U-46619

Names

[ Name ]:
U-46619

[Synonym ]:
5-Heptenoic acid, 7-[(1R,4S,5S,6R)-6-[(1E,3S)-3-hydroxy-1-octen-1-yl]-2-oxabicyclo[2.2.1]hept-5-yl]-, (5Z)-
(5Z)-7-{(1R,4S,5S,6R)-6-[(1E,3S)-3-Hydroxy-1-octen-1-yl]-2-oxabicyclo[2.2.1]hept-5-yl}-5-heptenoic acid
MFCD00135238
U 46619,(5Z)-7-[(1R,4S,5S,6R)-6-[(1E,3S)-3-Hydroxy-1-octenyl]-2-oxabicyclo[2.2.1]hept-5-yl]-5-heptenoicacid

Biological Activity

[Description]:

U-46619 (9,11-Methanoepoxy PGH2) is a stable analogue of thromboxane A2 (TXA2) and acts as a potent TXA2 agonist[1].

[Related Catalog]:

Research Areas >> Cardiovascular Disease

Signaling Pathways >> GPCR/G Protein >> Prostaglandin Receptor

[Target]

TXA2[1]

[In Vitro]

U-46619 (1 nM-10 μM) causes platelets shape change and aggregation in a concentration-dependent manner, and with EC50s of 0.58 μM and 0.013 μM for aggregation and shape change, respectively[1]. U-46619 (10 nM-10 μM) increases internal Ca2+ concentration ([Ca2+]i) and activates phosphoinositide (PI) hydrolysis in a concentration-dependent manner with a similar concentration-dependency[1]. U-46619 (3 nM-10 μM) also activates GTPase concentration-dependently in the membranes derived from platelets[1]. U-46619 improves the differentiation efficiency of human induced pluripotent stem cells into endothelial cells by activating both p38MAPK and ERK1/2 signaling pathways[2].

[In Vivo]

U-46619 (5 μg/kg; i.v.) increases blood pressure in male spontaneously hypertensive rats (SHR)[3]. Animal Model: 12-15 weeks-old male and female SHR[2] Dosage: 5 μg/kg Administration: Intravenous injection Result: Induceed a significant increase of MABP after 1 min in male SHR.

[References]

[1]. Ohkubo S, et al. Thromboxane A2-mediated shape change: independent of Gq-phospholipase C--Ca2+ pathway in rabbit platelets. Br J Pharmacol. 1996 Mar;117(6):1095-104.

[2]. Su L, et al. The prostaglandin H2 analog U-46619 improves the differentiation efficiency of human induced pluripotent stem cells into endothelial cells by activating both p38MAPK and ERK1/2 signaling pathways. Stem Cell Res Ther. 2018 Nov 15;9(1):313.

[3]. Schirner M, et al. U 46619 induces different blood pressure effects in male and female spontaneously hypertensive rats (SHR). Prostaglandins Leukot Essent Fatty Acids. 1993 Jun;48(6):469-73.

Chemical & Physical Properties

[ Density]:
1.1±0.1 g/cm3

[ Boiling Point ]:
519.7±30.0 °C at 760 mmHg

[ Molecular Formula ]:
C₂₁H₃₄O₄

[ Molecular Weight ]:
350.492

[ Flash Point ]:
176.1±18.1 °C

[ Exact Mass ]:
350.245697

[ PSA ]:
66.76000

[ LogP ]:
3.90

[ Vapour Pressure ]:
0.0±3.1 mmHg at 25°C

[ Index of Refraction ]:
1.548

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: MJ9681090

CHEMICAL NAME :: 5-Heptenoic acid, 7-(6-(3-hydroxy-1-octenyl)-2-oxabicyclo(2.2.1)hept-5- yl)-, (1R-(1-alpha, 4-alpha,5-beta(Z),6-alpha(1E,3S*)))-

CAS REGISTRY NUMBER :: 56985-40-1

LAST UPDATED :: 198306

DATA ITEMS CITED :: 1

MOLECULAR FORMULA :: C21-H34-O4

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 66 ug/kg

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - dyspnea Lungs, Thorax, or Respiration - other changes

REFERENCE :: JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 224,369,1983

Safety Information

[ Symbol ]:

GHS02, GHS07

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H225-H319-H336

[ Supplemental HS ]:
Repeated exposure may cause skin dryness or cracking.

[ Precautionary Statements ]:
P210-P280-P304 + P340 + P312-P305 + P351 + P338-P337 + P313-P403 + P235

[ Personal Protective Equipment ]:
Eyeshields;Faceshields;full-face respirator (US);Gloves;multi-purpose combination respirator cartridge (US);type ABEK (EN14387) respirator filter

[ Hazard Codes ]:
F;Xi

[ Risk Phrases ]:
R11;R36;R66;R67

[ Safety Phrases ]:
S16;S26

[ RIDADR ]:
UN 1231 3/PG 2

Articles

P2X1-initiated p38 signalling enhances thromboxane A2-induced platelet secretion and aggregation.

Thromb. Haemost. 112(1) , 142-50, (2014)

ATP released by activated platelets can serve as a positive feedback machinery to amplify platelet responses by activating P2X1 receptors. It has, however, not been defined how P2X1 activities influen...

Thromboxane A(2) receptor stimulation promotes closure of the rat ductus arteriosus through enhancing neointima formation.

PLoS ONE 9(4) , e94895, (2014)

Ductus arteriosus (DA) closure follows constriction and remodeling of the entire vessel wall. Patent ductus arteriosus occurs when the DA does not close after birth, and this condition is currently tr...

A platelet P-selectin test predicts adverse cardiovascular events in patients with acute coronary syndromes treated with aspirin and clopidogrel.

Platelets 25(8) , 612-8, (2014)

There is wide variation in response to antiplatelet therapy and high on-treatment platelet reactivity is associated with adverse cardiovascular events. The objective here was to determine whether the ...