| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
| Targets |
IP Receptor ( EC50 = 1.9 nM ); TP Receptor ( EC50 = 919 nM ); IP Receptor ( Ki = 32.1 nM ); IP Receptor ( Ki = 4680 nM )
Treprostinil diethanolamine targets prostacyclin (IP), prostaglandin D2 (DP1), and prostaglandin E2 (EP2) receptors. It is a potent agonist with Ki values of 3.6 nM (EP2), 4.4 nM (DP1), 32.1 nM (IP), 212 nM (EP1), 826 nM (EP4), 2505 nM (EP3), and 4680 nM (FP). By activating these receptors, particularly IP, the compound induces vasodilation and inhibits platelet aggregation. These effects are mediated through increased intracellular cAMP levels. |
|---|---|
| ln Vitro |
With EC50 values of 0.6 nM, 6.2 nM, and 1.9 nM, respectively, 36-vs, trezostinil diethanolamine (UT-15C; 0.001-10,000 nM; 60 minutes; HEK293 cells) potently activates IP receptors, DP1 and EP2 receptors, and IP receptors. The activity of the EP3 receptor is 95 times lower, the activity of the EP4 receptor is 95 times lower, and the activity of the EP1 site is 150 times lower than that of IP receptors [1]. Human and mouse hematopoietic stem and progenitor cells (HSPCs) accumulate more cAMP when treated with treprostinil diethanolamine (10 μM) [2]. The effects of SDF-1 are enhanced by treprostinil diethanolamine (10 μM; 2–6 hours; PC3 cells) through CXCR4 [2].
In vitro, Treprostinil diethanolamine acts as a potent agonist at prostacyclin (IP), DP1, and EP2 receptors with Ki values of 32.1, 4.4, and 3.6 nM, respectively. It induces vasodilation of human pulmonary arteries. The compound increases intracellular cAMP levels through Gs protein-coupled receptor activation. These in vitro activities demonstrate its potential for treating pulmonary arterial hypertension and other vascular disorders. |
| ln Vivo |
The administration of treprostinil diethanolamine (UT-15C; 0.15 mg/kg; i.h.; every 8 hours; for 10 days; BALB/c mice) improves bone marrow reconstitution and HSPC repopulation [2]. In lethally irradiated recipient mice, treprostinil diethanolamine (0.15 mg/kg) administered intravenously every 8 hours for 10 days increases survival [2]. Male Lewis rats treated with treprostinil diethanolamine (0.1 mg/kg; ih; 24 h) had increased expression of IL-10 and decreased mRNA expression of TNF-α and IFN-γ [3].
In vivo, Treprostinil diethanolamine is used for the treatment of pulmonary arterial hypertension (PAH). It is administered via various routes including intravenous, subcutaneous, and inhalation. The compound causes vasodilation of pulmonary arteries, reducing pulmonary vascular resistance and improving hemodynamics. It also inhibits platelet aggregation. Clinical studies have demonstrated its efficacy in improving exercise capacity and hemodynamic parameters in PAH patients. |
| Enzyme Assay |
In vitro receptor binding assays are used to characterize Treprostinil diethanolamine's affinity for prostacyclin and prostaglandin receptors. Membrane preparations from cells expressing the target receptors are incubated with radiolabeled ligands and varying concentrations of the compound. Bound radioactivity is measured, and Ki values are calculated from competition curves. Functional assays measure cAMP accumulation in cells expressing the receptors.
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| Cell Assay |
Cell-based assays for Treprostinil diethanolamine are conducted in cells expressing prostacyclin and prostaglandin receptors. Cells are treated with the compound at various concentrations, and cAMP levels are measured by ELISA or HTRF-based assays. Vasodilation is assessed in isolated pulmonary artery preparations. These assays characterize the compound's potency and efficacy at the target receptors.
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| Animal Protocol |
Animal/Disease Models: balb/c (Bagg ALBino) mouse [2]
Doses: 0.15 mg/kg Route of Administration: subcutaneous injection; every 8 hrs (hrs (hours)); for 10 days Experimental Results: Increased survival rate of recipient mice exposed to lethal radiation. Animal/Disease Models: Male Lewis rat [3] Doses: 0.1 mg/kg Route of Administration: subcutaneous injection; 24-hour Experimental Results: The mRNA expression of TNF-α and IFN-γ diminished, and the expression of IL-10 increased. In vivo animal experiments with Treprostinil diethanolamine are conducted in models of pulmonary hypertension. The compound is administered via various routes, and hemodynamic parameters including pulmonary artery pressure and vascular resistance are measured. Efficacy is assessed by improvement in exercise capacity and survival. Specific protocols vary depending on the animal model and research objectives. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Treprostinil diethanolamine include good bioavailability via various routes of administration. The compound has a relatively short half-life requiring continuous or frequent administration. It is metabolized primarily by the liver. Specific PK parameters depend on the route of administration. Solubility: DMF 20 mg/mL, DMSO 5 mg/mL, Ethanol 13 mg/mL, PBS (pH 7.2) 5 mg/mL. Storage: appropriately.
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| Toxicity/Toxicokinetics |
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 nearly doubled postpartum due to worsening symptoms. She breastfed her infant for one year (feeding extent unspecified) 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 No relevant published information was found as of the revision date. Safety and toxicology data for Treprostinil diethanolamine have been evaluated in preclinical and clinical studies. Common adverse effects include headache, nausea, diarrhea, and injection site reactions. The compound is approved for clinical use in pulmonary arterial hypertension. However, for research purposes, appropriate safety precautions should be followed. |
| References |
[1]. Whittle BJ, et, al. 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]. Kazemi Z, et, al. Repurposing Treprostinil for Enhancing Hematopoietic Progenitor Cell Transplantation. Mol Pharmacol. 2016 Jun;89(6):630-44. [3]. Ghonem N, et, al. Treprostinil, a prostacyclin analog, ameliorates ischemia-reperfusion injury in rat orthotopic liver transplantation. Am J Transplant. 2011 Nov;11(11):2508-16. |
| Additional Infomation |
See also: Treprostil (containing active ingredient).
Drug Indications Treatment of pulmonary hypertension Treprostinil diethanolamine has CAS number 830354-48-8, molecular formula C27H45NO7, and molecular weight 495.65. Synonyms: Treprostinil diolamine, UT-15C. It is a potent EP2, DP1, and IP agonist with Ki values of 3.6, 4.4, and 32.1 nM, respectively. It is used for the treatment of pulmonary arterial hypertension. Purity: >98%. Not for over-the-counter use; for research and clinical applications. |
| Molecular Formula |
C27H45NO7
|
|---|---|
| Molecular Weight |
495.65
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| Exact Mass |
495.32
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| Elemental Analysis |
C, 65.43; H, 9.15; N, 2.83; O, 22.59
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| CAS # |
830354-48-8
|
| Related CAS # |
Treprostinil;81846-19-7;Treprostinil sodium;289480-64-4
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| PubChem CID |
11179459
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| Appearance |
Solid powder
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| Hydrogen Bond Donor Count |
6
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
14
|
| Heavy Atom Count |
35
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| Complexity |
524
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| Defined Atom Stereocenter Count |
5
|
| SMILES |
CCCCC[C@@H](CC[C@@H]1[C@H]2CC3=C(C[C@H]2C[C@H]1O)C(=CC=C3)OCC(=O)O)O.C(CO)NCCO
|
| InChi Key |
RHWRWEUCEXUUAV-ZSESPEEFSA-N
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| InChi Code |
InChI=1S/C23H34O5.C4H11NO2/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)256-3-1-5-2-4-7/h5-6,8,16-19,21,24-25H,2-4,7,9-14H2,1H3,(H,26,27)5-7H,1-4H2/t16-,17-,18+,19-,21+/m0./s1
|
| Chemical Name |
2-((1R,2R,3aS,9aS)-2-Hydroxy-1-(3(S)-hydroxyoctyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta(b)naphthalen-5-yloxy)acetic acid diethanolamine salt
|
| Synonyms |
UT15C; UT-15C;Treprostinil diolamine; 830354-48-8; Treprostinil diethanolamine; UT-15C; treprostinil diolamin; Orenitram; UNII-H1FKG90039; Treprostinil diolamine [USAN]; UT 15C
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0176 mL | 10.0878 mL | 20.1755 mL | |
| 5 mM | 0.4035 mL | 2.0176 mL | 4.0351 mL | |
| 10 mM | 0.2018 mL | 1.0088 mL | 2.0176 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.
Phase III Clinical Worsening Study of UT-15C i
A 12-Week, International, Multicenter, Double-Blind, Randomized, Placebo-Controlled Comparison of the Efficacy and Safety of Oral UT-15C Sustained Release Tablets in Subjects with Pulmonary Arterial Hypertension
CTID: null
Phase: Phase 3 Status: Completed
Date: 2007-02-19
Products are for research use only; We do not sell to patients
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