Unique binding behavior of azilsartan compared with candesartan


eMediNexus    16 December 2017

The angiotensin II type 1 (AT(1)) receptor blocker (ARB) candesartan is known to strongly reduce blood pressure (BP) in patients with hypertension and has cardioprotective effects. Azilsartan has been found to provide a more potent 24-h sustained antihypertensive effect in comparison with candesartan. A report was published in Hypertension Research that evaluated the molecular interactions of azilsartan with the AT(1) receptor that could possibly explain its robust BP-lowering activity. Researchers assessed the binding affinities of ARBs for the AT(1) receptor and their inverse agonist activity toward the production of inositol phosphate (IP). Docking models were constructed for the interactions between ARBs and the receptor. Azilsartan has a unique moiety, a 5-oxo-1,2,4-oxadiazole, in place of a tetrazole ring, unlike candesartan. Both the ARBs interact with the same sites in the AT(1) receptor (Tyr(113), Lys(199) and Gln(257)); however, the hydrogen bonding between the oxadiazole of azilsartan-Gln(257) is stronger than that between the tetrazole of candesartan-Gln(257). Researchers speculated that azilsartan has a unique binding behavior to the AT(1) receptor due to its 5-oxo-1,2,4-oxadiazole moiety and induces stronger inverse agonism. This property of azilsartan could explain its superior BP-lowering efficacy compared with candesartan and other ARBs.

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