EXP-3174 | CAS#124750-92-1 | AT1 antagonist

MedKoo Cat#: 522575 | Name: EXP-3174

Description:

WARNING: This product is for research use only, not for human or veterinary use.

EXP-3174, 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, EXP-3174 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.

Chemical Structure

EXP-3174

CAS#124750-92-1

Theoretical Analysis

MedKoo Cat#: 522575

Name: EXP-3174

CAS#: 124750-92-1

Chemical Formula: C22H21ClN6O2

Exact Mass: 436.1415

Molecular Weight: 436.90

Elemental Analysis: C, 60.48; H, 4.85; Cl, 8.11; N, 19.24; O, 7.32

Price and Availability

Size	Price	Availability
25mg	USD 90.00	Ready to ship
50mg	USD 150.00	Ready to ship
100mg	USD 250.00	Ready to ship
200mg	USD 450.00	Ready to ship
500mg	USD 750.00	Ready to ship
1g	USD 1,250.00	Ready to ship
2g	USD 2,150.00	Ready to ship
5g	USD 3,950.00	Ready to ship

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Synonym

EXP-3174; EXP 3174; EXP3174; E-3174; E 3174; E3174; Losartan Carboxylic Acid.

IUPAC/Chemical Name

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

InChi Key

ZEUXAIYYDDCIRX-UHFFFAOYSA-N

InChi Code

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)

SMILES Code

[H]N1N=NN=C1C2=CC=CC=C2C3=CC=C(CN4C(C(O)=O)=C(Cl)N=C4CCCC)C=C3

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C21R12B07

QC Data

View QC data: current batch, Lot#C21R12B07

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Losartan Carboxylic Acid (E-3174), an active carboxylic acid metabolite of Losartan, is an angiotensin II receptor type 1 (AT1) antagonist. The Ki values are 0.97, 0.57, 0.67 nM for rat AT1B/AT1A and human AT1, respectively.

In vitro activity:

EXP3174 and losartan abolished the angiotensin II-induced formation of inositolphosphates in VSMC. EXP3174 and losartan inhibited the angiotensin II-induced elevation of intracellular cytosolic Ca2+ concentration with an IC50 of 5 X 10(-9) and 5 X 10(-8) mol/l, respectively. EXP3174 was more effective than losartan in blocking the angiotensin II-induced increase in Egr-1 mRNA. EXP3174 and losartan inhibited the angiotensin II-induced cell protein synthesis with an IC50 of 3 X 10(-9) and 4 X 10(-8) mol/l, respectively. Reference: J Hypertens. 1993 Feb;11(2):155-62. https://pubmed.ncbi.nlm.nih.gov/8385175/

In vivo activity:

There were no significant differences between a 7- and 8-hour old thrombus in the control, VEH-treated rats (5.15 ± 1.05 mg versus 7.04 ± 1.02 mg). Administration of EXP3174 resulted in a reduction of the thrombus mass. EXP3174 significantly reduced the weight of formed thrombi to 2.40 ± 0.78 mg and 1.59 ± 0.74 mg for doses 10 and 30 mg/kg, respectively, P < 0.01 (Fig. 1). HEP, administered as a positive control, significantly reduced the weight of formed thrombi to 0.38 ± 0.08 mg, P < 0.001 (Fig. 1). Reference: J Physiol Pharmacol. 2019 Jun;70(3). https://pubmed.ncbi.nlm.nih.gov/31566190/

	Solvent	mg/mL	mM
Solubility
	DMSO	102.7	235.00
	DMF	30.0	68.67
	Ethanol	53.6	122.59
	Ethanol:PBS (pH 7.2) (1:1)	0.5	1.14

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 436.90 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Sachinidis A, Ko Y, Weisser P, Meyer zu Brickwedde MK, Düsing R, Christian R, Wieczorek AJ, Vetter H. EXP3174, a metabolite of losartan (MK 954, DuP 753) is more potent than losartan in blocking the angiotensin II-induced responses in vascular smooth muscle cells. J Hypertens. 1993 Feb;11(2):155-62. doi: 10.1097/00004872-199302000-00007. PMID: 8385175. 2. Gromotowicz-Poplawska A, Nazarko-Sadowska J, Chabielska E. Losartan metabolite EXP3174 reduces the weight of formed thrombus in 2K1C hypertensive rats. J Physiol Pharmacol. 2019 Jun;70(3). doi: 10.26402/jpp.2019.3.11. Epub 2019 Sep 27. PMID: 31566190. 3. Lynch JJ Jr, Stump GL, Wallace AA, Painter CA, Thomas JM, Kusma SE, Gould RJ, Grossman W. EXP3174, the AII antagonist human metabolite of losartan, but not losartan nor the angiotensin-converting enzyme inhibitor captopril, prevents the development of lethal ischemic ventricular arrhythmias in a canine model of recent myocardial infarction. J Am Coll Cardiol. 1999 Sep;34(3):876-84. doi: 10.1016/s0735-1097(99)00253-3. PMID: 10483973.

In vitro protocol:

In vivo protocol:

1. Gromotowicz-Poplawska A, Nazarko-Sadowska J, Chabielska E. Losartan metabolite EXP3174 reduces the weight of formed thrombus in 2K1C hypertensive rats. J Physiol Pharmacol. 2019 Jun;70(3). doi: 10.26402/jpp.2019.3.11. Epub 2019 Sep 27. PMID: 31566190. 2. Lynch JJ Jr, Stump GL, Wallace AA, Painter CA, Thomas JM, Kusma SE, Gould RJ, Grossman W. EXP3174, the AII antagonist human metabolite of losartan, but not losartan nor the angiotensin-converting enzyme inhibitor captopril, prevents the development of lethal ischemic ventricular arrhythmias in a canine model of recent myocardial infarction. J Am Coll Cardiol. 1999 Sep;34(3):876-84. doi: 10.1016/s0735-1097(99)00253-3. PMID: 10483973.

1: Choi JS, Choi JS, Choi DH. Effects of licochalcon A on the pharmacokinetics of losartan and its active metabolite, EXP-3174, 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 EXP-3174 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 EXP-3174 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. 4: Choi DH, Li C, Choi JS. Effects of myricetin, an antioxidant, on the pharmacokinetics of losartan and its active metabolite, EXP-3174, in rats: possible role of cytochrome P450 3A4, cytochrome P450 2C9 and P-glycoprotein inhibition by myricetin. J Pharm Pharmacol. 2010 Jul;62(7):908-14. doi: 10.1211/jpp.62.07.0012. PubMed PMID: 20636879. 5: Kolocouri F, Dotsikas Y, Apostolou C, Kousoulos C, Loukas YL. Simultaneous determination of losartan, EXP-3174 and hydrochlorothiazide in plasma via fully automated 96-well-format-based solid-phase extraction and liquid chromatography-negative electrospray tandem mass spectrometry. Anal Bioanal Chem. 2007 Jan;387(2):593-601. Epub 2006 Nov 21. PubMed PMID: 17119933. 6: Soldner A, Benet LZ, Mutschler E, Christians U. Active transport of the angiotensin-II antagonist losartan and its main metabolite EXP 3174 across MDCK-MDR1 and caco-2 cell monolayers. Br J Pharmacol. 2000 Mar;129(6):1235-43. PubMed PMID: 10725273; PubMed Central PMCID: PMC1571937. 7: Iwasa T, Takano T, Hara K, Kamei T. Method for the simultaneous determination of losartan and its major metabolite, EXP-3174, in human plasma by liquid chromatography-electrospray ionization tandem mass spectrometry. J Chromatogr B Biomed Sci Appl. 1999 Nov 12;734(2):325-30. PubMed PMID: 10595730. 8: Soldner A, Spahn-Langguth H, Mutschler E. HPLC assays to simultaneously determine the angiotensin-AT1 antagonist losartan as well as its main and active metabolite EXP 3174 in biological material of humans and rats. J Pharm Biomed Anal. 1998 Jan;16(5):863-73. PubMed PMID: 9535198. 9: Schwarz ER, Montino H, Fleischhauer J, Klues HG, vom Dahl J, Hanrath P. Angiotensin II receptor antagonist EXP 3174 reduces infarct size comparable with enalaprilat and augments preconditioning in the pig heart. Cardiovasc Drugs Ther. 1997 Nov;11(5):687-95. PubMed PMID: 9493708. 10: Heller J, Kramer HJ, Horácek V. Comparative effects of the angiotensin II receptor blocker EXP 3174 and of the angiotensin-converting enzyme inhibitor captopril on renal glomerular hemodynamics in the dog. Kidney Blood Press Res. 1997;20(6):391-7. PubMed PMID: 9453450. 11: Heller J, Horácek V. Effect of PD 123319, an AT-2 antagonist, on renal function of the anesthetized dog: comparison with EXP 3174, an AT-1 blocker. Kidney Blood Press Res. 1997;20(5):297-301. PubMed PMID: 9419044. 12: Li XC, Widdop RE. Angiotensin type 1 receptor antagonists CV-11974 and EXP 3174 cause selective renal vasodilatation in conscious spontaneously hypertensive rats. Clin Sci (Lond). 1996 Aug;91(2):147-54. PubMed PMID: 8795437. 13: Basso N, Kurnjek ML, Ruiz P, Cannata MA. Effect of EXP 3174 on blood pressure of normoreninemic renal hypertensive rats. Hypertension. 1995 Feb;25(2):283-7. PubMed PMID: 7843780. 14: Bartholomeusz B, Widdop RE. Effect of acute and chronic treatment with the angiotensin II subtype 1 receptor antagonist EXP 3174 on baroreflex function in conscious spontaneously hypertensive rats. J Hypertens. 1995 Feb;13(2):219-25. PubMed PMID: 7615952. 15: Widdop RE, Gardiner SM, Kemp PA, Bennett T. Comparison of the regional haemodynamic effects of the AT1-receptor antagonists, losartan and EXP 3174, in water-deprived Brattleboro rats. Br J Pharmacol. 1993 Mar;108(3):684-8. PubMed PMID: 8467356; PubMed Central PMCID: PMC1908057. 16: Osei SY, Minkes RK, Bellan JA, Kadowitz PJ. Analysis of the inhibitory effects of DuP 753 and EXP 3174 on responses to angiotensin II in the feline hindquarters vascular bed. J Pharmacol Exp Ther. 1993 Mar;264(3):1104-12. PubMed PMID: 8450454. 17: Widdop RE, Gardiner SM, Kemp PA, Bennett T. Central administration of PD 123319 or EXP-3174 inhibits effects of angiotensin II. Am J Physiol. 1993 Jan;264(1 Pt 2):H117-25. PubMed PMID: 7679256. 18: Widdop RE, Gardiner SM, Kemp PA, Bennett T. Inhibition of the haemodynamic effects of angiotensin II in conscious rats by AT2-receptor antagonists given after the AT1-receptor antagonist, EXP 3174. Br J Pharmacol. 1992 Nov;107(3):873-80. PubMed PMID: 1472980; PubMed Central PMCID: PMC1907755.