagonist (5 mg/kg or 10 mg/kg) was dissolved in PBS containing 10% DMSO and administered subcutaneously (s.c.) 30 minutes before subplantar injection of 1% carrageenan (50 μL/ paw). Paw volume was measured using a plethysmometer at 0 (baseline) and 4 hours post-carrageenan injection, and edema volume was calculated as (4-hour volume – baseline volume) [1] |
| Toxicity/Toxicokinetics |
Acute toxicity observation: Mice were treated with a single dose of up to 50 mg/kg of IL-1R antagonist (intraperitoneal or subcutaneous injection) and no acute toxic symptoms (drowsiness, loss of appetite, abnormal behavior) appeared within 7 days. Their body weight remained stable and there was no significant difference compared with the solvent group [1].
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| References | |
| Additional Infomation |
Background: Interleukin-1 (IL-1) is a key pro-inflammatory cytokine involved in the pathogenesis of various inflammatory diseases, such as rheumatoid arthritis, sepsis, and psoriasis. IL-1R-mediated signaling activates the NF-κB and MAPK pathways, leading to the production of pro-inflammatory cytokines and chemokines [1]
- Mechanism of action: IL-1R antagonists mimic the TIR domain of IL-1R and competitively bind to IRAK with MyD88. This compound blocks the assembly of the IL-1R signaling complex, inhibits downstream pro-inflammatory signaling cascades, and does not bind directly to IL-1 ligands [1] - Advantages over natural antagonists: Unlike natural IL-1R antagonists (e.g., recombinant protein anaspirin), this compound is a low molecular weight molecule with the potential for oral administration and higher bioavailability (not confirmed in this study) [1] - Therapeutic potential: This compound shows promising potential in the treatment of IL-1-mediated inflammatory diseases, and its in vivo efficacy in acute inflammation and claw edema models supports its further development as an anti-inflammatory drug [1] |
| Molecular Formula |
C18H26N2O2
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|---|---|
| Molecular Weight |
302.418
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| Exact Mass |
302.199
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| Elemental Analysis |
C, 71.49; H, 8.67; N, 9.26; O, 10.58
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| CAS # |
566914-00-9
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| PubChem CID |
10447660
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| Appearance |
Colorless to light yellow a solution in ethanol (100mg/mL)
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| LogP |
2.711
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
22
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| Complexity |
369
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC([C@H](NC(CCC1=CC=CC=C1)=O)C(N2CCCC2)=O)C
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| InChi Key |
DAZSWUUAFHBCGE-KRWDZBQOSA-N
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| InChi Code |
InChI=1S/C18H26N2O2/c1-14(2)17(18(22)20-12-6-7-13-20)19-16(21)11-10-15-8-4-3-5-9-15/h3-5,8-9,14,17H,6-7,10-13H2,1-2H3,(H,19,21)/t17-/m0/s1
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| Chemical Name |
N-[(1S)-2-methyl-1-(1-pyrrolidinylcarbonyl)propyl]-benzenepropanamide
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| Synonyms |
TLR1IL-1R Antagonist
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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 (~330.68 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.27 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 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 (8.27 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 25.0 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (8.27 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3067 mL | 16.5333 mL | 33.0666 mL | |
| 5 mM | 0.6613 mL | 3.3067 mL | 6.6133 mL | |
| 10 mM | 0.3307 mL | 1.6533 mL | 3.3067 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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