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25mg |
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Purity: ≥98%
Treprostinil (LRX-15; trade names: Remodulin for infusion, Orenitram for oral, and Tyvaso for inhalation), a synthetic analog of prostacyclin (PGI2), is a novel and potent DP1 and EP2 agonist with EC50 values of 0.6±0.1 and 6.2±1.2 nM, respectively. Treprostinil is a vasodilator that is applied to the management of hypertension in the lungs. The FDA approved treprostinil inhalation form in July 2009; it is sold under the trade name Tyvaso.
Targets |
IP Receptor ( EC50 = 1.9 nM ); TP Receptor ( EC50 = 919 nM ); IP Receptor ( Ki = 32.1 nM ); IP Receptor ( Ki = 4680 nM )
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ln Vitro |
Treprostinil exhibits low affinity for EP1 and EP4 receptors, even lower affinity for EP3, FP, and TP receptors, and high affinity for DP1, EP2, and IP receptors (Ki=4.4, 3.6, and 32 nM, respectively). Similar to treprostinil, activation of IP, DP1, and EP2 receptors can all cause the human pulmonary arteries to vasodilate[1]. The viability of cultured endothelial colony-forming cells is inhibited by treprostinil. The proliferation of endothelial colony forming cells is induced by conditioned media derived from mesenchymal stem cells that have been treated with treprostinil[5].
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ln Vivo |
The most recent medication to be approved by the FDA to treat pulmonary arterial hypertension (PAH), a deadly orphan disease, is inhaled treprostinil sodium, a prostacyclin analog[2]. Compared to a placebo, treprostinil lessens platelet deposition early after transplantation and maintains the sinusoidal endothelial cell lining. The treprostinil group maintains blood flow close to normal levels, while the placebo group's hepatic tissue blood flow is significantly reduced[3]. The ability of mesenchymal stem cells and endothelial colony-forming cells to form vessels in Matrigel implanted in nude mice is greatly enhanced by treprostinil treatment. Treprostinil's pro-angiogenic effect is also inhibited by silencing the VEGF-A gene in mesenchymal stem cells[4]. Hematopoietic stem and progenitor cells from mice and humans respond best to treprostinil when it comes to increasing intracellular cAMP levels[5]. When compared to normoxic mice, treatment with Treprostinil significantly reduces the recruitment of cells. Treprostinil fails to reverse right ventricular hypertrophy, but it does lower right ventricular systolic pressure and slightly lessen vascular remodelling[6].
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Cell Assay |
Hematopoietic stem and progenitor cells from humans or mice are cultured for one hour and twenty-four hours at 37°C either in the presence of vehicle or in combination with 10 μM Treprostinil and 30 μM forskolin. The apoptosis kit is used to stain cells for externalized phosphatidylserine after they have been washed with phosphate-buffered saline at 4°C[5].
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Animal Protocol |
Rats: For the study, male Lewis rats weighing between 200 and 300 g are employed. 24 hours prior to hepatectomy, donor animals are given treprostinil or a placebo, and the corresponding recipient animal receives the same care until the moment of sacrifice. Treatment is invisible to the surgeon. To study what happens right after IRI, recipients are sacrificed 1, 3, 6, 24 and 48 hours after transplantation. Using an Alzet implantable osmotic pump, subcutaneous administration of treprostinil (100 ng/kg/min) or placebo is performed. This dosage is chosen to produce a plasma concentration that is steady-state and falls between 5 and 20 ng/mL[3].
Mice: Mice that have had bone marrow transplantation (BMT) are split up into five groups, each with six to ten mice. In a normobaric chamber, one group of mice is exposed to hypoxia (10% inspired oxygen fraction), while the other group of mice (control BMT) spends 28 days in a normoxic chamber with a normal oxygen environment (21% inspired O2 fraction). While the two other groups of mice receive four weeks of hypoxic exposure and receive Treprostinil infusions at varying dose levels (14 ng/kg and 70 ng/kg per minute), the sham group mice receive saline treatment. Comparatively, infusion rates for humans in PAH therapy range from 10 to 60 ng/kg per minute[6]. |
References |
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Molecular Formula |
C23H34O5
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Molecular Weight |
412.49500
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Exact Mass |
390.24
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Elemental Analysis |
C, 70.74; H, 8.78; O, 20.48
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CAS # |
81846-19-7
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Related CAS # |
Treprostinil sodium; 289480-64-4; Treprostinil-13C2,d; Treprostinil-d9; 2747918-14-3; Treprostinil diethanolamine; 830354-48-8
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Appearance |
Oily liquid
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SMILES |
CCCCC[C@@H](CC[C@H]1[C@@H](C[C@H]2[C@@H]1CC3=C(C2)C(=CC=C3)OCC(=O)O)O)O
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InChi Key |
PAJMKGZZBBTTOY-ZFORQUDYSA-N
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InChi Code |
InChI=1S/C23H34O5/c1-2-3-4-7-17(24)9-10-18-19-11-15-6-5-8-22(28-14-23(26)27)20(15)12-16(19)13-21(18)25/h5-6,8,16-19,21,24-25H,2-4,7,9-14H2,1H3,(H,26,27)/t16-,17-,18+,19-,21+/m0/s1
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Chemical Name |
2-[[(1R,2R,3aS,9aS)-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[g]naphthalen-5-yl]oxy]acetic acid
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Synonyms |
LRX15; LRX 15; LRX-15; UT15; UT-15; UT 15; BW 15AU; Uniprost; TU-62840; reprostinil; Orenitram; Remodulin
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
DMSO: ≥ 125 mg/mL (~320.1 mM)
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.33 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.33 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (5.33 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.4242 mL | 12.1212 mL | 24.2424 mL | |
5 mM | 0.4848 mL | 2.4242 mL | 4.8485 mL | |
10 mM | 0.2424 mL | 1.2121 mL | 2.4242 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT03045029 | Active Recruiting |
Drug: Oral treprostinil | Pulmonary Arterial Hypertension | United Therapeutics | July 18, 2017 | N/A |
NCT05176951 | Active Recruiting |
Drug: Treprostinil Palmitil Drug: Placebo |
Pulmonary Hypertension | Insmed Incorporated | December 22, 2022 | Phase 2 |
NCT05060315 | Active Recruiting |
Combination Product: Remunity Pump for Remodulin |
Pulmonary Arterial Hypertension | United Therapeutics | July 5, 2023 | N/A |
NCT03835676 | Recruiting | Drug: Treprostinil | Pulmonary Hypertension | Magdi H. Yacoub | May 1, 2019 | Phase 4 |
NCT04005469 | Recruiting | Drug: Treprostinil | Ischemia Reperfusion Injury Delayed Graft Function |
Rhode Island Hospital | November 13, 2020 | Phase 1 Phase 2 |
Vascular remodelling (20–70 μm vessel diameter) was partially reversed with treprostinil treatment. Eur Respir J . 2010 Dec;36(6):1302-14. td> |
In vivo recruitment of circulating fibrocytes to the perivascular area in response to hypoxia is inhibited by treprostinil infusion. a) The number of recruited collagen (Col)1+/GFP+ cells increased in response to chronic hypoxia compared to normoxic mice. Eur Respir J . 2010 Dec;36(6):1302-14. td> |
Comparison of hepatic IRI in placebo- and treprostinil-treated animals. Am J Transplant . 2011 Nov;11(11):2508-16. td> |
Pretreatment of murine and human HSPCs with treprostinil and forskolin does neither induce apoptosis nor alters cell cycle progression or differentiation potential. Mol Pharmacol . 2016 Jun;89(6):630-44. td> |
Treprostinil increases in vivo vasculogenic potential of ECFC and MSC combination. Thromb Haemost . 2015 Oct;114(4):735-47. td> |