ELN441958Potent and selective bradykinin B1 receptor antagonist CAS# 913064-47-8 |
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Quality Control & MSDS
3D structure
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Number of papers citing our products
| Cas No. | 913064-47-8 | SDF | Download SDF |
| PubChem ID | 11848206 | Appearance | Powder |
| Formula | C29H29ClN4O2 | M.Wt | 501.02 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : 100 mg/mL (199.59 mM; Need ultrasonic) | ||
| Chemical Name | 7-chloro-2-[3-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)phenyl]-3H-isoindol-1-one | ||
| SMILES | C1CN(CCC12CCN(CC2)C(=O)C3=CC(=CC=C3)N4CC5=C(C4=O)C(=CC=C5)Cl)C6=CC=NC=C6 | ||
| Standard InChIKey | ARYQHSWJGHCGJS-UHFFFAOYSA-N | ||
| Standard InChI | 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 | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | ELN-441958 is a potent, neutral antagonist of B1 receptor, inhibits the binding of the B1 agonist ligand [3H]DAKD to IMR-90 cells with Ki of 0.26 nM. ELN-441958 is highly selective for B1 over B2 receptors, and >500/ 2000-fold selective for the B1 over μ/δ-opioid receptor.
IC50 value: 0.26 nM (Ki)
Target: B1 Receptor
in vitro: ELN-441958 is a novel small molecule bradykinin B1 receptor antagonist, based on the inhibition of agonist-induced increases in intracellular calcium in native and recombinant cells. ELN-441958 does not inhibit the activation of the human bradykinin B2 receptor at concentrations up to 10 μM, showing that it is highly selective for B1 over B2 receptors. ELN-441958 also displays good selectivity for B1 over other receptors examined in a broad screening panel. It is >500-fold and >2000-fold selective for the B1 receptor over the human μ- and δ-opioid receptor, the most potent off-target activity identified. In IMR-90 cells expressing the native human B1 receptor, ELN-441958 produced a concentration-dependent antagonism of the DAKD-induced calcium mobilization with a KB of 0.12 nM. [1]
in vivo: ELN-441958 is essentially completely absorbed and produces high plasma levels after oral administration in rhesus monkeys.ELN-441958 has a moderate clearance and volume of distribution in both species following i.v. administration, consistent with the high metabolic stability in rat, rhesus, and human microsomes. ELN-441958 has high oral exposure and moderate plasma half-lives in rats and rhesus monkeys. The oral availability of ELN441958 in rats was 57%. ELN-441958 dose-dependently reduced carrageenan-induced thermal hyperalgesia in a rhesus monkey tail-withdrawal model, with an ED50 3 mg/kg s.c. [1] References: | |||||
ELN441958 Dilution Calculator
ELN441958 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 1.9959 mL | 9.9796 mL | 19.9593 mL | 39.9186 mL | 49.8982 mL |
| 5 mM | 0.3992 mL | 1.9959 mL | 3.9919 mL | 7.9837 mL | 9.9796 mL |
| 10 mM | 0.1996 mL | 0.998 mL | 1.9959 mL | 3.9919 mL | 4.9898 mL |
| 50 mM | 0.0399 mL | 0.1996 mL | 0.3992 mL | 0.7984 mL | 0.998 mL |
| 100 mM | 0.02 mL | 0.0998 mL | 0.1996 mL | 0.3992 mL | 0.499 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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ELN441958 is a novel, potent and selective bradykinin B1 receptor antagonist with Ki value of 0.26 nM [1].
The bradykinin B1 receptor is a G-protein coupled receptor with principal ligand of bradykinin and plays an important role in chronic pain and inflammation [1].
ELN441958 is a novel, potent and selective bradykinin B1 receptor antagonist. In IMR-90 lung fibroblast cell membranes, ELN441958 competitively inhibited the binding of the agonist [3H]DAKD to the human B1 receptor with Ki value of 0.26 nM. In IMR-90 cells expressing the native human B1 receptor, ELN441958 concentration-dependently antagonized calcium mobilization induced by DAKD with KB value of 0.12 nM. ELN441958 is highly selective for B1 over B2 receptors. ELN441958 failed to inhibit the calcium mobilization induced by B2-receptor agonist BK. ELN441958 also inhibited human μ-, δ-, κ- opioid receptors and muscarinic M1 receptor with Ki values of 0.13, 0.69, 1.5 and 0.37 μM, respectively. ELN441958 is also an agonist at the δ-opioid receptor (EC50 = 0.76 μM) and μ-opioid receptor. In vitro, ELN441958 exhibited good permeability and metabolic stability [1].
In rats and rhesus monkeys, ELN441958 exhibited high oral bioavailability and moderate plasma half-lives. In rhesus monkeys, ELN441958 dose-dependently reduced the thermal hyperalgesia induced by carrageenan with ED50 value of ~3 mg/kg s.c [1].
Reference:
[1]. Hawkinson JE, Szoke BG, Garofalo AW, et al. Pharmacological, pharmacokinetic, and primate analgesic efficacy profile of the novel bradykinin B1 Receptor antagonist ELN441958, J Pharmacol Exp Ther, 2007, 322(2): 619-630.
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Pharmacological, pharmacokinetic, and primate analgesic efficacy profile of the novel bradykinin B1 Receptor antagonist ELN441958.[Pubmed:17470643]
J Pharmacol Exp Ther. 2007 Aug;322(2):619-30.
The bradykinin B(1) receptor plays a critical role in chronic pain and inflammation, although efforts to demonstrate efficacy of receptor antagonists have been hampered by species-dependent potency differences, metabolic instability, and low oral exposure of current agents. The pharmacology, pharmacokinetics, and analgesic efficacy of the novel benzamide B(1) receptor antagonist 7-chloro-2-[3-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecanecarbonyl)phenyl]-2,3-dih ydro-isoindol-1-one (ELN441958) is described. ELN441958 competitively inhibited the binding of the B(1) agonist ligand [(3)H]desArg(10)-kallidin ([(3)H]DAKD) to IMR-90 human fibroblast membranes with high affinity (K(i) = 0.26 +/- 0.02 nM). ELN441958 potently antagonized DAKD (but not bradykinin)-induced calcium mobilization in IMR-90 cells, indicating that it is highly selective for B(1) over B(2) receptors. Antagonism of agonist-induced calcium responses at B(1) receptors from different species indicated that ELN441958 is selective for primate over rodent B(1) receptors with a rank order potency (K(B), nanomolar) of human (0.12 +/- 0.02) approximately rhesus monkey (0.24 +/- 0.01) > rat (1.5 +/- 0.4) > mouse (14 +/- 4). ELN441958 had good permeability and metabolic stability in vitro consistent with high oral exposure and moderate plasma half-lives in rats and rhesus monkeys. Because ELN441958 is up to 120-fold more potent at primate than at rodent B(1) receptors, it was evaluated in a primate pain model. ELN441958 dose-dependently reduced carrageenan-induced thermal hyperalgesia in a rhesus monkey tail-withdrawal model, with an ED(50) approximately 3 mg/kg s.c. Naltrexone had no effect on the antihyperalgesia produced by ELN441958, indicating a lack of involvement of opioid receptors. ELN441958 is a novel small molecule bradykinin B(1) receptor antagonist exhibiting high oral bioavailability and potent systemic efficacy in rhesus monkey inflammatory pain.
