KR-31064의 수용체-리간드 결합특성에 대한 연구

Receptor-Ligand Binding Characteristics of KR-31064

KR-31064 was developed for the strong angiotensin II receptor antagonist among the one of pyridyl imidazol series compounds. To investigate the receptor-ligand binding characteristics of this nonpeptide antagonist, binding exper-iments were deployed in various conditions and ex vivo contractile responses were tested toward the standard compound,losartan. Receptor binding experiments with radiolabeled angiotensin II, the IC50 value for KR-31064 resulted 0.67 nM with-out any activities toward type 2 angiotensin II receptor. The comparative potency against losartan was more than 18 foldand the specific activity in type 1 angiotensin II receptor was more than 10,000 fold comparing to the type 2 receptor. Scat-chard analysis of saturation binding data showed KR-31064 acted on the receptor in a competitive mode. KR-31064 inhibited the contractile response derived by angiotensin II (pKB: 9.86) similar to that of losartan with decreased maximum signals. As a potent and specific type 1 angiotensin II receptor antagonist, KR-31064 may have possibilities for the development of diagnostic ligands that can be used as tools for various biochemical research experiments and non-invasive diagnostics.