BQ-788
Names
Biological Activity
[Description]:
BQ-788 is a potent, selective ETB receptor antagonist with IC50 of 1.2 nM for inhibition of ET-1 binding to human Girardi heart cells, poorly inhibiting the binding to ETA receptors in human neuroblastoma cell line SK-N-MC cells with IC50 of 1300 nM.
[Related Catalog]:
[Target]
IC50: 1.2 nM (ETB)
[In Vitro]
BQ-788 potently and competitively inhibits 125I-labeled ET-1 binding to ETB receptors in human Girrardi heart cells (hGH) with an IC50 of 1.2 nM, but only poorly inhibits the binding to ETA receptors in human neuro-blastoma cell line SK-N-MC cells (IC50, 1300 nM). BQ-788 shows no agonistic activity up to 10 μM and competitively inhibits thevasoconstriction induced by an ETB-selective agonist (pA2, 8.4). BQ-788 also inhibits several bioactivities of ET-1, such as bronchoconstriction, cell proliferation, and clearance of perfused ET-1[1].
[In Vivo]
BQ-788 (3 mg/kg/h, i.v.) completely inhibits a pharmacological dose of ET-1- or sarafotoxin6c (0.5 nmol/kg, i.v.)-induced ETB receptor-mediated depressor, but not pressor responses in conscious rats. Furthermore, BQ-788 markedly increases the plasma concentration of ET-1, which is considered an index of potential ETB receptor blockade in vivo. In Dahl salt-sensitive hypertensive (DS) rats, BQ-788 (3 mg/kg/h, i.v.) increases blood pressure by about 20 mm Hg. It is reported that BQ-788 also inhibits ET-1-induced bronchoconstriction, tumor growth and lipopolysaccharide-induced organfailure[1]. BQ 788 (3 mg/kg) results in an eightfold leftward shift in the ET-1 dose-response curve, suggesting a significant involvement of ETB dilator receptors[2]. Mice are treated with 30 nmol BQ-788 by intraplantar, reduce mechanical hyperalgesia (47% and 42%), thermal hyperalgesia (68% and 76%), oedema (50% and 30%); myeloperoxidase activity (64% and 32%), and overt-pain like behaviours. Additionally, intraplantar treatment with clazosentan or BQ-788 decreases spinal (45% and 41%) and peripheral (47% and 47%) superoxide anion production as well as spinal (47% and 47%) and peripheral (33% and 54%) lipid peroxidation, respectively[3].
[References]
[Related Small Molecules]
BQ-788 (sodium salt)
|
Endothelin-1 (human, bovine, dog, mouse, porcine, rat) acetate salt
|
Atrasentan hydrochloride
|
BQ-123
|
Zibotentan (ZD4054)
|
ACT-132577
|
RE 201
|
Atrial Natriuretic Factor (1-28) (mouse, rabbit, rat) trifluoroacetate salt
|
Avosentan
|
Sitaxentan sodium
|
IRL-1620 TFA
|
Sulfisoxazole
|
Aminaftone
|
PD-159020
|
Ro 46-2005
Chemical & Physical Properties
[ Molecular Formula ]:
C34H51N5O7
[ Molecular Weight ]:
641.79800
[ Exact Mass ]:
641.37900
[ PSA ]:
159.07000
[ LogP ]:
5.93060
[ Storage condition ]:
2-8℃