Losartan-d₆ hydrochloride  (Synonyms: DuP-753-d₆ hydrochloride)

Losartan-d₆ hydrochloride is deuterated labeled Losartan potassium (HY-17512A). Losartan potassium (DuP-753 potassium) is an angiotensin II receptor type 1 (AT1) antagonist, competing with the binding of angiotensin II to AT1 with an IC₅₀ of 20 nM.

Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs^[1].
Losartan competes with the binding of angiotensin II to AT1 receptors. The concentration that inhibits 50% of the binding of angiotensin II (IC₅₀) is 20 nM^[2]. Losartan (40 μM) affects I_SC but prevents the effect of ANGII on I_SC^[3]. Losartan significantly reduces Ang II-mediated cell proliferation in endometrial cancer cells. The combination of losartan and anti-miR-155 has a significantly greater antiproliferative effect compared to each drug alone^[4].

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

Losartan (0.6 g/L, p.o.) -treated Fbn1^C1039G/+ mice show a reduction in distal airspace caliber relative to placebo-treated Fbn1^C1039G/+ animals. The doses of losartan and propranolol are titrated to achieve comparable hemodynamic effects. Analysis of pSmad2 nuclear staining reveals that losartan antagonizes TGF-β signaling in the aortic wall of Fbn1^C1039G/+ mice. Losartan can improve disease manifestations in the lungs, an event that cannot plausibly relate to improved hemodynamics^[5]. Losartan (10 mg/kg, intraarterial injection) increases blood angiotensin levels four- to sixfold. Losartan (10 mg/kg, i.p.) increases plasma renin levels 100-fold; plasma angiotensinogen levels decreases to 24% of control; and plasma aldosterone levels are unchanged^[6].

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

465.41

C₂₂H₁₈D₆Cl₂N₆O

124750-99-8

OCC1=C(Cl)N=C(CCCC)N1C([2H])([2H])C2=CC=C(C3=C([2H])C([2H])=C([2H])C([2H])=C3C4=NNN=N4)C=C2.Cl

Room temperature in continental US; may vary elsewhere.

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

• [1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-216.  [Content Brief]

  [2]. Burnier, M. Angiotensin II type 1 receptor blockers. Circulation, 2001. 103(6): p. 904-12.  [Content Brief]

  [3]. Choi, C.H., et al. Angiotensin II type I receptor and miR-155 in endometrial cancers: synergistic antiproliferative effects of anti-miR-155 and losartan on endometrial cancer cells. Gynecol Oncol, 2012. 126(1): p. 124-31.  [Content Brief]

  [4]. Habashi, J.P., et al. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science, 2006. 312(5770): p. 117-21.  [Content Brief]

  [5]. Ashry, O., et al. Evidence for expression and function of angiotensin II receptor type 1 in pulmonary epithelial cells. Respir Physiol Neurobiol, 2014.  [Content Brief]

  [6]. Campbell, D.J., et al. Effects of losartan on angiotensin and bradykinin peptides and angiotensin-converting enzyme. J Cardiovasc Pharmacol, 1995. 26(2): p. 233-40.  [Content Brief]