Tezosentan (RO 610612) is an endothelin (ET) receptor antagonist, with pA₂s of 9.5, 7.7 for ET_A and ET_B receptors, respectively.

Affinity of Tezosentan for the ET receptors is assessed in different cells and tissues. Tezosentan inhibits the specific ¹²⁵I-labeled ET-1 binding to ETA receptors with an inhibitory potency (K_i) of 0.3 nM on CHO cells and of 18 nM on membranes of baculovirus-infected insect cells. Similarly, Tezosentan inhibits the specific binding of ¹²⁵I-labeled ET-1, ET-3, or sarafotoxin S6c to ET_B receptors with an inhibitory affinity of 10 to 21 nM. Tezosentan up to a concentration of 1 μM did not exhibit any binding inhibitory activity in 27 radioligand binding assays different from ET binding. On H1 central, 5-hydroxytryptamine2A, and vasopressin V1 receptors, Tezosentan (1 μM) induces a weak inhibition of less than 20%^[1].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

In pithed Wistar rats, Tezosentan dose-dependently inhibits the pressor effect of big ET-1 (P<0.001 at all doses). At the lowest dose tested of 1 mg/kg, Tezosentan inhibits the pressor effect of the various doses of big ET-1 by 50 to 80%. Tezosentan has no effect by itself on blood pressure in these pithed rats. Tezosentan is very effective in a rat model of acute renal failure. ET antagonists have been shown to prevent the vasoconstriction and the renal failure that follow acute renal ischemia in rats^[1].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

605.63

C₂₇H₂₇N₉O₆S

180384-57-0

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Clozel M, et al. Pharmacology of tezosentan, new endothelin receptor antagonist designed for parenteral use. J Pharmacol Exp Ther. 1999 Aug;290(2):840-6.

Rats^[1]
A pseudocrush syndrome is simulated by injection of i.m. glycerol. A control group does not receive glycerol and is used as a reference. Tezosentan or bosentan for comparison or saline as control is injected as two bolus i.v. doses of 10 mg/kg 1 h and 20 min before glycerol. Rats are allowed to recover for 2 h and then are placed in individual metabolic cages for 48 h. Blood samples withdraw from a catheter placed in the abdominal aorta and urine free of food and feces are collected at 24 and 48 h. Plasma and urinary creatinine levels are measured with a centrifugal analyzer. Renal function is assessed by calculating creatinine clearance at 24 and 48 h after glycerol administration^[1].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Clozel M, et al. Pharmacology of tezosentan, new endothelin receptor antagonist designed for parenteral use. J Pharmacol Exp Ther. 1999 Aug;290(2):840-6.