SSR240612 is a potent and selective non-peptide bradykinin B1 receptor antagonist with Kis of 0.48 nM and 0.73 nM for B1 kinin receptors of human fibroblast MRC5 and HEK cells expressing human B1 receptors, 481 nM and 358 nM for B2 receptors of guinea pig ileum membranes and CHO cells expressing human B1 receptor, respectively.
SSR240612 is a novel non-peptide antagonist of the bradykinin B1 receptor, with 500-1,000 fold selectivity for B1 over B2. It could inhibit the binding of peptide [3H]Lys0-des-Arg9-BK to bradykinin B1 receptor with Ki values of 0.48 and 0.73 nM for human fibroblast MRC5 and human embryonic kidney cells expressing recombinant human B1 receptor, respectively. SSR240612 antagonized Lys0-desAr9-BK both in vitro and in vivo. It inhibited Lys0-desAr9-BK-induced inositol monophosphate formation in MRC5 with an IC50 of 1.9 nM. Administration of SSR240612 at dose of 3 and 10 mg/kg p.o., or 0.3 and 1 mg/kg i.p., inhibited desAr9-BK-induced paw edema in mice[1]. Oral administration of SSR240612 at dose of 10mg/kg once daily for 7 days reversed low state inflammation in adipose tissue and plasma fatty acids changes associated with insulin resistance in glucose-fed rats[2].
作用机制
SSR240612 is a competitive inhibitor of bradykinin B1 receptor.[1]
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