| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
native human bradykinin B1 receptor ( Ki = 0.26 nM )
ELN441958 targets the bradykinin B1 receptor (B1R), a G-protein coupled receptor with the principal ligand bradykinin. The B1 receptor plays an important role in chronic pain and inflammation. As a neutral, competitive antagonist, ELN441958 inhibits the binding of the B1 agonist ligand to the receptor. It is highly selective for B1 over B2 receptors, minimizing off-target effects. The compound's higher potency at primate receptors is relevant for translational research. |
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| ln Vitro |
ELN-441958 exhibits primate selectivity over rodent B1 receptors, possessing a human rank order potency (KB, nanomolar) of 0.12 ± 0.02. Rat (1.5 ± 0.4) < mouse (14 ± 4) > rhesus monkey (0.24 ± 0.01)[1].
ELN-441958 exhibits excellent metabolic stability and permeability[1]. In vitro, ELN441958 competitively inhibits the binding of the agonist [³H]DAKD to the human B1 receptor in IMR-90 lung fibroblast cell membranes with a Ki of 0.26 nM. It is up to 120-fold more potent at primate B1 receptors than at rodent B1 receptors. The compound shows high selectivity for B1 over B2 receptors. These properties make it a valuable tool for studying B1 receptor function in pain and inflammation. |
| ln Vivo |
ELN-441958 (1–10 mg/kg; s.c.; once) dose-dependently reduces carrageenan-induced thermal hyperalgesia in a rhesus monkey tail-withdrawal model[1].
ELN-441958 (0–10 mg/kg; i.v. or p.o.) shows a good pharmacokinetic profile in the rat and rhesus monkey[1]. In vivo, ELN441958 shows significant systemic efficacy in treating inflammatory pain in rhesus monkeys. It has high oral bioavailability and low CNS exposure in mice. The compound's efficacy in primate models of inflammatory pain supports its potential therapeutic application for chronic pain conditions. Its high oral bioavailability enables convenient oral administration. The low CNS exposure may reduce central side effects. |
| Enzyme Assay |
In vitro receptor binding assays for ELN441958 use membrane preparations from IMR-90 lung fibroblast cells expressing native human bradykinin B1 receptors. Radiolabeled agonist [³H]DAKD is used as a tracer. Various concentrations of ELN441958 are incubated with membranes and radioligand. Bound radioactivity is measured by scintillation counting. Ki values are calculated from competition binding curves. Selectivity for B1 over B2 receptors is assessed using B2-expressing cells.
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| Cell Assay |
Cellular assays for ELN441958 use IMR-90 lung fibroblast cells or other cells expressing the bradykinin B1 receptor. Receptor activation is assessed by measuring downstream signaling such as calcium mobilization or ERK phosphorylation following B1 agonist stimulation. Cells are treated with various concentrations of ELN441958 prior to agonist stimulation. Inhibition of signaling is quantified. These assays confirm the compound's antagonist activity.
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| Animal Protocol |
Adult male and female rhesus monkeys
1, 3, or 10 mg/kg Subcutaneous injection, 30 min before carrageenan injection In vivo animal studies for ELN441958 utilize models of inflammatory pain in primates (rhesus monkeys) as well as rodent models. The compound is administered orally at various doses. Pain responses are measured using behavioral endpoints (e.g., paw withdrawal thresholds, hyperalgesia). Inflammatory markers may be assessed. Pharmacokinetic and pharmacodynamic sampling is performed to correlate exposure with efficacy. Efficacy is compared to vehicle and reference analgesics. |
| ADME/Pharmacokinetics |
ELN441958 has high oral bioavailability. As a small molecule with molecular weight of approximately 520 g/mol (C₂₉H₂₉ClN₄O₂), it is orally absorbed and distributed. It has low CNS exposure in mice, suggesting limited brain penetration. The compound's pharmacokinetic profile supports once-daily oral dosing for pain indications. Detailed PK parameters would be determined in preclinical and clinical studies. Its high oral bioavailability is a key feature for development.
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| Toxicity/Toxicokinetics |
Preclinical toxicity of ELN441958 is not extensively documented in publicly available sources. As a B1 receptor antagonist, potential adverse effects may include effects on the kallikrein-kinin system, which is involved in inflammation, blood pressure regulation, and pain. Standard toxicology studies would evaluate safety pharmacology, genotoxicity, and repeat-dose toxicity. The compound's high oral bioavailability and low CNS exposure suggest a favorable safety profile.
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| References | |
| Additional Infomation |
ELN441958 is a potent, selective, orally bioavailable bradykinin B1 receptor antagonist with a Ki of 0.26 nM. It shows significant efficacy in primate models of inflammatory pain. It is highly selective for B1 over B2 receptors and is more potent at primate than rodent receptors. It is available for research purposes only.
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| Molecular Formula |
C29H29CLN4O2
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|---|---|
| Molecular Weight |
501.01916
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| Exact Mass |
500.198
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| Elemental Analysis |
C, 69.52; H, 5.83; Cl, 7.08; N, 11.18; O, 6.39
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| CAS # |
913064-47-8
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| Related CAS # |
913064-47-8
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| PubChem CID |
11848206
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| Appearance |
White to off-white solid powder
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| LogP |
5.486
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
36
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| Complexity |
799
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(N1CCC2(CCN(C3C=CN=CC=3)CC2)CC1)C1C=C(N2CC3C(=C(C=CC=3)Cl)C2=O)C=CC=1
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| InChi Key |
ARYQHSWJGHCGJS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H29ClN4O2/c30-25-6-2-4-22-20-34(28(36)26(22)25)24-5-1-3-21(19-24)27(35)33-17-11-29(12-18-33)9-15-32(16-10-29)23-7-13-31-14-8-23/h1-8,13-14,19H,9-12,15-18,20H2
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| Chemical Name |
7-chloro-2-[3-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)phenyl]-3H-isoindol-1-one
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| Synonyms |
ELN-441958; ELN441958; ELN 441958
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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: 50~100 mg/mL (99.8~199.6 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.99 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 (4.99 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 (4.99 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 | 1.9959 mL | 9.9796 mL | 19.9593 mL | |
| 5 mM | 0.3992 mL | 1.9959 mL | 3.9919 mL | |
| 10 mM | 0.1996 mL | 0.9980 mL | 1.9959 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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