RES-1149-1 and -2, novel non-peptidic endothelin type B receptor antagonists produced by Aspergillus sp. III. Biochemical properties of RES-1149-1, -2 and structure-activity relationships.
RES-1149-1 and -2, produced by Aspergillus sp. RE-1149, were found to be non-peptidic antagonists for endothelin type B receptor (ET(B) receptor). RES-1149-1 and -2 selectively inhibited the endothelin-1 (ET-1) binding to ET(B) receptor in a competitive manner with IC50 values of 1.5 microM and 20 microM, respectively. RES-1149-1 inhibited the increase in intracellular Ca2+ concentration elicited by 1 nM ET-1 in COS-7 cells expressing human ET(B) receptor, but not in the case of cells expressing ET(A) receptor. In addition, some structure-activity relationships are described.
Ogawa
T
T
Kyowa Hakko Kogyo Co., Ltd., Tokyo, Japan.
Uosaki
Y
Y
Tanaka
T
T
Tsukuda
E
E
Mihara
A
A
Matsuda
Y
Y
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000378:metabolism; D006801:Humans; D011817:Rabbits; D051381:Rats; D044023:Receptor, Endothelin B; D013045:Species Specificity; D013329:Structure-Activity Relationship; D013552:Swine; D013764:Tetrahydronaphthalenes / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; C098351:RES 1149-1; C098352:RES 1149-2; D044023:Receptor, Endothelin B; D013764:Tetrahydronaphthalenes; D002118:Calcium