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。

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)。

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。

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。

Mycothiazole 是一种线粒体电子传递链 (ETC) 复合物 I 的抑制剂，在癌细胞 Huh7 (IC50为 55.8 μM)、U87 和 MCF7 中展现出细胞毒性，并在 Huh7 中诱导细胞凋亡 (apoptosis)。它通过调节未折叠蛋白反应 (UPR) 和热休克反应 (HSR) 相关的转录因子 ATFS-1 和 HSF1，延长 C. elegans 的寿命。