公开(公告)号：US20120220546A1

公开(公告)日：2012-08-30

申请号：US13462991

申请日：2012-05-03

申请人： Matías Antonio Avila Zaragoza ,  Jesús Maria Bañales Asurmendi ,  Maria Carmen Berasain Lasarte ,  Fernando José Corrales Izquierdo ,  MarÍa del Carmen Gil Puig ,  María Ujue Latasa Sada ,  Jon Lecanda Cordero ,  Jesús Maria Prieto Valtueña ,  Carlos Manuel Rodríguez Ortigosa

发明人： Matías Antonio Avila Zaragoza ,  Jesús Maria Bañales Asurmendi ,  Maria Carmen Berasain Lasarte ,  Fernando José Corrales Izquierdo ,  MarÍa del Carmen Gil Puig ,  María Ujue Latasa Sada ,  Jon Lecanda Cordero ,  Jesús Maria Prieto Valtueña ,  Carlos Manuel Rodríguez Ortigosa

IPC分类号： A61K31/7076 ,  A61P1/16 ,  A61P35/00 ,  C07H19/167

CPC分类号： A61K31/7076 ,  A61K31/00 ,  A61K45/06 ,  A61K2300/00

摘要： 5′-methylthioadenosine (MTA) is described as a compound that is susceptible to inhibiting and/or blocking the epithelial-mesenchymal transition (EMT), a process whereby epithelial cells become mesenchymal cells.The periodical intake of MTA [every 24 h for 21 days] significantly improves fibrosis and the markers for hepatic cellular damage in KO-Mdr2 mice with MTA (28 mg/kg). Following the daily oral administration of MTA, both the expression of EMT markers in the total liver and appreciable signs of fibrosis are significantly reduced, indicating the beneficial effect of MTA on the liver affected by the lack of Mdr2. MTA is proposed to be a safe drug, suitable for oral formulation and without secondary effects, to be used in the prevention and/or treatment of diseases associated with EMT, including chronic cholestatic diseases, fibrosis and cholangiocarcinoma. On the other hand, MTA is proposed for application in anti-tumor therapies by inhibiting or blocking the EMT properties of CSC cells, in order to improve the prognosis of tumor development and the malignancy thereof.

摘要翻译： 5'-甲基硫代腺苷（MTA）被描述为易于抑制和/或阻断上皮 - 间质转化（EMT）的化合物，其是上皮细胞成为间充质细胞的过程。 MTA（28天/ 21天）的定期摄入显着改善了MTA（28mg / kg）的KO-Mdr2小鼠的纤维化和肝细胞损伤的标志物。 在每日口服MTA后，EMT标志物在总肝中的表达和纤维化的明显迹象均显着降低，表明MTA对缺乏Mdr2的肝脏有益效果。 MTA被认为是一种安全的药物，适用于口服制剂和无次要作用，用于预防和/或治疗与EMT有关的疾病，包括慢性胆汁淤积性疾病，纤维化和胆管癌。 另一方面，通过抑制或阻断CSC细胞的EMT特性，提出MTA用于抗肿瘤治疗，以改善肿瘤发展的预后及其恶性。