公开(公告)号：WO2016196895A1

公开(公告)日：2016-12-08

申请号：PCT/US2016/035669

申请日：2016-06-03

申请人： JOSLIN DIABETES CENTER, INC.

发明人： TSENG, Yu-hua ,  LYNES, Matthew ,  XUE, Ruidan

IPC分类号： A61K31/7105 ,  A61K31/713 ,  A61K48/00

CPC分类号： A61K35/35 ,  A61K35/545 ,  A61K38/1719 ,  A61K38/177 ,  A61K38/1796 ,  A61K38/465 ,  C07K14/705 ,  C12N5/0653 ,  C12Y301/03048

摘要： The invention provides methods and compositions relating to molecular targets identified as being capable of increasing or decreasing thermogenic potential in cells, including preadipocytes. Included in the invention are methods and compositions relating to inhibiting or suppressing the activity of an uncoupling protein 1 (UCPl) negative regulator, such as cardiac actin 1 (ACTCl), somatostatin receptor 1 (SSTRl), FAT atypical cadherin 1 (FAT1), and protein tyrosine phosphatase receptor type B (PTPRB). Also included in the invention are methods and compositions relating to activating a UCPl positive regulator, such as phosphatidylinositol-3,4,5,-triphosphate-dependent Rac exchange factor 1 (PREXl), cortactin binding protein 2 (CTTNBP2), doublesex and mab-3-related transcription factor- like family Al (DMRTA1), and endothelin receptor type B (ENDRB). The invention also provides methods and compositions relating to enrichment of cells having thermogenic potential based on cell surface markers, e.g., CD29, identified as being predictive of such.

摘要翻译： 本发明提供了与被鉴定为能够增加或降低细胞（包括前脂肪细胞）的生热潜能的分子靶标相关的方法和组合物。 本发明包括与抑制或抑制解偶​​联蛋白1（UCP1）阴性调节剂如心肌肌动蛋白1（ACTC1），生长抑素受体1（SSTR1），FAT非典型钙粘着蛋白1（FAT1）的活性相关的方法和组合物， 和B型蛋白酪氨酸磷酸酶受体（PTPRB）。 本发明还包括与激活UCP1阳性调节剂有关的方法和组合物，例如磷脂酰肌醇-3,4,5，三磷酸依赖性Rac交换因子1（PREX1），皮质激素结合蛋白2（CTTNBP2），双联体和mab -3相关转录因子样家族Al（DMRTA1）和B型内皮素受体（ENDRB）。 本发明还提供了关于基于细胞表面标志物（例如CD29）识别为具有预测性的具有产生发热潜力的细胞的富集的方法和组合物。