ELN441958 is a potent, competitive, and selective bradykinin B1 receptor antagonist with a Ki value of 0.26nM [1]. ELN441958 can target Nsp12_ortho and Nsp12_Palm1 sites and has potential inhibitory activity against SARS-CoV-2 replication[2]. ELN441958 has been widely used to alleviate thermal hyperalgesia in animal models[3].
In vitro, ELN441958 treatment at 1µM for 4h significantly inhibited octapeptide [des-Arg9]-Bradykinin (DABK) (0.1µM; 4h)-induced PTGS2 expression in human amniotic fibroblasts (HAFs)[4].
In vivo, ELN441958 treatment via subcutaneous injection at a single dose of 1mg/kg for 30min reduced anxiety-like behavior in DBA/2NCrl mice[5].
References:
[1] Hawkinson J E, Szoke B G, Garofalo A W, et al. Pharmacological, pharmacokinetic, and primate analgesic efficacy profile of the novel bradykinin B1 Receptor antagonist ELN441958[J]. The Journal of pharmacology and experimental therapeutics, 2007, 322(2): 619-630.
[2] Gervasoni S, Manelfi C, Adobati S, et al. Target prediction by multiple virtual screenings: analyzing the SARS-CoV-2 phenotypic screening by the docking simulations submitted to the MEDIATE initiative[J]. International Journal of Molecular Sciences, 2023, 25(1): 450.
[3] Wisniewski P, Gangnus T, Burckhardt B B. Recent advances in the discovery and development of drugs targeting the kallikrein-kinin system[J]. Journal of translational medicine, 2024, 22(1): 388.
[4] Ni X, Wang W, Liu Y, et al. The bradykinin system contributes to the regulation of prostaglandin-endoperoxide synthase 2 expression in human amnion fibroblasts: Implications for term and preterm birth[J]. Frontiers in Endocrinology, 2022, 13: 873727.
[5] Rouhiainen A, Kulesskaya N, Mennesson M, et al. The bradykinin system in stress and anxiety in humans and mice[J]. Scientific reports, 2019, 9(1): 19437.
ELN441958是一种强效、竞争性且选择性的bradykinin B1受体拮抗剂，Ki值为0.26nM[1]。ELN441958可靶向Nsp12_ortho和Nsp12_Palm1位点，具有潜在的抑制SARS-CoV-2复制活性[2]。ELN441958已广泛用于缓解动物模型中的热痛觉过敏[3]。
在体外，使用1µM的ELN441958处理4小时，显著抑制了八肽[des-Arg9]-Bradykinin（DABK）（0.1µM；4h）诱导的人羊膜成纤维细胞（HAFs）中PTGS2的表达[4]。
在体内，以单剂量1mg/kg皮下注射ELN441958 30分钟，可减轻 DBA/2NCrl 小鼠的焦虑样行为[5]。