Home GPCR & G Protein Angiotensin Receptor antagonist Losartan Carboxylic Acid (EXP-3174) For research use only.

Losartan Carboxylic Acid (EXP-3174)

Synonyms: E-3174

Losartan Carboxylic Acid (E-3174, EXP-3174), an active carboxylic acid metabolite of Losartan, is a non-peptide angiotensin II (AT1) receptor antagonist. Losartan Carboxylic Acid inhibits the specific binding of [125I]-angiotensin II to VSMC with IC50 of 1.1 nM.

Losartan Carboxylic Acid (EXP-3174) Chemical Structure

Losartan Carboxylic Acid (EXP-3174) Chemical Structure

CAS No. 124750-92-1

Purity & Quality Control

Batch: S598001 DMSO]87 mg/mL]false]Ethanol]87 mg/mL]false]Water]Insoluble]false Purity: 99.41%
99.41

Losartan Carboxylic Acid (EXP-3174) Related Products

Biological Activity

Description Losartan Carboxylic Acid (E-3174, EXP-3174), an active carboxylic acid metabolite of Losartan, is a non-peptide angiotensin II (AT1) receptor antagonist. Losartan Carboxylic Acid inhibits the specific binding of [125I]-angiotensin II to VSMC with IC50 of 1.1 nM.
Targets
binding of [125I]-angiotensin II to VSMC [1]
(Cell-free assay)
1.1 nM
In vitro
In vitro

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 nmol/L[2]. Losartan increases AMPK phosphorylation in a time- and dose-dependent manner in VSMCs. It also increases ACC phosphorylation, a major downstream target protein in the AMPK signaling cascade, and LKB1 phosphorylation, which is an upstream kinase of AMPK. Losartan increases p53 and p21 expression in a time-dependent manner, whereas the levels of p27 are not changed. Losartan suppresses Ang II-induced Rb phosphorylation, as well as cyclin D and cyclin E expression which are required for cell cycle progression. The mechanism of growth suppression by losartan is therefore G0/G1 cell cycle arrest which is reversed by AMPK inhibition, such as compound C or AMPK siRNA, but not by apoptosis[3].
Cell Research Cell lines VSMCs
Concentrations 0, 1, 5, 10 μM
Incubation Time 48 h
Method

Cells were treated with Ang II or 15% FBS in the presence or absence of indicated concentration of losartan for 48 hrs. Cell proliferation was determined by the MTT assay.
In Vivo
In vivo

Losartan has a major active metabolite, EXP 3174. Administered intravenously, EXP3174 is 10 to 20 times more potent than losartan and has a longer duration of action than losartan. However, the oral bioavailability of EXP 3174 is very low. Losartan has a bioavailability of about 33%, the half-life averages 2 h (6-9 hours), and the rate of protein binding is 98.7% when dosed at 50-100 mg/d[2]. Treatment with losartan ameliorates the loss in the number and function of endothelial progenitor cells (EPCs) in hypertensive rats[4].
Animal Research Animal Models 12-week-old male Wistar-Kyoto (WKY) rats and SHR-SP
Dosages 10 mg/kg/day
Administration oral
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT05407220 Unknown status
Healthy
Hanmi Pharmaceutical Company Limited
 June 8 2022 Phase 1
NCT05191563 Completed
Healthy
Hanmi Pharmaceutical Company Limited
 July 31 2021 Phase 1
NCT04322266 Completed
Healthy
Hanmi Pharmaceutical Company Limited
 December 21 2018 Phase 1
NCT04081844 Completed
Healthy
Hanmi Pharmaceutical Company Limited
 May 3 2018 Phase 1

Chemical Information & Solubility

Molecular Weight 436.89 Formula

C22H21ClN6O2
CAS No. 124750-92-1 SDF --
Smiles CCCCC1=NC(=C([N]1CC2=CC=C(C=C2)C3=CC=CC=C3C4=N[NH]N=N4)C(O)=O)Cl
Storage (From the date of receipt) 3 years -20°C powder

In vitro
Batch:

DMSO : 87 mg/mL ( (199.13 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 87 mg/mL

Water : Insoluble


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