ELN 441958

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

ELN-441958 是一种有效的 B1 受体中性拮抗剂，抑制 B1 激动剂配体 [3H]DAKD 与 IMR-90 细胞的结合，Ki 为 0.26 nM。

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 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.

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 monkeysDosage: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%.

ELN441958 | ELN 441958 | ELN-441958

GPCR/G Protein

Bradykinin Receptor

B1 Receptor

Cancer

——

913064-47-8

501.02

C29H29ClN4O2

>98% (HPLC)

DMSO: 10 mM

O=C1N(C2=CC=CC(C(N3CCC4(CCN(C5=CC=NC=C5)CC4)CC3)=O)=C2)CC6=C1C(Cl)=CC=C6

7-Chloro-2-[3-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)phenyl]-3H-isoindol-1-one

(-20℃)

With Ice Pack

≥ 2 years