U 46619
EC50: 0.035 μM for shape change, 0.057 μM for MLCP, 0.536 μM for serotonin release, 1.31 μM for aggregation and 0.53 μM for fibrinogen receptor binding [3].
Prostaglandin endoperoxide analogue U46619 (11,9 epoxymethano-prostaglandin H2) is a selective agonist of prostaglandin H2 (PGH2)/thromboxane A2 (TxA2) (TP) receptor. Both PGH2 and TxA2 receptors are G-protein coupled receptors.
In vitro: U46619 showed a biphasic effect on human platelets. Shape change and MLCP occurred at low concentrations of this compound (EC50 = 0.035 uM and 0.057 uM), whereas serotonin release, platelet at higher concentrations (EC50 = 0.536 uM and 1.31 uM). The effect on platelet shape change and MLCP is receptor mediated [3].
In vivo: U46619, through activation of ETA and ETB receptors, elicits renal cortical vasoconstriction and medullary vasodilation in the rat [2]. In conscious SHR (spontaneously hypertensive rats), 1-100 nmol/kg U-46619 (i.c.v.) induced a dose-related increase in blood pressure but had no significant effect on heart rate [1].
Clinical trial: So far, no clinical study has been conducted.
References:
[1] Sirén AL, Svartstrm-Fraser M, Paakkari I.? Central cardiovascular effects of the endoperoxide analogue U-46619 in rats. Prostaglandins Leukot Med. 1985 Mar; 17 (3): 381-6.
[2] Hantz H, Adesuyi A, Adebayo O.? Differential effects of U46619 on renal regional hemodynamics in the rat: involvement of endothelin. J Pharmacol Exp Ther. 2001 Oct; 299 (1): 372-6.
[3] Morinelli TA1, Niewiarowski S, Daniel JL, Smith JB.? Receptor-mediated effects of a PGH2 analogue (U 46619) on human platelets. Am J Physiol. 1987 Nov; 253 (5 Pt 2): H1035-43.
- 1. Xi Chen, Xin Chen, et al. "GV-971 prevents severe acute pancreatitis by remodeling the microbiota-metabolic-immune axis." Nat Commun. 2024 Sep 27;15(1):8278 PMID: 39333064
- 2. Zhixiang Zhu, Yanggan Luo, et al. "Icaritin Sensitizes Thrombin-and TxA2-Induced Platelet Activation and Promotes Hemostasis via Enhancing PLCγ2-PKC Signaling Pathways." Thromb Haemost. 2024 Feb 9. PMID: 38224965
- 3. Cheng Wei, Jishou Zhang, et al. "Resolvin D1 attenuates Ang II-induced hypertension in mice by inhibiting the proliferation, migration and phenotypic transformation of vascular smooth muscle cells by blocking the RhoA/mitogen-activated protein kinase pathway." J Hypertens. 2023 Nov 7. PMID: 37937508
- 4. JQingfeng Yu, Chengjie Wu, et al. "Inhibition of LIM kinase reduces contraction and proliferation in bladder smooth muscle." Acta Pharm Sin B. 2021 Jul;11(7):1914-1930. PMID:34386328
- 5. Fengyang Li, Dan Xu, et al. "Pretreatment of Indobufen and Aspirin and their Combinations with Clopidogrel or Ticagrelor Alleviates Inflammasome Mediated Pyroptosis Via Inhibiting NF-κB/NLRP3 Pathway in Ischemic Stroke." J Neuroimmune Pharmacol. 2021 Dec;16(4):835-853. PMID:33512659
- 6. Xu Li, Gaoqing Xu, et al. "Gonadotropin-inhibiting hormone promotes apoptosis of bovine ovary granulosa cells." Life Sci. 2021 Apr 1;270:119063. PMID:33460664
- 7. Xiao J, Wang F, et al. "Targeting the COX2/MET/TOPK signaling axis induces apoptosis in gefitinib-resistant NSCLC cells." Cell Death Dis. 2019 Oct 14;10(10):777. PMID:31611604
- 8. Luo Y, Teng X, et al. "CD146-HIF-1α hypoxic reprogramming drives vascular remodeling and pulmonary arterial hypertension." Nat Commun. 2019 Aug 7;10(1):3551. PMID:31391533
- 9. Yan YY, Ao LY, et al. "Therapeutic effects of JLX001 on cerebral ischemia through inhibiting platelet activation and thrombus formation in rats." Biomed Pharmacother. 2018 Jul 7;106:805-812. PMID:29990874
- 10. Zhang Q, Tan C, et al. "Characterization of active antiplatelet chemical compositions of edible Citrus limon through ultra-performance liquid chromatography single quadrupole mass spectrometry-based chemometrics." Food Funct. 2018 Apr 24.
- 11. Zhang Q, Tan CN, et al. "Adsorbed hollow fiber-based biological fingerprinting for the discovery of platelet aggregation inhibitors from Danshen-Honghua decoction." J Sep Sci. 2018 Mar 23. PMID:29573136
| Physical Appearance | A solution in methyl acetate, learn about Variance in Solubility |
| Storage | Store at -20°C |
| M.Wt | 350.5 |
| Cas No. | 56985-40-1 |
| Formula | C21H34O4 |
| Solubility | ≥100 mg/mL in DMSO, ≥100 mg/mL in Ethanol, ≥100 mg/mL in DMF, ≥2 mg/mL in PBS pH 7.2 |
| Chemical Name | (E)-7-((1R,4R,5S,6R)-6-((S,Z)-3-hydroxyoct-1-en-1-yl)-2-oxabicyclo[2.2.1]heptan-5-yl)hept-5-enoic acid |
| SDF | Download SDF |
| Canonical SMILES | O[C@@H](CCCCC)/C=C\[C@@H]1[C@@H](C/C=C/CCCC(O)=O)[C@H]2C[C@H]1OC2 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
|
Cell lines |
Human platelet |
|
Preparation method |
Soluble in methyl acetate (supplied pre-dissolved -10 mg/mL). General tips for obtaining a higher concentration: Please warm the tube at 37°C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months. |
|
Reacting condition |
24 h |
|
Applications |
In human platelet, U 46619 induced serotonin release, platelet aggregation, and fibrinogen receptor with the EC50 values of 0.54 ± 0.13, 1.31 ± 0.34 and 0.53 ± 0.21 μM, respectively. |
| Animal experiment [2]: | |
|
Animal models |
Conscious spontaneously hypertensive rats (SHR) |
|
Dosage form |
Intracerebroventricular (ICV) administration, 1-100 nmol/kg |
|
Application |
In conscious spontaneously hypertensive rats (SHR), U-46619 (1–100 nmol/kg i.c.v.) induced a strong dose-related increase in blood pressure but had no significant effect on heart rate. In conscious noruotensive rats (NR) neither blood pressure nor heart rate was significantly affected. Furthermore, U-46619 (0.1-100 nmol/kg, i.c.v.) had no significant effect on blood pressure, heart rate or ventilation in urethane-anaesthetised NR . |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
References: [1] Morinelli T A, Niewiarowski S, Daniel J L, et al. Receptor-mediated effects of a PGH2 analogue (U 46619) on human platelets [J]. American Journal of Physiology-Heart and Circulatory Physiology, 1987, 253 (5): H1035-H1043. [2] Siren A L, Svartstrm-Fraser M, Paakkari I. Central cardiovascular effects of the endoperoxide analogue U-46619 in rats [J]. Prostaglandins, Leukotrienes and Medicine, 1985, 17 (3): 381-386. |
|
Quality Control & MSDS
- View current batch:
-
Purity = 98.00%
- COA (Certificate Of Analysis)
- MSDS (Material Safety Data Sheet)
- Datasheet
Chemical structure
Related Biological Data
Related Biological Data
Related Biological Data
Related Biological Data
Related Biological Data
Related Biological Data
Related Biological Data
