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Losartan Potassium (DuP 753)

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InvivoChem Cat #: V1773

CAS #: 124750-99-8Purity ≥98%

Description: Losartan Potassium (formerly DuP-753; MK-954; DuP753; MK954; Cozaar; Lorzaar; Losaprex), the potassium salt of losartan, is an oral, selective, and non-peptide angiotensin II receptor antagonist approved as an antihypertensive drug. It is an AT II antagonist that competes with angiotensin II for binding to AT1 receptors with IC50 of 20 nM.

References: Circulation. 2001 Feb 13;103(6):904-12; Circulation. 2000 Apr 4;101(13):1586-93.

Related CAS #: 124750-99-8 (Ka+) 114798-26-4 (free)

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Molecular Weight (MW)	462.01
Formula	C22H23ClKN6O
CAS No.	124750-99-8
Storage	-20℃ for 3 years in powder form
Storage	-80℃ for 2 years in solvent
Solubility (In vitro)	DMSO: 92 mg/mL (199.1 mM)
	Water: 92 mg/mL (199.1 mM)
	Ethanol: 92 mg/mL (199.1 mM)
Solubility (In vivo)	Saline: 30 mg/mL
Synonyms	DuP 753; MK 954; DuP-753; MK-954; DuP753; MK954; Cozaar; Lorzaar; Losaprex; UNII-3ST302B24A; MK954;

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In Vitro	In vitro activity: 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. Losartan (40 μM) affects ISC but prevents the effect of ANGII on ISC. 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. Cell Assay: An MTT assay is used to measure cell proliferation and viability. For the assay, 5000 cells in 200 μL media per well are seeded in a 96 well plate. After overnight incubation to allow for cell attachment, the medium is removed by suction. MTT at 1 mg/mL concentration in serum-free medium is added and then incubated for 4 h at 37°C. After removal of MTT solution, 100 μL of DMSO is added to dissolve formazan crystals. Absorbance at 570 nm and at 600 nm as a reference is then measured using a microplate reader. The difference in absorbance is thus relative to the extent of cell survival.
In Vivo	Losartan (180 mg/d) causes significant increases in plasma angiotensin II and angiotensin-(1-7) in monkeys with diet-induced hypercholesterolemia. Losartan (180 mg/d) reduces the extent of fatty streak in the aorta, the coronary arteries, and the carotid arteries by approximately 50% in monkeys with diet-induced hypercholesterolemia. Losartan reduces the susceptibility of LDL to in vitro oxidation, serum levels of monocyte chemoattractant protein-1, and circulating monocyte CD11b expression in monkeys with diet-induced hypercholesterolemia. Losartan (0.6 g/L in their drinking water) prevents elastic fiber fragmentation and blunted TGF-β signaling in the aortic media in pregnant Fbn1C1039G/+ mice, as evidenced by reduced nuclear accumulation of pSmad2. Losartan (0.6 g/L in their drinking water) shows a reduction in distal airspace caliber in pregnant Fbn1C1039G/+ mice. Losartan (0.6 g/L in their drinking water) improves disease manifestations in the lungs, an event that cannot plausibly relate to improved hemodynamics in pregnant Fbn1C1039G/+ mice. Losartan (5 mg/kg/d) leads to a significant decrease in the development of atherosclerotic lesions in the apo E deficient mice. Losartan (5 mg/kg/d) significantly reduces the susceptibility of the mice LDL to lipid oxidation following its incubation with CuSO4 in the apo E deficient mice. Losartan (10 mg/kg) administration increases blood angiotensin levels four fold to six fold, blood BK levels are unchanged in male Sprague Dawley rats. Losartan (10 mg/kg) increases plasma renin levels 100-fold, plasma angiotensinogen levels decreases to 24% of control and plasma aldosterone levels are unchanged in male Sprague Dawley rats.
Animal model	Male cynomolgus monkeys fed a diet containing 0.067 mg cholesterol/kJ
Formulation & Dosage	Dissolved in 50% dimethylsulfoxide/50% distilled water; 180 mg/d; Taken via diet
References	Circulation. 2001 Feb 13;103(6):904-12; Circulation. 2000 Apr 4;101(13):1586-93.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Lot#: V177301,Purity ≥98%
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