Table 8.1.
Pharmacological compounds that target UPR pathways with therapeutic implications
| Name | Target | Mechanism | Potential therapies | References |
|---|---|---|---|---|
| 4μ8c | IRE1α RNase | Inhibits XBP1 mRNA splicing. Inhibits RIDD function. | Atherosclerosis | Tufanli et al. (2017) |
| NAFLD | Lebeaupin et al. (2018a, b) | |||
| STF-083010 | Diabetes | Lerner et al. (2012) | ||
| Inflammatory diseases | Kim et al. (2015) | |||
| Atherosclerosis | Tufanli et al. (2017) | |||
| NAFLD | Lebeaupin et al. (2018a, b) | |||
| MKC-3946 | Multiple Myeloma | Mimura et al. (2012) | ||
| KIRA6/ KIRA8 | IRE1α kinase and RNase | Promotes cell survival under ER stress. | Diabetes | Ghosh et al. (2014) |
| Diabetes | Morita et al. (2017) | |||
| APY29 | IRE1α kinase | ATP-competitive inhibitor that inhibits IRE1α kinase, but increases dimerization/oligomerization of IRE1α, enhancing RNase activity. | ND | Korennykh et al. (2009) |
| ND | Wang et al. (2012) | |||
| Kidney cancer | Kuo et al. (2017) | |||
| Selonsertib | ASK1 | Inhibits ASK1-JNK1 signaling with potential anti-inflammatory, and anti-fibrotic activities. | NAFLD with fibrosis | Loomba et al. (2017) |
| Multidrug resistance | Ji et al. (2019) | |||
| GSK2606414 GSK2656157 | PERK | Inhibits PERK autophosphorylation. | Cancer (tumor development and angiogenesis) | Axten et al. (2013) Atkins et al. (2013) |
| Parkinson’s disease | Mercado et al. (2018) | |||
| Salubrinal | P-eIF2α | Prevents eIF2α dephosphorylation, maintaining mRNA translation inhibition to limit the ER protein load. | Liver cancer | Vandewynckel et al. (2015) |
| Guanabenz | ND | Tsaytler et al. (2011) | ||
| Sephin1 | Charcot-Marie-Tooth disease and amyotrophic lateral sclerosis | Das et al. (2015) | ||
| ND | Crespillo-Casado et al. (2017) | |||
| Multiple sclerosis | Chen et al. (2019) | |||
| Raphin1 | Huntington’s disease | Krzyzosiak et al. (2018) | ||
| ISRIB 2BAct | P-eIF2α | Inhibits P-eIF2α to resume global mRNA translation. | ND | Sidrauski et al. (2015) |
| ND | Tsai et al. (2018) | |||
| ND | Zyryanova et al. (2018) | |||
| Vanishing white matter disease | Wong et al. (2019) | |||
| ML291 | CHOP | Selective CHOP inducer with anti-proliferative effects. | ND | Flaherty et al. (2013) and Flaherty et al. (2014) |
| PACMA 31 | PDI | PDI inhibitors increases ER stress to reduce cell viability with anti- proliferative effects. | Ovarian cancer | Badolato et al. (2017) |
| Bacitracin | Glioblastoma | Goplen et al. (2006) | ||
| AEBSF | ATF6 | Prevents ATF6 proteolytic cleavage in the Golgi and activation. | ND | Okada et al. (2003) |
| Ceapins | ATF6 | Traps ATF6 in the ER to prevent activation. | ND | Gallagher et al. (2016) |
| 147 | ATF6 | Localized metabolic activation of ATF6 to enhance proteostasis. | ND | Plate et al. (2016) |
| ND | Paxman et al.(2018) | |||
| Cardiac ischemia/reperfusion damage | Blackwood et al.(2019) |
ND: therapeutic function in vivo not determined