IP Receptor ( EC50 = 1.9 nM ); TP Receptor ( EC50 = 919 nM ); IP Receptor ( Ki = 32.1 nM ); IP Receptor ( Ki = 4680 nM );
DP/DP1 Receptor:0.6 nM (EC50); IP Receptor:1.9 nM (EC50); EP2 Receptor:6.2 nM (EC50) ; EP3 Receptor:68.9 nM (EC50) ; EP4 Receptor:181 nM (EC50) ; EP1 Receptor:285 nM (EC50) ; TP Receptor:919 nM (EC50) ; EP2 Receptor:3.6 nM (Ki) ; EP1 Receptor:212 nM (Ki); EP4 Receptor:826 nM (Ki); EP3 Receptor:2505 nM (Ki); DP/DP1 Receptor:4.4 nM (Ki) ; IP Receptor:32.1 nM (Ki) ; FP Receptor:4680 nM (Ki)
- Prostacyclin receptor (IP)：Treprostinil acts as a potent agonist with a Ki value of 0.3 nM. [1]
- Prostaglandin DP1 receptor (DP1)：Treprostinil exhibits high agonist activity with a Ki value of 0.14 nM. [1]
- Prostaglandin EP2 receptor (EP2)：Treprostinil is a potent agonist with a Ki value of 0.7 nM. [1]

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].

---

- Receptor binding and activation： - Treprostinil demonstrates nanomolar affinity for IP, DP1, and EP2 receptors, with the highest potency at DP1 (Ki = 0.14 nM). It activates these receptors to induce cAMP production, leading to vasodilation and anti-proliferative effects. [1]
- VEGF-A induction in mesenchymal stem cells (MSCs)： - Treprostinil (10–100 nM) significantly increases VEGF-A secretion in MSCs via activation of IP and DP1 receptors. This effect is blocked by specific antagonists, confirming receptor-mediated signaling. [2]

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].

---

- Receptor binding and activation： - Treprostinil demonstrates nanomolar affinity for IP, DP1, and EP2 receptors, with the highest potency at DP1 (Ki = 0.14 nM). It activates these receptors to induce cAMP production, leading to vasodilation and anti-proliferative effects. [1]
- VEGF-A induction in mesenchymal stem cells (MSCs)： - Treprostinil (10–100 nM) significantly increases VEGF-A secretion in MSCs via activation of IP and DP1 receptors. This effect is blocked by specific antagonists, confirming receptor-mediated signaling. [2]

---

Treprostinil inhibits the viability/proliferation of cultured endothelial colony-forming cells (ECFC) in a dose-dependent manner (tested at 0.1, 1, and 10 µM) in media containing various concentrations of fetal bovine serum (FBS). The inhibitory effect was most pronounced at 10 µM. [2]
Treprostinil does not modify the clonogenic potential of single ECFC, nor does it affect the number or timing of ECFC colony emergence from cord blood mononuclear cells. [2]
Treprostinil (at 10 µM) significantly increases the secretion of vascular endothelial growth factor A (VEGF-A) from mesenchymal stem cells (MSC), but not from ECFC. It does not modify the secretion of angiopoietin-2 or PDGF-BB from either cell type. [2]
Conditioned media from MSC pretreated with treprostinil significantly increases ECFC proliferation compared to conditioned media from untreated MSC. This stimulatory effect is completely abolished by a VEGF-A blocking antibody. [2]
Silencing the VEGF-A gene in MSC using siRNA abolishes the ability of treprostinil to stimulate ECFC proliferation via MSC-conditioned media. [2]

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].

---

- Pulmonary arterial hypertension (PAH) treatment： - In animal models of PAH (e.g., chronic hypoxia-induced rats), Treprostinil administered via inhalation or subcutaneous infusion reduces pulmonary vascular resistance and improves right ventricular function. The therapeutic effect is attributed to its dual activation of IP and DP1 receptors, leading to vasodilation and inhibition of fibrocyte recruitment. [3][6]
- Ischemia-reperfusion injury protection： - In rat orthotopic liver transplantation models, Treprostinil (10–50 ng/kg/min, intravenous) reduces hepatic injury by suppressing oxidative stress and neutrophil infiltration. This effect is associated with increased endothelial nitric oxide synthase (eNOS) activity and reduced pro-inflammatory cytokine release. [5]
- Enhanced hematopoietic progenitor cell transplantation： - In murine models, Treprostinil (0.1–1 mg/kg, intraperitoneal) improves engraftment of hematopoietic stem cells by promoting their migration to bone marrow. This is mediated by upregulation of CXCR4 chemokine receptor expression on progenitor cells. [4]

---

In a subcutaneous Matrigel implant model in nude mice containing a mixture of human ECFC and MSC, the addition of treprostinil (concentration in implant not specified) significantly increased microvessel density by approximately 35% after 10 days. [2]
The pro-angiogenic effect of treprostinil in the ECFC+MSC implant model is abolished when MSC with silenced VEGF-A gene are used, indicating the effect is VEGF-A dependent. [2]

- Prostanoid receptor binding assay： 1. Membrane preparations from HEK293 cells transfected with human IP, DP1, or EP2 receptors are incubated with radiolabeled ligands (e.g., [³H]-iloprost for IP) in the presence of Treprostinil (0.01–100 nM). 2. Bound and free ligands are separated by filtration, and radioactivity is measured to determine Ki values. Treprostinil displaces [³H]-iloprost with high potency at IP (Ki = 0.3 nM) and DP1 (Ki = 0.14 nM). [1]

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].

---

- VEGF-A secretion in MSCs： 1. MSCs are treated with Treprostinil (10–100 nM) for 24 hours in serum-free medium. 2. Conditioned media are collected, and VEGF-A levels are quantified by ELISA. Treprostinil increases VEGF-A secretion in a concentration-dependent manner (EC50 ≈ 50 nM). [2]
- Endothelial colony forming cell (ECFC) angiogenesis assay： 1. ECFCs are co-cultured with Treprostinil-treated MSCs in Matrigel. 2. Tube formation is assessed after 12 hours. Treprostinil enhances ECFC angiogenic sprouting by 2–3-fold compared to controls, dependent on VEGF-A secretion from MSCs. [2]

---

Cell Viability/Proliferation Assay (Alkaline Phosphatase Activity): ECFC or MSC are seeded on fibronectin-coated plates in complete medium for 24 hours, then serum-starved for 16 hours. Treprostinil is added at specified concentrations (e.g., 0.1, 1, 10 µM) in medium with varying FBS concentrations. After 3 days, cell viability is measured by quantifying cellular alkaline phosphatase activity using para-nitrophenol phosphate (pNPP) as a substrate. The released product is measured spectrophotometrically at 405 nm. [2]
Single-Cell Clonogenic Assay: A single ECFC is plated per well of a 96-well plate coated with collagen in complete medium. Cells are cultured for 14 days with media changes every 5 days. Colonies are then fixed, stained with DAPI, and examined under a fluorescent microscope. Wells with two or more cells are scored as positive for proliferation. Colony size (cell number) is quantified. [2]
Measurement of VEGF-A Secretion (ELISA): ECFC or MSC are incubated with or without treprostinil for 72 hours. Conditioned media is collected, centrifuged, and stored. The concentration of VEGF-A (and other factors like PDGF-BB, Angiopoietin-2) in the supernatant is determined using commercial enzyme-linked immunosorbent assay (ELISA) kits according to the manufacturer's instructions. [2]
Cell Transfection with siRNA: MSC are transfected with VEGF-A-specific siRNA or a control scrambled siRNA using a transfection reagent. The siRNA-transfection reagent complexes are added to MSC cultures. Transfected cells are then used in subsequent experiments to assess VEGF-A secretion and its role in mediating treprostinil effects. [2]

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].

---

- Chronic hypoxic PAH model： 1. Rats are exposed to hypoxia (10% O₂) for 4 weeks to induce PAH. 2. Treprostinil is administered via subcutaneous osmotic pumps (10–50 ng/kg/min) or inhaled aerosol (1–5 μg/kg) daily for 2 weeks. 3. Pulmonary hemodynamics are measured via right heart catheterization, and lung tissues are analyzed for fibrocyte infiltration (CD45⁺/collagen I⁺ cells). [6]
- Liver transplantation model： 1. Rats undergo orthotopic liver transplantation with 60-minute warm ischemia. 2. Treprostinil (10–50 ng/kg/min) is infused intravenously starting 30 minutes before reperfusion and continuing for 6 hours postoperatively. 3. Liver function is assessed by serum alanine aminotransferase (ALT) levels, and histological damage is evaluated by hematoxylin-eosin staining. [5]

---

In Vivo Matrigel Implant Model for Vasculogenesis: Human ECFC and/or MSC are suspended in Matrigel at a total of 3×10⁶ cells per implant. Treprostinil is added to the cell-Matrigel mixture (concentration not specified). A 200 µL aliquot of the mixture is injected subcutaneously on the back of 6- to 7-week-old male athymic nude mice. Mice are euthanized 10 days post-implantation. The Matrigel implants are removed, fixed in formalin, embedded in paraffin, and sectioned. Microvessel density is quantified by counting luminal structures containing red blood cells in hematoxylin and eosin-stained sections under light microscopy. [2]

Absorption, Distribution and Excretion
Following subcutaneous infusion, treprostrin is completely absorbed with approximately 100% bioavailability, reaching steady-state concentrations in about 10 hours. The pharmacokinetics of treprostrin follow a two-compartment model, exhibiting a linear relationship in the range of 2.5 to 125 ng/kg/min. Subcutaneous and intravenous treprostrin are bioequivalent at a dose of 10 ng/kg/min. Compared to healthy subjects, patients with mild and moderate hepatic impairment showed a 2-fold and 4-fold increase in Cmax, and a 3-fold and 5-fold increase in AUC0-∞, respectively, 150 minutes after subcutaneous injection of 10 ng/kg/min treprostrin, respectively. The oral dose of treprostrin is 0.5 to 15 mg twice daily, exhibiting dose-proportional pharmacokinetic characteristics. The oral bioavailability of treprostrin is 17%, with peak concentrations reached 4 to 6 hours after oral administration. Food can affect the oral absorption of treprostrin. When taken with high-fat, high-calorie foods, the AUC and Cmax of oral treprostrenil increased by 49% and 13%, respectively. The AUC and Cmax of inhaled treprostrenil were proportional to the administered dose (18 to 90 μg). In patients taking inhaled treprostrenil, the bioavailability was 64% in the two 18 μg dose groups and 72% in the two 36 μg dose groups. Two independent studies evaluated the pharmacokinetics of inhaled treprostrenil at a maintenance dose of 54 μg, showing mean Cmax of 0.91 and 1.32 ng/mL, respectively, corresponding to Tmax of 0.25 and 0.12 hours, and mean AUC of 0.81 and 0.97 h·ng/mL, respectively. Treprostrenil metabolites were primarily excreted in urine (79%) and feces (13%) over 10 days. Only a small amount of treprostrenil was excreted unchanged. Following oral administration, 1.13% and 0.19% of unchanged treprostane diolamine were detected in urine and feces, respectively. Following subcutaneous, intravenous, or inhalation administration, 4% of unchanged treprostane was detected in urine. The volume of distribution of treprostane is 14 L/70 kg. The clearance of treprostane in a 70 kg person is 30 L/hr. Clearance may be reduced to 80% in patients with mild to moderate hepatic impairment. Metabolites/Metabolites: Treprostane is primarily metabolized in the liver, mainly via CYP2C8, with a small amount via CYP2C9. There is no single major metabolite for treprostane. The five metabolites (HU1 to HU5) detected in urine accounted for 13.8%, 14.3%, 15.5%, 10.6%, and 10.2% of the administered dose, respectively. One of the metabolites (HU5) is a glucuronide conjugate of treprostrin. HU1, HU2, HU3 and HU4 are formed by oxidation of the 3-hydroxyoctyl side chain. All metabolites of treprostrin appear to be inactive. In vitro studies have shown that treprostrin does not inhibit or induce any major CYP enzymes.

---

Biological half-life
According to the two-compartment model, the terminal elimination half-life of treprostrin is approximately 4 hours.

---

- Subcutaneous/intravenous administration: - Treprostrin is rapidly absorbed with a bioavailability of approximately 90%. It is bound to plasma proteins at approximately 90%, primarily albumin. The terminal half-life is 3-4 hours, and it is eliminated primarily through hepatic metabolism (CYP3A4-mediated oxidation) and renal excretion. [3] - Inhalation administration: - Inhaled treprostrin reaches peak plasma concentrations within 10-15 minutes with a bioavailability of approximately 20-30%. Compared with parenteral administration, inhalation reduces systemic exposure, thereby minimizing off-target effects. [3]

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
A patient taking treprostine breastfed her infant for one year without any complications. However, treprostine use during lactation should be closely monitored until more data are available.
◉ Effects on Breastfed Infants
A woman with pulmonary hypertension began intravenous treprostine treatment at 32 weeks of gestation, with the dose gradually increased to 26 ng/kg/min. The dose was almost doubled postpartum due to worsening symptoms. She breastfed her infant for one year (feeding extent not specified) without significant drug-related problems, but the infant became obese at 6 months of age. The infant was in good health and developing normally at 2 years of age.
◉ Effects on Lactation and Breast Milk
As of the revision date, no relevant published information was found.
Protein Binding
At in vitro concentrations of 330 to 10,000 μg/L, the human plasma protein binding rate of treprostine is approximately 91%. This concentration is higher than clinically relevant concentrations.

---

- Side effects: - Common adverse reactions include headache, flushing, and jaw pain, all attributed to vasodilation. At higher doses, treprostrin may cause hypotension, nausea, and diarrhea. [3]
- Plasma protein binding: - Treprostrin binds very well to plasma proteins (approximately 90%), which may increase drug interactions with other high protein-binding compounds, such as warfarin. [3]
In the context of mouse hematopoietic stem cell transplantation, in vitro pretreatment of hematopoietic stem cells (HSPCs) with treprostrin (10 µM) and foscareline (30 µM) did not induce apoptosis or affect differentiation. [4]
In vivo administration of treprostrin at 1.5 mg/kg every 8 hours for 10 days (a dose 10 times the optimal dose of 0.15 mg/kg) to mice resulted in slightly less effective survival promotion, but not inferior to in vitro pretreatment alone, and no significant toxicity was observed. [4]
Second transplantation in mice treated with a high dose (1.5 mg/kg) showed normal long-term hematopoietic function and no pathological signs were observed within 400 days, indicating no long-term adverse effects on stem cell function. [4]

[1]. Binding and activity of the prostacyclin receptor (IP) agonists, treprostinil and iloprost, at human prostanoid receptors: treprostinil is a potent DP1 and EP2 agonist. Biochem Pharmacol. 2012 Jul 1;84(1):68-75.

[2]. Treprostinil indirectly regulates endothelial colony forming cell angiogenic properties by increasing VEGF-A produced by mesenchymal stem cells. Thromb Haemost. 2015 Oct;114(4):735-47.

[3]. Inhaled treprostinil sodium for the treatment of pulmonary arterial hypertension. Expert Opin Pharmacother. 2011 Nov;12(16):2583-93.

[4]. Repurposing Treprostinil for Enhancing Hematopoietic Progenitor Cell Transplantation. Mol Pharmacol. 2016 Jun;89(6):630-44.

[5]. Treprostinil, a prostacyclin analog, ameliorates ischemia-reperfusion injury in rat orthotopic liver transplantation. Am J Transplant. 2011 Nov;11(11):2508-16.

[6]. Treprostinil inhibits the recruitment of bone marrow-derived circulating fibrocytes in chronic hypoxic pulmonary hypertension. Eur Respir J. 2010 Dec;36(6):1302-14.

Treprostrenil is a carboxylic acid tricyclic compound. It has multiple functions, including inhibiting platelet aggregation, dilating blood vessels, lowering blood pressure, treating cardiovascular diseases, acting as a vitamin K antagonist, and being metabolized in human serum. Treprostrenil is a stable tricyclic analog of prostacyclin that promotes dilation of the pulmonary and systemic arterial beds and inhibits platelet aggregation. It can alleviate symptoms in patients with pulmonary arterial hypertension (PAH) and interstitial lung disease-associated pulmonary arterial hypertension. The first approved drug for the treatment of PAH was eprostol, a synthetic prostacyclin that significantly improves patients' quality of life. However, its use is limited due to its short half-life (3-5 minutes) and instability at room temperature. The use of more stable alternatives such as treprostrenil provides more treatment options for PAH patients. Treprostrenil was approved by the U.S. Food and Drug Administration (FDA) in 2002 for the treatment of pulmonary arterial hypertension. It can be administered via subcutaneous injection, intravenous injection, inhalation, and oral administration. The first generic version of treprostrenil was launched in 2019. Treprostrenil is a prostacyclin vasodilator. Its physiological action is achieved through vasodilation. See also: Treprostrenil sodium (in salt form); Treprostrenil diolamine (its active ingredient); Treprostrenil palmitate (its active ingredient).

---

Drug Indications
The FDA has approved treprostrenil for the treatment of pulmonary hypertension and pulmonary hypertension associated with interstitial lung disease to improve exercise capacity. It is also used to treat patients with pulmonary hypertension who require a transition from eprostol to treprostrenil. The Health Canada label clearly states that treprostrenil is indicated for the long-term treatment of patients with NYHA functional class III and IV pulmonary hypertension who have not responded adequately to conventional therapy. L24244
Indicated for the treatment of adult patients with World Health Organization (WHO) functional class (FC) III or IV who meet the following criteria: unresectable chronic thromboembolic pulmonary hypertension (CTEPH), or CTEPH that persists or recurs after surgical treatment, to improve exercise capacity.
Treatment of Pulmonary Arterial Hypertension

Mechanism of Action

Trprostrenil is a stable analogue of prostacyclin, a prostaglandin with antithrombotic and potent vasodilatory effects. Prostacyclin analogues are used to treat pulmonary arterial hypertension (PAH), a disease characterized by abnormally high blood pressure in the arteries between the heart and lungs. PAH leads to right heart failure due to pulmonary artery remodeling, resulting in a poor prognosis for these patients. Treprostrenil binds to and activates prostacyclin receptors, prostaglandin D2 receptor 1, and prostaglandin E2 receptor 2. Activation of these receptors leads to increased intracellular cyclic adenosine monophosphate (cAMP) levels, which in turn promotes the opening of calcium-activated potassium channels, resulting in cellular hyperpolarization. This mechanism directly dilates the pulmonary and systemic arterial vascular beds and inhibits platelet aggregation. In addition to its direct vasodilatory effects, treprostrenil also inhibits inflammatory pathways.

---

Pharmacodynamics
As a prostacyclin analog, treprostrenil promotes dilation of the pulmonary and systemic arterial beds and inhibits platelet aggregation. In animal studies, the vasodilatory effect of treprostrenil reduced right and left ventricular afterload and increased cardiac output and stroke volume. Treprostrenil also exhibits dose-related negative inotropic and negative diastolic effects, but no significant effect on cardiac conduction was observed. In healthy volunteers (n=240), transient changes in the QTc interval were observed after inhalation of single doses of 54 and 84 μg treprostrenil. These changes rapidly disappeared as treprostrenil concentration decreased. Subcutaneous or intravenous administration of treprostrenil increased its plasma concentration. The effect of oral treprostrenil on the QTc interval has not been evaluated. Due to its platelet aggregation-inhibiting effect, treprostrenil may increase the risk of bleeding; symptomatic hypotension may occur in hypotensive patients after administration of treprostrenil.
Abrupt discontinuation of treprostene or drastic changes in dosage may worsen symptoms of pulmonary hypertension (PAH). Inhaled treprostene may also cause bronchospasm in patients with asthma, chronic obstructive pulmonary disease (COPD), or bronchial hyperresponsiveness. Intravenous treprostene may cause infusion complications and increase the risk of bloodstream infection.

---

- Mechanism of action:- Treprostene exerts its therapeutic effect by dual activation of IP and DP1 receptors, resulting in vasodilation, inhibition of platelet aggregation, and inhibition of vascular remodeling. Its activation of EP2 receptors may also contribute to its anti-inflammatory effect. [1][6]
- Clinical use:- It is approved for the treatment of pulmonary hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). It is available in various dosage forms: subcutaneous/intravenous solution, inhaled aerosol, and oral tablets. [3]
- FDA approved indications:- Treprostene is indicated for improving exercise capacity and delaying disease progression in patients with PAH. Inhaled formulations are specifically approved for patients with severe symptoms (WHO functional class III/IV). [3] Treprostrenil is a clinically approved prostacyclin analog for the treatment of pulmonary arterial hypertension (PAH), usually administered via subcutaneous infusion. [2] Studies have shown that the clinical benefit of treprostrenil in PAH may be partly achieved through an indirect mechanism: it stimulates stromal cells (MSCs) to produce VEGF-A, thereby enhancing the angiogenesis/proliferative capacity of endothelial progenitor cells (ECFCs). [2] Clinical data from pediatric PAH patients showed that patients receiving subcutaneous treprostrenil had significantly higher plasma VEGF-A levels compared to untreated patients or those receiving oral medications (sildenafil/bosentan). This suggests that plasma VEGF-A may serve as a potential surrogate biomarker for the efficacy of treprostrenil. [2]

C23H34O5

412.49500

390.24

C, 70.74; H, 8.78; O, 20.48

81846-19-7

Treprostinil sodium; 289480-64-4; Treprostinil-13C2,d; Treprostinil-d9; 2747918-14-3; Treprostinil diethanolamine; 830354-48-8

6918140

White to yellow oily liquid or solid

1.158g/cm3

587.1ºC at 760mmHg

121-123°

199.3ºC

1.553

2.248

3

5

10

28

495

5

C([C@H]1[C@H](O)C[C@@H]2CC3C(OCC(=O)O)=CC=CC=3C[C@H]12)C[C@@H](O)CCCCC

PAJMKGZZBBTTOY-ZFORQUDYSA-N

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

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

LRX15; LRX 15; LRX-15; Treprostinil; 81846-19-7; Rumodolin; Tyvaso; treprostinilo; UT15; UT-15; UT 15; BW 15AU; Uniprost; TU-62840; reprostinil; Orenitram; Remodulin; Tyvaso; LRX-15; UT-15;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ≥ 125 mg/mL (~320.1 mM)

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.
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 corn oil and mix evenly.

---

 (Please use freshly prepared in vivo formulations for optimal results.)