Abstract: Provided herein are compounds that activate IRE1/XBP1s, and pharmaceutically acceptable derivatives thereof. Also provided are pharmaceutical compositions containing the compounds and methods of using the compounds for treating a subject having a disease or disorder that may be ameliorated by increasing IRE1/XBP1s activity.

Abstract: Disclosed herein are compounds, their pharmaceutical salts, and pharmaceutical compositions that selectively activate the inositol-requiring enzyme 1 (IRE1)/X-box binding protein 1 (XBP1s) signaling pathway of the unfolded protein response (UPR), but that do not target the IRE1 kinase domain. The compounds are useful in treating diseases or conditions characterized by imbalances in proteostasis within the endoplasmic reticulum (ER) or secretory pathway, including those not associated with ER stress or activation of UPR.

Abstract: 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.

Abstract: 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.

Abstract: Disclosed herein are compounds, their pharmaceutical salts, and pharmaceutical compositions that selectively activate the inositol-requiring enzyme 1 (IRE1)/X-box binding protein 1 (XBP1s) signaling pathway of the unfolded protein response (UPR), but that do not target the IRE1 kinase domain.

Abstract: 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.