The invention provides compounds for activating the activating transcription factor 6 (ATF6) arm of the unfolded protein response (UPR), or activating the transcriptional targets of ATF6, in the endoplasmic reticulum of a cell, the compounds being of any of formulas (I) through (IX) as described herein. The compounds can be used for treatment of conditions involving gain-of-toxic-function and loss-of-function folding disorders including lysosomal storage diseases, antitrypsin-associated emphysema and similar diseases. These molecules are also expected to have disease-ameliorating effects in Alzheimer's disease and diabetes.
本发明提供了用于激活细胞内质网中未折叠蛋白反应(
UPR)的激活转录因子6(
ATF6)臂或激活
ATF6的转录靶标的化合物,所述化合物为本文所述的式(I)至式(IX)中的任何一种。这些化合物可用于治疗涉及毒性功能增益和功能丧失折叠障碍的疾病,包括溶酶体贮积疾病、抗胰
蛋白酶相关性肺气肿和类似疾病。这些分子还有望对阿尔茨海默病和糖尿病产生疾病改善作用。