Treprostinil

Details:

• CAS number :81846-19-7

  English name :REMODULIN

  Chinese name: Qu Prostenil

  CBNumber:CB7231250

  Molecular formula :C23H34O5

  Molecular weight :390.51

  MOL File:81846-19-7.mol
  Chemical properties of troprostil

  Melting point :121-123°

  Boiling point :587.1±50.0 °C(Predicted)

  Density :1.158± 0.06g /cm3(Predicted)

  Storage conditions :Sealed in dry,Store in freezer, under -20°C

  Solubility :Chloroform (Slightly, Heated), Methanol (Slightly, Heated)

  Form :Solid

  Acidity coefficient (pKa) :3.19±0.10(Predicted)

  Color :Off-White to Beige
  Properties, uses and production technology of troprostil
  Troprostil is a chemical formula and a drug. Traprostil acts primarily by directly dilating the lung and systemic arterial bed and inhibiting platelet aggregation.

  Overview In 2002, subcutaneous injection of traprostacycline was approved in the United States for the treatment of pulmonary hypertension, in 2006 it was approved in the European Union, and in 2004 intravenous infusion of traprostacycline for the treatment of pulmonary hypertension was also approved in the United States.

  Bioactive Treprostinil (LRX-15) is a highly potent DP1 and EP2 agonist with EC50 values of 0.6±0.1 and 6.2±1.2 nM, respectively.

  Target point

  DP/DP1 Receptor   0.6 nM (EC 50 )

  IP Receptor   1.9 nM (EC 50 )

  EP 2 Receptor   6.2 nM (EC 50 )

  EP3 Receptor   68.9 nM (EC 50 )

  EP 4 Receptor   181 nM (EC 50 )

  EP 1 Receptor   285 nM (EC 50 )

  TP Receptor   919 nM (EC 50 )

  EP 2 Receptor   3.6 nM (Ki)

  EP 1 Receptor   212 nM (Ki)

  EP 4 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)

• In vitro study

• Treprostinil has high affinity for the DP1, EP2 and IP receptors (K _i =4.4, 3.6 and 32 nM, respectively), low affinity for EP1 and EP4 receptors 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 arteries.Treprostinil inhibits viability of cultured endothelial colony forming cells. Endothelial colony forming cells proliferation is stimulated by conditioned media from Treprostinil pretreated mesenchymal stem cells.

   

   

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• 体内研究

  Inhaled treprostinil sodium, a prostacyclin analog, is the most recent agent to receive FDA approval for the treatment of a fatal orphan disease: pulmonary arterial hypertension (PAH). Treprostinil preserves the sinusoidal endothelial cell lining and reduces platelet deposition early post-transplantation compared to placebo. Hepatic tissue blood flow is significantly compromised in the placebo group, whereas treprostinil maintains blood flow similar to normal levels.Treprostinil treatment significantly increases the vessel-forming ability of endothelial colony forming cells combined with mesenchymal stem cells in Matrigel implanted in nude mice. Silencing VEGF-A gene in mesenchymal stem cells also blocks the pro-angiogenic effect of Treprostinil. Treprostinil is most efficacious in raising intracellular cAMP levels in murine and human hematopoietic stem and progenitor cells. Treatment with Treprostinil significantly reduces the recruitment of cells compared to normoxic mice. Treprostinil also reduces right ventricular systolic pressure and slightly reduces the vascular remodelling but fails to reverse the right ventricular hypertrophy.