unfolded protein response (upr)

ErSO 是一种通过 ERα 受体的，预期未折叠蛋白反应 (UPR) 的特异性激活剂。 ErSO 可用于抗癌研究。

Ceapin-A7 是内质网应激 ATF6α信号的选择性阻断剂(IC50:0.59 μM)，可用于探讨 ATF6α 促细胞活化的机制及其在病理环境中的作用。

AA147 (ATF6-activator-147) 是小分子内质网蛋白稳态调节剂，能够选择性激活未折叠蛋白反应的 ATF6臂。

BHPI is a potent inhibitor of nuclear estrogen–ERα-regulated gene expression. Elicits sustained ERα-dependent activation of the endoplasmic reticulum (EnR) stress sensor, the unfolded protein response (UPR), and persistent inhibition of protein synthesis.

ML291 is a sufonamidebenzamide compound that induces the unfolded protein response (UPR) and overwhelms the adaptive capacity of UPR, resulting in apoptosis in various solid cancer models. It activates the PERK eIF2a CHOP apoptotic pathway of UPR and reduces leukemic cell burden [1].

UPR-IN-17# is an effective pan-inhibitor of the unfolded protein response.

Nemorosone is a polycyclic polyprenylated acylphloroglucinol (PPAP) originally isolated from C. rosea that has antiproliferative properties.1 Nemorosone inhibits growth of NB69, Kelly, SK-N-AS, and LAN-1 neuroblastoma cells (IC50s = 3.1-6.3 μM), including several drug-resistant clones, but not MRC-5 human embryonic fibroblasts (IC50 = >40 μM).2 It increases DNA fragmentation in LAN-1 cells in a dose-dependent manner, and decreases N-Myc protein levels and phosphorylation of ERK1 2 by MEK1 2. Nemorosone also inhibits growth of Capan-1, AsPC-1, and MIA-PaCa-2 pancreatic cancer cells (IC50s = 4.5-5.0 μM following a 72-hour treatment) but not human dermal and foreskin fibroblasts (IC50s = >35 μM).1 It induces apoptosis, abolishes the mitochondrial membrane potential, and increases cytosolic calcium concentration in pancreatic cancer cells in a dose-dependent manner. Nemorosone activates the caspase cascade in a dose-dependent manner and inhibits cell cycle progression, increasing the proportion of cells in the G0 G1 phase, in both neuroblastoma and pancreatic cancer cells.1,2 Nemorosone (50 mg kg, i.p., per day) also reduces tumor growth in an MIA-PaCa-2 mouse xenograft model.3References1. Holtrup, F., Bauer, A., Fellenberg, K., et al. Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR). Br. J. Pharmacol. 162(5), 1045-1059 (2011).2. Díaz-Carballo, D., Malak, S., Bardenheuer, W., et al. Cytotoxic activity of nemorosone in neuroblastoma cells. J. Cell. Mol. Med. 12(6B), 2598-2608 (2008).3. Wold, R.J., Hilger, R.A., Hoheisel, J.D., et al. In vivo activity and pharmacokinetics of nemorosone on pancreatic cancer xenografts. PLoS One 8(9), e74555 (2013). Nemorosone is a polycyclic polyprenylated acylphloroglucinol (PPAP) originally isolated from C. rosea that has antiproliferative properties.1 Nemorosone inhibits growth of NB69, Kelly, SK-N-AS, and LAN-1 neuroblastoma cells (IC50s = 3.1-6.3 μM), including several drug-resistant clones, but not MRC-5 human embryonic fibroblasts (IC50 = >40 μM).2 It increases DNA fragmentation in LAN-1 cells in a dose-dependent manner, and decreases N-Myc protein levels and phosphorylation of ERK1 2 by MEK1 2. Nemorosone also inhibits growth of Capan-1, AsPC-1, and MIA-PaCa-2 pancreatic cancer cells (IC50s = 4.5-5.0 μM following a 72-hour treatment) but not human dermal and foreskin fibroblasts (IC50s = >35 μM).1 It induces apoptosis, abolishes the mitochondrial membrane potential, and increases cytosolic calcium concentration in pancreatic cancer cells in a dose-dependent manner. Nemorosone activates the caspase cascade in a dose-dependent manner and inhibits cell cycle progression, increasing the proportion of cells in the G0 G1 phase, in both neuroblastoma and pancreatic cancer cells.1,2 Nemorosone (50 mg kg, i.p., per day) also reduces tumor growth in an MIA-PaCa-2 mouse xenograft model.3 References1. Holtrup, F., Bauer, A., Fellenberg, K., et al. Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR). Br. J. Pharmacol. 162(5), 1045-1059 (2011).2. Díaz-Carballo, D., Malak, S., Bardenheuer, W., et al. Cytotoxic activity of nemorosone in neuroblastoma cells. J. Cell. Mol. Med. 12(6B), 2598-2608 (2008).3. Wold, R.J., Hilger, R.A., Hoheisel, J.D., et al. In vivo activity and pharmacokinetics of nemorosone on pancreatic cancer xenografts. PLoS One 8(9), e74555 (2013).

(±)-ErSO is the racemic form of ErSO. ErSO is a selective anticipatory activator of the unfolded protein response (a-UPR).

ErSO-DFP 是一种预期的未折叠蛋白反应 (a-UPR) 激活剂。ErSO-DFP 能够提高对雌激素受体α+ (ERα+) 癌细胞的选择性，选择性高于 ErSO。ErSO-DFP 具有抗肿瘤作用，能够明显消除小鼠模型中 MCF-7 肿瘤。

Z36 is a novel Bcl-xL inhibitor, upregulating the expression levels of FAM134B, LC3, and Atg9, inducing autophagy along with autophagic cell death, resulting in ER stress and the unfolded protein response (UPR).

BOLD-100 (NKP-1339; IT-139) free base 是一款钌基抗癌药物。作为GRP78应激诱导上调的抑制剂，它破坏内质网(ER)的稳态，从而诱发ER应激和未折叠蛋白反应(UPR)。此外，BOLD-100 free base 干预了内质网应激反应、溶酶体动力学以及细胞自噬(autophagy)间的复杂交互作用。

IRE1α kinase-IN-9（compound 2）为一种有效IRE-1α抑制剂，其平均IC50值小于0.1 μM。该化合物适用于探究未折叠蛋白反应（UPR）及调控IRE1依赖性衰减（RIDD）相关疾病的研究。

Mono-Pt 是第一个通过非 DNA 结合线粒体自噬途径抑制癌细胞的 platinum(II) 复合物。Mono-Pt 通过刺激内质网应激 (ERS) 和激活未折叠蛋白反应 (UPR) 促进癌细胞线粒体自噬 (mitophagy)。

IXA4 是一种高选择性、无毒的 IRE1 XBP1s 激活剂，通过激活 IRE1 来减少 APP 的分泌。它刺激的 IRE1 激活也增强了胰腺功能。