tcsc2116 Losartan

Losartan is an angiotensin II receptor antagonist, competing with the binding of angiotensin II to AT1 receptors with IC₅₀ of 20 nM.

IC50 & Target: IC50: 20 nM (angiotensin II)

In Vitro: 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^[1]. Losartan (40 μM) affects I_SC but prevents the effect of ANGII on I_SC^[2]. 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^[3].

In Vivo: 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^[4]. 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^[5].