YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
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Receptor-Ligand Binding Characteristics of KR-31064

KR-31064의 수용체-리간드 결합특성에 대한 연구

  • Lee, Sunghou (Dept. of Biomedical Technology, Sangmyung University)
  • 이승호 (상명대학교 천안캠퍼스 공과대학 의생명공학과)
  • Received : 2014.01.10
  • Accepted : 2014.01.21
  • Published : 2014.02.28
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Abstract

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 experiments 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 $IC_{50}$ value for KR-31064 resulted 0.67 nM without any activities toward type 2 angiotensin II receptor. The comparative potency against losartan was more than 18 fold and the specific activity in type 1 angiotensin II receptor was more than 10,000 fold comparing to the type 2 receptor. Scatchard 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 ($pK_B$: 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.

Keywords

References

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