unfolded protein response

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。

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。

Azoramide 是一种小分子调节剂，具有未折叠蛋白反应的抗糖尿病活性。

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。

Thapsigargin 属于天然产物，是一种肌 内质网 Ca2+ ATP 酶 (SERCA) 的抑制剂，也是一种内质网应激诱导剂。Thapsigargin 通过阻断细胞将钙泵入肌浆和内质网的能力来提高胞浆钙浓度。

CCI-006 是一种 MLL 重排白血病细胞的选择性抑制剂和化学增敏剂。 它能够抑制线粒体呼吸，造成 MLL-r 白血病细胞亚群中无法克服的线粒体去极化和促凋亡未折叠蛋白反应。

RA-9 是一种高选择性蛋白酶体相关的 DUBs 抑制剂，具有良好的毒性和抗癌活性。它阻断泛素依赖性蛋白降解而不影响 20S 蛋白酶体蛋白水解活性。它诱导卵巢癌细胞内质网应激反应，选择性诱导卵巢癌细胞株和供体原代培养细胞凋亡。

3,6-DMAD hydrochloride is an inhibitor of the IRE1α-XBP1 pathway of the unfolded protein response.

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.

DIM-C-pPhtBu是一种口服有效的内质网应激激活剂。它在颈部癌细胞中引发线粒体和溶酶体功能障碍、过度有丝分裂、ROS产生，以及因未折叠蛋白反应引起的细胞死亡。DIM-C-pPhtBu展现出抗肿瘤活性。

Autophagyactivator-1 (Compound B2) 是一种通过下调关键的HSP70家族成员并激活未折叠蛋白反应来促进自噬的自噬激活剂。

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-8，作为苯并杂环甲醛衍生物，是一种高效的IRE-1α抑制剂，主要用于研究未折叠蛋白反应或受调节的IRE1依赖性衰减(RIDD)相关疾病。

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)。

DTX-P7 是一种由 Docetaxel (DTX) 和一个七肽 (P7) 组成的多肽药物偶联物 (PDC)，通过破坏 Hsp90 蛋白，诱导未折叠蛋白反应，进而导致细胞凋亡。