er-stress

Tauroursodeoxycholate sodium (TUDC) is an endoplasmic reticulum (ER) stress inhibitor, used for the treatment of gallstones and liver cirrhosis.

Pranoprofen (Pyranoprofen) (INN) is a non-steroidal anti-inflammatory drug used in ophthalmology.

Lycorine (Narcissine) inhibits protein synthesis and may inhibit ascorbic acid biosynthesis, although studies on the latter are controversial and inconclusive.

α-Lipoic Acid (Alphalipoic acid) inhibits NF-κB-dependent HIV-1 LTR activation. α-Lipoic Acid induces endoplasmic reticulum (ER) stress-mediated apoptosis in hepatoma cells.α-Lipoic Acid is an antioxidant, which is an essential cofactor of mitochondrial enzyme complexes.

TrxR1-IN-B19 (TrxR1 IN B19), a TrxR1 inhibitor, selectively kills gastric cancer cells by a small molecule via targeting TrxR1 and ROS-mediated ER stress activation.

TASIN-1 Hydrochloride (TASIN-1 HCl) is a selective inhibitor of truncated APC that acts by selectively killing colorectal cancer cells that express truncated APC by reducing cellular cholesterol levels and inducing apoptotic cell death through the ER stress ROS JNK signaling in colon cancer cells.

RH01386 is a small molecule that prevents ER stress-induced β cell dysfunction and death, inhibits proapoptotic gene expression, and restores ER stress-impaired glucose-stimulated insulin secretion responses, showing potential for type 2 diabetes treatment.

Telomerase-IN-1 is a telomerase inhibitor (IC50: 0.19 μM). telomerase-IN-1 activates hTERT expression through the endoplasmic reticulum stress (ERS) of the ER overreaction (EOR), which then induces ERS, leading to apoptosis. telomerase-IN-1 leads to inhibition of cell proliferation through the expression of downstream signaling molecules including Telomease-IN-1 has high inhibitory activity against telomerase, high anti-proliferative capacity against SMMC-7721 cells, and no significant toxic effect on human normal hepatocytes. telomerase-IN-1 in xenograft tumor model exhibited antitumor activity.

PR-619 (2,6-Diamino-3,5-dithiocyanopyridine) is a DUB inhibitor that inhibits USP2 4 5 7 8 (EC50=7.2 3.93 8.61 6.86 4.9 μM). PR-619 induces endoplasmic reticulum stress and activates autophagy.

Ceapin-A7, with an IC50 of 0.59 μM, selectively inhibits ATF6α signaling in response to ER stress. This compound is instrumental in investigating ATF6α's activation mechanism and its function in pathological conditions.

IRE1α kinase-IN-1 is a highly selective IRE1α (ERN1) inhibitor, with an IC50 of 77 nM, displaying 100-fold selectivity over the IRE1β isoform. It inhibits ER stress-induced IRE1α oligomerization and autophosphorylation, as well as IRE1α RNase activity (IC50=80 nM).

Narasin (sodium salt) (HainanMycin) induces tumor necrosis factor-related apoptosis-induced ligand (TRAIL)-mediated apoptosis by ER stress in glioma cells and inhibits NF-κB signaling by suppressing the phosphorylation of IκBα.

YUM70 is a potent and selective inhibitor of glucose-regulated protein 78 (GRP78), with an IC50 of 1.5 μM for inhibiting GRP78 ATPase activity of the full-length protein. It induces endoplasmic reticulum (ER) stress-mediated apoptosis in pancreatic cancer.

GSK621 is a specific and potent AMPK activator.

Nur77 modulator 1 is an effective Nur77 binder (KD = 3.58 μM) that up-regulates Nur77 expression, mediates its sub-cellular localization, induces Nur77-dependent ER stress and autophagy, and leads to cell apoptosis, demonstrating anti-hepatoma activity.

RH01687 is a potent β-cell protector , exhibits β-cell-protective activities against endoplasmic reticulum (ER) stress.

(E)-2-(2-Chlorostyryl)-3,5,6-trimethylpyrazine (CSTMP) is a stilbene derivative with antioxidant and anticancer activities. It stimulates proliferation of hydrogen peroxide-damaged ECV-304 cells (EC50 = 24.9 nM). CSTMP reduces hydrogen peroxide-induced release of lactate dehydrogenase (LDH) in and increases viability of human umbilical vein endothelial cells (HUVECs) in a concentration-dependent manner via inhibition of apoptosis. It reverses hydrogen peroxide-induced release of malondialdehyde (MDA) and decreases in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities as well as increases constitutive nitric oxide synthase (cNOS) activity and nitric oxide (NO) production in HUVECs. CSTMP also induces cell death of A549 non-small cell lung cancer (NSCLC) cells in an IRE1α-dependent manner through induction of IRE1α-TRAF2-ASK1 complex-mediated endoplasmic reticulum (ER) stress and mitochondrial apoptosis.

Demethylcantharidate disodium, an endogenous metabolite, demonstrates significant anticancer efficacy against various cancers by inducing apoptosis in hepatocellular carcinoma cells through endoplasmic reticulum (ER) stress [1].

Cristacarpin exhibits moderate but selective activity towards DNA repair-deficient yeast mutants. It promotes endoplasmic reticulum (ER) stress, leading to sub-lethal reactive oxygen species (ROS) generation and which eventually terminates by triggering s

Delphinidin-3-O-galactoside chloride has anti-obesity and hypolipidemic effects. Delphinidin-3-O-galactoside (D3G) is a water-soluble anthocyanin with antioxidant activity. D3G is capable of masking the EGCG-induced cytotoxicity and ER stress, presumably

Timosaponin AIII (Timosaponin A3) induces autophagy in HeLa cells followed by apoptotic cell death (IC50: 10 μM). The Timosaponin AIII cellular response is mediated via inhibition of mTORC1 and induction of ER stress (IC50: 2.5 μM, BT474 cells; 6 μM, MDAMB231). The Timosaponin AIII pro-apoptotic response is selective for tumor cells over normal cells but autophagy is induced in both.

CD31, also known as platelet endothelial cell adhesion molecule-1 (PECAM-1), is a receptor on endothelial cells for clostridium perfringens beta-Toxin (CPB). It also functions as an ER-MP12 antigen and connects mechanical stress, metabolism, and inflammation. The CD31 peptide promotes phosphorylation of CD31 ITIM 686 and SHP2, thereby inhibiting TCR-induced T-cell activation [1]-[5].

Vasonatrin Peptide (VNP) TFA, a chimeric compound derived from atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP), exhibits venodilating properties reminiscent of CNP, natriuretic effects akin to ANP, as well as unique arterial vasodilating capabilities not characteristic of either parent peptide. Additionally, VNP TFA confers cardioprotection in diabetic ischemia-reperfusion injury by attenuating endoplasmic reticulum (ER) stress through the cGMP-PKG signaling cascade [1] [2] [3].

KUS121 is a valosin-containing protein (VCP) modulator that inhibits VCP ATPase activity (IC50= 330 nM).1It inhibits cell death, ATP depletion, and upregulation of C/EBP-homologous protein (CHOP) induced by tunicamycin, an inducer of ER stress, in HeLa cells when used at concentrations of 20, 50, and 50 μM, respectively. KUS121 (100 μM) inhibits ATP depletion and cell death induced by oxygen-glucose deprivation (OGD) in rat primary cortical neurons in anin vitromodel of cerebral ischemia.2It reduces infarction volume and increases the latency to fall in an accelerating rotarod test in a mouse model of focal cerebral ischemia induced by transient distal middle cerebral artery occlusion (MCAO) when administered at a dose of 100 mg/kg immediately following occlusion and again at 50 mg/kg following reperfusion. KUS121 (50 mg/kg) inhibits thinning of the retinal outer nuclear layer and preserves visual function in an rd10 mouse model of retinitis pigmentosa.1 1.Ikeda, H.O., Sasaoka, N., Koike, M., et al.Novel VCP modulators mitigate major pathologies of rd10, a mouse model of retinitis pigmentosaSci. Rep.45970(2014) 2.Kinoshita, H., Maki, T., Yasuda, K., et al.KUS121, a valosin-containing protein modulator, attenuates ischemic stroke via preventing ATP depletionSci. Rep.9(1)11519(2019)

Compound 6j (Anticancer agent 147), a sophoridine derivative and ferroptosis inducer, promotes intracellular accumulation of Fe2+, reactive oxygen species (ROS), and malondialdehyde (MDA), enhances endoplasmic reticulum (ER) stress, and upregulates activating transcription factor 3 (ATF3) expression, demonstrating potent anti-liver cancer effects both in vitro and in vivo [1].

1. (+)-(3R,8S)-Falcarindiol is a potential new anticancer agent that exerts its activity through inducing ER stress and apoptosis. 2. Falcarindiol induces immunosuppressive effects in vitro and in vivo and might be a novel therapy for autoimmune or allergic diseases. 3. Falcarindiol has protective effect against CCl(4) toxicity , in part, be explained by anti-lipid peroxidation activity associated with the induction of the GSTs including GSTA4.

BOLD-100 free base (NKP-1339; IT-139), a ruthenium-based anticancer agent, inhibits stress-induced GRP78 upregulation, thus disrupting endoplasmic reticulum (ER) homeostasis. This action induces ER stress and unfolded protein response (UPR), interfering with the intricate relationship between ER-stress response, lysosome dynamics, and autophagy execution.

β-Apopicropodophyllin, a natural product isolated from Hyptis wticillata, promotes apoptosis through mechanisms including microtubule disruption, DNA damage, cell cycle arrest, and ER stress. This compound holds potential for cancer research applications [1].

Soluble epoxide hydrolase (sEH) PROTAC 1a is a proteolysis-targeting chimera (PROTAC) comprising a cereblon ligand linked to the sEH inhibitor t-TUCB via a linker, promoting selective sEH degradation and inhibiting its hydrolase activity (IC50 = 0.8 nM) significantly more than its phosphatase activity (IC50 = >10,000 nM). This compound preferentially targets cytosolic sEH for lysosomal rather than proteasomal degradation. Furthermore, it mitigates thapsigargin-induced upregulation of phosphorylated inositol-requiring enzyme 1α (IRE1α) and X-box binding protein 1 (XBP1) splicing in HepG2 and 293T cells, thereby reducing endoplasmic reticulum stress.

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).

TTA-Q6, a selective T-type Ca2+ channel antagonist, exhibits potential antitumor and immunomodulatory activities for treating neurological disorders by inhibiting the uptake of extracellular calcium ions by tumor cells, thereby inducing intracellular calcium deficiency and endoplasmic reticulum (ER) stress.

α-Lipoic Acid (Thioctic acid) sodium, an essential cofactor for mitochondrial enzyme complexes, functions as an antioxidant. It suppresses NF-κB-dependent activation of HIV-1 LTR [1] [2] [3] and induces ER (endoplasmic reticulum) stress-mediated apoptosis in hepatoma cells [4]. Furthermore, when combined with CPUL1 to form the self-assembled nanoaggregate CPUL1-LA NA, α-Lipoic Acid sodium enhances antitumor efficacy compared to CPUL1 alone [5].

Z-LEVD-FMK, a cell-permeable caspase-4 inhibitor, effectively blocks endoplasmic reticulum (ER) stress-induced apoptosis in cancer cells.

Endoplasmic reticulum (ER) stress, caused by accumulation of misfolded proteins and a disruption of calcium homeostasis, has been linked to several neuronal diseases including, Parkinson's, Alzheimer's, and prion diseases. A screen for protective activity against ER stress-dependent cell death identified termitomycamides, extracts from the fruiting bodies of T. titanicus, a notably large edible mushroom that is cultivated symbiotically in the nests of termites Termitomycamide B is a fatty acid isolated from T. titanicus that at a dose of 0.1 μg/ml protects against ER stress-dependent cell death in Neuro2a cells induced by tunicamycin.

CD31 TFA, also known as platelet endothelial cell adhesion molecule-1 (PECAM-1), functions as the specific receptor for Clostridium perfringens beta-Toxin (CPB) in endothelial cells. It is recognized as an ER-MP12 antigen and plays a pivotal role in connecting mechanical stress, metabolism, and inflammation. Additionally, the CD31 TFA peptide facilitates the phosphorylation of CD31 ITIM 686 and SHP2, further inhibiting TCR-induced T-cell activation [1]-[5].

KM10103 exhibits β-cell-protective activities against ER stress, which plays an important role in the decline in pancreatic β cell function and mass observed in type 2 diabetes.

Acetylshikonin can effectively inhibit tumor cells, it can be used to treat hepatocellular carcinoma cells expressing hepatitis B virus X protein (HBX) by inducing ER stress , an oncoprotein from hepatitis B virus. Acetylshikonin inhibits the production of eicosanoid, is due to the attenuation of cytosolic phospholipase A(2) membrane recruitment via the decrease in [Ca(2+)](i) and to the blockade of cyclooxygenase and 5-lipoxygenase activity.

ERX-41 is an orally active, stereospecific small molecule that targets lysosomal acid lipase A (LIPA). It induces endoplasmic reticulum (ER) stress, leading to cell death independently of its LIPA activity yet reliant on its ER localization, suggesting a role in targeted solid tumor therapies [1].

SLMP53-2 is a mutant p53 reactivator that restores the wild-type-like conformation and DNA-binding ability of mutp53-Y220C through enhanced interaction with Hsp70, thereby reinstating p53's transcriptional activity. This compound induces cell cycle arrest, apoptosis, and endoplasmic reticulum (ER) stress, displaying antitumor activity [1] [2].

NE-100 hydrochloride (NE-100 HCl) is a potent and selective antagonist of σ1 (IC50 = 4.16 nM) with antipsychotic activity. NE100 HCl also suppresses ER stress-induced hippocampal cell death.

Cefatrizine is an inhibitor of eukaryotic elongation factor-2 kinase, a unique calcium/calmodulin-dependent protein kinase, is well known to regulate apoptosis, autophagy and ER stress in many types of human cancers.

ABTL-0812 induces endoplasmic reticulum (ER) stress-mediated autophagy, and with anti-cancer activity.