Azilsartan medoxomil monopotassium  (Synonyms: Azilsartan kamedoxomil; TAK 491 monopotassium)

Azilsartan medoxomil monopotassium is an orally administered angiotensin II receptor type 1 antagonist with IC50 of 0.62 nM, which used in the treatment of adults with essential hypertension. IC50 Value: 0.62 nM [2] Target: AT1 receptor in vitro: In aortic endothelial cells, azilsartan inhibited cell proliferation at concentrations as low as 1 μmol/l, whereas valsartan showed little or no antiproliferative effects at concentrations below 10 μmol/l. Antiproliferative effects of azilsartan were also observed in cells lacking AT1 receptors[1]. in vivo: Oral administration of 0.1-3 mg/kg olmesartan medoxomil reduced blood pressure; however, only the two highest doses significantly reduced blood pressure 24h after dosing. ED(25) values were 0.41 and 1.3 mg/kg for azilsartan medoxomil and olmesartan medoxomil, respectively [2]. Over a longer treatment period of 24 weeks, azilsartan medoxomil showed sustained BP-lowering efficacy, with the reduction in 24-hour mean SBP at week 24 significantly greater with azilsartan medoxomil 40 or 80 mg once daily than with valsartan 320 mg once daily. Mean reductions from baseline in mean clinic SBP and DBP as well as DBP by ABPM were also significantly greater with azilsartan medoxomil 40 or 80 mg once daily than with valsartan[3]. In 4 randomized controlled trials (3 published to date), azilsartan medoxomil/chlorthalidone 40 mg/12.5 mg and 40 mg/25 mg reduced blood pressure (BP) significantly more than comparators did, including an approximately 5-mm Hg greater BP reduction than olmesartan medoxomil/hydrochlorothiazide 40 mg/25 mg and azilsartan medoxomil/hydrochlorothiazide [4].

Azilsartan medoxomil (0.03-1 mg/kg, p.o.) monopotassium inhibits the angiotensin II-induced pressor response in normotensive rats^[2].
Azilsartan medoxomil (0.1-10 mg/kg in peanut butter, once daily) monopotassium inhibits vascular wall expression of plasminogen activator inhibitor type-I (PAI-1) protein, and potentially facilitates the stabilization of atherosclerotic plaques in ApoE knockout mice on a high fat diet rendered overexpressors of PAI-1 in VSMCs^[5].
Azilsartan medoxomil (0.03-10 mg/kg, oral gavage, once a day) monopotassium reduces myocardial infarct size in rats^[6].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

606.62

C₃₀H₂₃KN₄O₈

863031-24-7

Solid

White to off-white

O=C(C1=C2C(N=C(OCC)N2CC3=CC=C(C4=CC=CC=C4C5=NC(O[N-]5)=O)C=C3)=CC=C1)OCC6=C(C)OC(O6)=O.[K+]

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

• [1]. Kajiya T, Ho C, Wang J, Molecular and cellular effects of azilsartan: a new generation angiotensin II receptor blocker. J Hypertens. 2011 Dec;29(12):2476-83.  [Content Brief]

  [2]. Kusumoto K, Igata H, Ojima M, Antihypertensive, insulin-sensitising and renoprotective effects of a novel, potent and long-acting angiotensin II type 1 receptor blocker, azilsartan medoxomil, in rat and dog models.  [Content Brief]

  [3]. Perry CM. Azilsartan medoxomil: a review of its use in hypertension. Clin Drug Investig. 2012 Sep 1;32(9):621-39.  [Content Brief]

  [4]. Pierini D, Anderson KV. Azilsartan medoxomil/chlorthalidone: a new fixed-dose combination antihypertensive. Ann Pharmacother. 2013 May;47(5):694-703.  [Content Brief]

  [5]. French CJ, et al. The angiotensin receptor blocker, azilsartan medoxomil (TAK-491), suppresses vascular wall expression of plasminogen activator inhibitor type-I protein potentially facilitating the stabilization of atherosclerotic plaques. J Cardiovasc Pharmacol. 2011 Aug;58(2):143-8.  [Content Brief]

  [6]. Ye Y, et al. Additive effect of TAK-491, a new angiotensin receptor blocker, and pioglitazone, in reducing myocardial infarct size. Cardiovasc Drugs Ther. 2010 Apr;24(2):107-20.  [Content Brief]