1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETreprostinil sodiumCat. No.: HY-16504CAS No.: 289480-64-4Synonyms: UT-15分式: CHNaO分量: 412.49作靶點(diǎn): Prostaglandin Receptor作通路: GPCR/G Protein儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 26 m

2、g/mL (63.03 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.4243 mL 12.1215 mL 24.2430 mL5 mM 0.4849 mL 2.4243 mL 4.8486 mL10 mM 0.2424 mL 1.2122 mL 2.4243 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Treprostinil sodium效的DP1和EP

3、2激動(dòng)劑，其EC50值分別為0.60.1和6.21.2 nM。IC50 & Target DP/DP1 Receptor IP Receptor EP2 Receptor EP3 Receptor0.6 nM (EC50) 1.9 nM (EC50) 6.2 nM (EC50) 68.9 nM (EC50)1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEEP4 Receptor EP1 Receptor TP Receptor EP2 Receptor181 nM (EC50) 285 nM (EC50) 919 nM (EC50) 3.6 n

4、M (Ki)EP1 Receptor EP4 Receptor EP3 Receptor DP/DP1 Receptor212 nM (Ki) 826 nM (Ki) 2505 nM (Ki) 4.4 nM (Ki)IP Receptor FP Receptor32.1 nM (Ki) 4680 nM (Ki)體外研究 Treprostinil has high affinity for the DP1, EP2 and IP receptors (Ki=4.4, 3.6 and 32 nM, respectively), lowaffinity for EP1 and EP4 recepto

5、rs and even lower affinity for EP3, FP and TP receptors. Activation of IP,DP1 and EP2 receptors, as with treprostinil, can all result in vasodilatation of human pulmonary arteries1.Treprostinil inhibits viability of cultured endothelial colony forming cells. Endothelial colony forming cellsprolifera

6、tion is stimulated by conditioned media from Treprostinil pretreated mesenchymal stem cells 5.體內(nèi)研究 Inhaled treprostinil sodium, a prostacyclin analog, is the most recent agent to receive FDA approval for thetreatment of a fatal orphan disease: pulmonary arterial hypertension (PAH) 2. Treprostinil pr

7、eserves thesinusoidal endothelial cell lining and reduces platelet deposition early post-transplantation compared toplacebo. Hepatic tissue blood flow is significantly compromised in the placebo group, whereas treprostinilmaintains blood flow similar to normal levels 3.Treprostinil treatment signifi

8、cantly increases the vessel-forming ability of endothelial colony forming cells combined with mesenchymal stem cells in Matrigelimplanted in nude mice. Silencing VEGF-A gene in mesenchymal stem cells also blocks the pro-angiogeniceffect of Treprostinil 4. Treprostinil is most efficacious in raising

9、intracellular cAMP levels in murine andhuman hematopoietic stem and progenitor cells 5. Treatment with Treprostinil significantly reduces therecruitment of cells compared to normoxic mice. Treprostinil also reduces right ventricular systolic pressureand slightly reduces the vascular remodelling but

10、fails to reverse the right ventricular hypertrophy 6.PROTOCOLCell Assay 5 Human or murine hematopoietic stem and progenitor cells are incubated in the presence of vehicle or thecombination of 10 M Treprostinil and 30 M forskolin at 37C for 1 hour and 24 hours. After washing withphosphate-buffered sa

11、line at 4C, cells are stained for externalized phosphatidylserine with the apoptosis kit5.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats 3Administration 36 Male Lewis rats weighing 200-300 g are used in the study. Donor animals receive trep

12、rostinil or placebo 24 hbefore hepatectomy and the corresponding recipient animal receive the similar treatment until the time ofsacrifice. The surgeon is blinded to treatment. Recipients are sacrificed at 1, 3, 6, 24 and 48 h post-transplantation to examine the early events after IRI. Treprostinil

13、(100 ng/kg/min) or placebo is administeredsubcutaneously via an Alzet implantable osmotic pump. This dose is selected to achieve a steady-stateplasma concentration in the range of 5-20 ng/mL 3.Mice 62/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBone marrow transplanted (BMT) mice are divided into

14、 five different groups with each group consisting of 6to 10 mice. One group of mice is exposed to hypoxia (10% inspired oxygen fraction) in a normobaricchamber whereas the second group (control BMT) of animals are placed in a normoxic chamber with anormal oxygen environment (21% inspired O2 fraction

15、) for 28 days. Sham group mice receive salinetreatment whereas two other groups of mice receive Treprostinil infusions of different dose levels (14 ng/kgand 70 ng/kg per minitue) and are exposed to hypoxia for 4 weeks. For comparison, human infusion rates inPAH therapy vary from 10 to 60 ng/kg per m

16、in 6.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. 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.

17、Biochem Pharmacol. 2012 Jul 1;84(1):68-75.2. Ferrantino M, et al. Inhaled treprostinil sodium for the treatment of pulmonary arterial hypertension. Expert Opin Pharmacother. 2011Nov;12(16):2583-93.3. Ghonem N, et al. Treprostinil, a prostacyclin analog, ameliorates ischemia-reperfusion injury in rat

18、 orthotopic liver transplantation. Am JTransplant. 2011 Nov;11(11):2508-16.4. Smadja DM, et al. Treprostinil indirectly regulates endothelial colony forming cell angiogenic properties by increasing VEGF-A producedby mesenchymal stem cells. Thromb Haemost. 2015 Oct;114(4):735-47.5. Kazemi Z, et al. Repurposing Treprostinil for Enhancing Hematopoietic Progenitor Cell Transplantation. Mol Pharmacol. 2016Jun;89(6):630-44.6. Nikam VS, et al. Treprostinil inhibits the recruitment of bone marrow-derived circulating fibrocy