SB 657510

Names

[ Name ]:
SB 657510

[Synonym ]:
Benzenesulfonamide,2-bromo-N-[4-chloro-3-[[(3R)-1-methyl-3-pyrrolidinyl]oxy]phenyl]-4,5-dimethoxy
2-Bromo-N-[4-chloro-3-[[(3R)-1-methyl-3-pyrrolidinyl]oxy]phenyl]-4,5-dimethoxy-benzenesulfonamide

Biological Activity

[Description]:

SB-657510 is a selective urotensin II (UII) receptor (UT) antagonist. The Ki values are 61, 17, 30, 65 and 56 nM for human, monkey, cat, rat and mouse receptors, respectively. SB-657510 exerts anti-inflammatory effects by inhibiting UII-induced upregulation of inflammatory mediators such as adhesion molecules, cytokines, and tissue factor in human vascular endothelial cells[1][2].

[Related Catalog]:

Signaling Pathways >> Others >> Others

Research Areas >> Inflammation/Immunology

[In Vitro]

SB-657510 dramatically blocks the UII-induced increase in adhesion between U937 and EA.hy926 cell. SB-657510 (1 μM; 0.5-8 hours) blocks the expression of tissue factor induced by UII in endothelial cells[1]. SB-706375 (1-10000 nM) inhibits [Ca2+]i mobilization elicited by 10 nM hU-II with an IC50 of 180 nM[2]. Western Blot Analysis[1] Cell Line: EA.hy926 cells (UII-induced) Concentration: 1 μM Incubation Time: 0.5, 1, 2, 4, 8 hours Result: Remarkably decreased the UII-induced protein expression of tissue factor.

[In Vivo]

SB-657510 inhibits the progression of high-fat diet induced atherosclerosis and diabetes-associated atherosclerosis[1]. Levels of phosphorylated ERK are significantly attenuated in the aorta of SB-657510-treated (30 mg/kg/day) diabetic mice (Male Apoe KO mice)[3].

[References]

[1]. Park SL, et al. Inhibitory Effect of an Urotensin II Receptor Antagonist on Proinflammatory Activation Inducedby Urotensin II in Human Vascular Endothelial Cells. Biomol Ther (Seoul). 2013 Jul 30;21(4):277-83.

[2]. Behm DJ, et al. Palosuran inhibits binding to primate UT receptors in cell membranes but demonstrates differential activity in intact cells and vascular tissues. Br J Pharmacol. 2008 Oct;155(3):374-86.

[3]. Watson AM, et al. Urotensin II receptor antagonism confers vasoprotective effects in diabetes associated atherosclerosis: studies in humans and in a mouse model of diabetes. Diabetologia. 2013 May;56(5):1155-65.

Chemical & Physical Properties

[ Molecular Formula ]:
C₁₉H₂₂BrClN₂O₅S

[ Molecular Weight ]:
505.81000

[ Exact Mass ]:
504.01200

[ PSA ]:
85.48000

[ LogP ]:
5.09510

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H315-H319-H335

[ Precautionary Statements ]:
P261-P305 + P351 + P338

[ Hazard Codes ]:
Xi

[ RIDADR ]:
NONH for all modes of transport

Articles

Urotensin II receptor antagonism confers vasoprotective effects in diabetes associated atherosclerosis: studies in humans and in a mouse model of diabetes.

Diabetologia 56(5) , 1155-65, (2013)

The small, highly conserved vasoactive peptide urotensin II (UII) is upregulated in atherosclerosis. However, its effects in diabetes-associated atherosclerosis have not been assessed.Endothelial cell...