ELN 441958

SKU: orb1223667

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.

Key Properties

• CAS Number: 913064-47-8
• MW: 501.02
• Purity: >98% (HPLC)
• Formula: C₂₉H₂₉ClN₄O₂
• SMILES: O=C1N(C2=CC=CC(C(N3CCC4(CCN(C5=CC=NC=C5)CC4)CC3)=O)=C2)CC6=C1C(Cl)=CC=C6
• Target: Bradykinin Receptor
• Solubility: DMSO: 10 mM

Bioactivity

• In Vivo:
  ELN-441958 (1-10 mg/kg; s. c. ; once) dose-dependently reduces carrageenan-induced thermal hyperalgesia in a rhesus monkey tail-withdrawal model. ELN-441958 (0-10 mg/kg; i. v. or p.o.) exhibits a favorable pharmacokinetic profile in the rat and rhesus monkey. Animal model: Adult male and female rhesus monkeys. Dosage: 1, 3, or 10 mg/kg. Administration: Subcutaneous injection, 30 min before carrageenan injection. Result: Increased the tail-withdrawal latencies in a dose-dependent manner. Animal model: Rhesus monkeys or Sprague-Dawley rats. Dosage: 2.5 or 10 mg/kg for rats, 1 mg/kg or 5 mg/kg for rhesus monkeys. Administration: Intravenous injection (2.5 mg/kg and 1 mg/kg) or oral administration (10 mg/kg and 5 mg/kg) (Pharmacokinetic Analysis). Result: In rats: When dosed intravenously, showed a moderate volume of distribution (2.7 L/kg, approximately four times total body water) and a moderate clearance (0.96 L/h/kg, approximately 24% of hepatic blood flow). The terminal plasma half-life of this compound in rats was 1.7 h. When dosed orally, the concentrations increased to a maximum of 1.2 g/mL at 2 h after dosing. The oral availability was 57%. In rhesus monkeys: When dosed intravenously, showed a moderate volume of distribution (2.7 L/kg) and a moderate clearance (0.49 L/h/kg, approximately 32% of hepatic blood flow). The terminal plasma half-life was 3.9 h. When dosed orally, the concentrations increased to a maximum of 3.6 g/mL at 3.3 h after dosing. The calculated oral bioavailability was greater than 100%.
• In Vitro:
  ELN-441958 is selective for primate over rodent B1 receptors with a rank order potency (KB, nanomolar) of human (0.12 ± 0.02) ~ rhesus monkey (0.24 ± 0.01) > rat (1.5 ± 0.4) > mouse (14 ± 4). ELN-441958 has good permeability and metabolic stability.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

ELN441958 | ELN 441958 | ELN-441958

Quick Database Links

Gene Symbol

Bradykinin Receptor