289480-64-4
基本信息
曲前列素
曲前列尼爾鈉
曲前列尼爾酸
曲前列環(huán)素鈉鹽
曲前列尼爾鈉9(瑞莫杜林)
曲前列尼爾鈉9(瑞莫杜林) 1G
曲前列尼爾鈉289480-64-4,工廠零售289480-64-4
Treprostinil Sodium API
Treprostinil sodium salt
Treprostinil Sodium (UT-15)
289480-64-4 Treprostinil Sodium
物理化學性質
常見問題列表
吸入曲前列素鈉(一種前列環(huán)素類似物)是最近獲得FDA批準用于治療致命性孤兒疾病的藥物:肺動脈高壓(PAH)。與安慰劑相比,曲前列環(huán)素可保留竇狀內皮細胞襯里并減少移植后早期的血小板沉積。安慰劑組的肝組織血流明顯受損,而曲前列環(huán)素維持血流量與正常水平相似。前列腺素治療顯著增加內皮細胞集落形成細胞與間充質干細胞在裸鼠移植的基質膠中的血管形成能力。在間充質干細胞中沉默VEGF-A基因也會阻斷曲前列環(huán)素的促血管生成作用。曲前列環(huán)素在提高小鼠和人類造血干細胞和祖細胞中的細胞內cAMP水平方面最有效。與常氧小鼠相比,用曲前列環(huán)素治療顯著減少細胞募集。曲前列環(huán)素還可降低右心室收縮壓并略微減少血管重塑,但無法逆轉右心室肥厚。
Target | Value |
EP2
(Cell-free assay) | 3.6 nM(Ki) |
DP1
(Cell-free assay) | 4.4 nM(Ki) |
IP
(Cell-free assay) | 32 nM(Ki) |
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.
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.