EXP3174

EXP3174, also known as Losartan Carboxylic Acid, is a physiologically active metabolite of losartan, produced by cytochrome P450 isoforms in the liver. Like the parent compound, EXP3174 is a potent AT1 antagonist (Kis = 0.57 and 0.67 nM for rat and human forms, respectively), producing a depressor response and vasodilatation. When administered intravenously, losartan carboxylic acid is more potent and has a longer duration of action than losartan. However, the metabolite has very low oral bioavailability.

Product information

CAS Number: 124750-92-1

Molecular Weight: 436.89

Formula: C22H21ClN6O2

Synonym:

EXP-3174

E-3174

Losartan Carboxylic Acid

EXP 3174

EXP3174

E 3174

E3174

Chemical Name: 1-((2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-2-butyl-4-chloro-1H-imidazole-5-carboxylic acid

Smiles: CCCCC1=NC(Cl)=C(C(O)=O)N1CC1C=CC(=CC=1)C1=CC=CC=C1C1NN=NN=1

InChiKey: ZEUXAIYYDDCIRX-UHFFFAOYSA-N

InChi: InChI=1S/C22H21ClN6O2/c1-2-3-8-18-24-20(23)19(22(30)31)29(18)13-14-9-11-15(12-10-14)16-6-4-5-7-17(16)21-25-27-28-26-21/h4-7,9-12H,2-3,8,13H2,1H3,(H,30,31)(H,25,26,27,28)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

The specific binding of [125I]-angiotensin II to VSMC is inhibited by EXP3174 with an IC50 of 1.1 nM. Losartan Carboxylic Acid abolishes the angiotensin II-induced formation of inositolphosphates in VSMC. EXP3174 inhibits the angiotensin II-induced elevation of intracellular cytosolic Ca2+ concentration with an IC50 of 5 nM. EXP3174 is more effective than losartan in blocking the angiotensin II-induced increase in Egr-1 mRNA. EXP3174 inhibits the angiotensin II-induced cell protein synthesis with an IC50 of 3 nM.

In Vivo:

EXP3174 (0.1 mg/kg; i.v. followed by 0.02 mg/kg/h for 5.5 h) induces a similar level of inhibition (87±4%) of the pressor responses to angiotensin I. Intravenous EXP3174 (0.1 mg/kg+0.01 mg/kg/min) is infused in anesthetized dogs with recent (8.1±0.4 days) anterior myocardial infarction. Electrolytic injury of the left circumflex coronary artery to induce thrombotic occlusion and posterolateral ischemia is initiated 1 h after the start of treatment.

References:

1. Choi JS, Choi JS, Choi DH. Effects of licochalcon A on the pharmacokinetics of losartan and its active metabolite,EXP3174, in rats. Pharmazie. 2013 Nov;68(11):882-8. PubMed PMID: 24380237.
2. Yang SH, Choi JS, Choi DH. Effects of HMG-CoA reductase inhibitors on the pharmacokinetics of losartan and its main metabolite EXP3174 in rats: possible role of CYP3A4 and P-gp inhibition by HMG-CoA reductase inhibitors. Pharmacology. 2011;88(1-2):1-9. doi: 10.1159/000328773. Epub 2011 Jun 25. PubMed PMID: 21709429.
3. Yang SH, Cho YA, Choi JS. Effects of ticlopidine on pharmacokinetics of losartan and its main metabolite EXP3174 in rats. Acta Pharmacol Sin. 2011 Jul;32(7):967-72. doi: 10.1038/aps.2011.32. Epub 2011 Jun 13. PubMed PMID: 21666702; PubMed Central PMCID: PMC4003123.

Products are for research use only. Not for human use.