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DRUG CLASS:

eIF2α dephosphorylation inhibitor

2ms
Single-cell and transcriptomic profiling reveal stemness-driven immune evasion in obstructive sleep apnea (OSA) associated lung cancer. (PubMed, J Cancer)
Drug sensitivity analyses further suggested that stemness-high tumors may exhibit increased susceptibility to selected kinase inhibitors (Dasatinib, A-770041) and metabolic modulators (Phenformin, Salubrinal). OSA-associated IH is linked to stemness-associated transcriptional plasticity, immune suppression, and adverse clinical outcomes in lung cancer. The identified stemness-based gene signature provides a robust prognostic biomarker and highlights potential therapeutic vulnerabilities, supporting integrative strategies that combine stemness and immune -targeted approaches with immunotherapy in OSA-associated lung cancer.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • PD-1 (Programmed cell death 1) • LAG3 (Lymphocyte Activating 3) • MELTF (Melanotransferrin)
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dasatinib • salubrinal
2ms
Novel mtDNA methylation-associated prognostic signatures in colorectal cancer. (PubMed, Front Oncol)
Sorafenib, Salubrinal, and Roscovitine were positively correlated with the risk score, whereas WO2009093972 was negatively correlated. Additionally, this study identified several target genes such as FBXO25 with TINAG, CCDC28A with EPHB2, and SH2D6 with FCN3, with subsequent validation achieved through qPCR and western blotting. In conclusion, this study identifies three prognostic genes, providing new insights into CRC pathogenesis and potential therapeutic strategies.
Journal
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EPHB2 (EPH Receptor B2)
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sorafenib • salubrinal • seliciclib (CYC202)
5ms
Rutin Suppresses EMT and Induces Mitochondrial Biogenesis via ER Stress-linked AMPK/SIRT1 Signaling in Prostate Cancer Cells. (PubMed, Cancer Genomics Proteomics)
Rutin inhibits prostate cancer progression by suppressing EMT, inducing mitochondrial biogenesis, and acting via ER stress-linked AMPK/SIRT1 signaling. These findings suggest that Rutin may serve as a potential therapeutic candidate for advanced prostate cancer.
Journal
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CDH1 (Cadherin 1) • NRF1 (Nuclear Respiratory Factor 1) • ATF6 (Activating Transcription Factor 6) • ERN1 (Endoplasmic Reticulum To Nucleus Signaling 1) • SNAI2 (Snail Family Transcriptional Repressor 2) • TFAM (Transcription Factor A, Mitochondrial)
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salubrinal
over1year
Polyamine-modified naphthalimide derivative 9C inhibits colorectal cancer through ROS-mediated ER stress, migration and invasion. (PubMed, Toxicol In Vitro)
Pretreatment of ER stress inhibitor, such as salubrinal, and autophagy inhibitor, such as 3-methyladenine (3-MA), partially reversed 9C-induced inhibition of cell growth...Removal of ROS using N-acetyl-L-cysteine (NAC) attenuated the expression of ATF4, CHOP, death receptors, E-cadherin, and the apoptosis and autophagy related proteins. Taken together, our results suggested that ROS-mediated ER stress, migration, and invasion is responsible for the therapeutic potential of naphthalimides including 9C in CRC.
Journal
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CDH1 (Cadherin 1) • ATF4 (Activating Transcription Factor 4)
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CDH1 expression
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salubrinal
over1year
Dissecting the Implications of Calumenin in Malignancy and Heterogeneity of the Microenvironment of Clear Cell Renal Cell Carcinoma Using Multi-Omics Data. (PubMed, Phenomics)
Sensitivity analysis of common chemotherapeutic drugs showed that high expression of CALU could sensitize chemotherapeutic drugs such as 5Z-7-Oxozeaenol, AMG-706 and Cytarabine, but could lead to drug resistance to chemotherapeutic drugs such as Embelin, Salubrinal and Tipifarnib. Thus, our results indicate that CALU could be a biomarker and designing personalized treatment approaches for ccRCC patients. The online version contains supplementary material available at 10.1007/s43657-024-00169-7.
Journal • IO biomarker
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CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
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cytarabine • Zarnestra (tipifarnib) • motesanib (AMG 706) • salubrinal
over1year
Integrated stress response-upregulated mitochondrial SLC1A5var enhances glucose dependency in human breast cancer cells in vitro. (PubMed, Int J Biochem Cell Biol)
Glucose depletion-, oligomycin-, and salubrinal-activated activating transcription factor-4 (ATF4) induced SLC1A5var expression...These results suggest that activated ISR-induced increased expression of SLC1A5var may regulate mitochondrial oxidative phosphorylation and glycolytic metabolic characteristics to enhance glucose depletion-induced cell death. In conclusion, SLC1A5var plays a vital role in metabolic reprogramming and may be a potential target for breast cancer treatment.
Preclinical • Journal
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SLC1A5 (Solute Carrier Family 1 Member 5) • SLC7A11 (Solute Carrier Family 7 Member 11) • ATF4 (Activating Transcription Factor 4) • TCF4 (Transcription Factor 4)
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SLC1A5 overexpression • SLC1A5 expression
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salubrinal
over1year
Regulation of Hepatitis B Virus Replication by Modulating Endoplasmic Reticulum Stress (ER-Stress). (PubMed, Int J Microbiol)
Here, we investigated the viral protein expression, replication, and virion production using endoplasmic reticulum (ER) stress-modulating chemicals, tunicamycin (an ER-stress inducer), and salubrinal (an ER-stress inhibitor)...In conclusion, the sal-mediated inhibition of the HBV replication and virion production might be due to the simultaneous reduction of core and large HBsAg expression and maintaining the ER homeostasis. These results of HBV replication regulation by modulation of ER-stress dynamics would be useful for designing/identifying anti-HBV drugs targeting cellular signaling pathways.
Journal
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HSPA5 (Heat Shock Protein Family A (Hsp70) Member 5)
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salubrinal
over1year
"Investigation of the Potential Cellular Changes Induced by Magnesium Sulfate and Salubrinal in a Lipopolysaccharide-Induced Chorioamnionitis Model". (PubMed, Eur J Pharmacol)
The known anti-inflammatory activity of Mg, when used with SLB, preventing the transition to apoptosis and increasing antioxidant enzyme activity, as identified in this study, can contribute significantly to the literature. However, these results need to be supported by additional molecular studies.
Journal • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • TNFA (Tumor Necrosis Factor-Alpha) • BAX (BCL2-associated X protein) • CASP3 (Caspase 3) • GFAP (Glial Fibrillary Acidic Protein)
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salubrinal
2years
Novel insight on IRE1 in the regulation of chondrocyte dedifferentiation through ER stress independent pathway. (PubMed, J Physiol Biochem)
In response to various endoplasmic reticulum (ER) agonists (2-deoxy-D-glucose), and ER stress antagonists (tauroursodeoxycholic acid and salubrinal), IRE1 overexpression did not affect GRP78/94, as implicated in the pathogenesis of ER stress. Moreover, when IRE1 overexpression was correlated with the inflammation pathway, nuclear factor-kappa B (NFκB), IRE1 substantially increased the expression of p50 while decreasing the expression of nuclear factor kappa light polypeptide alpha (IκBα). These results suggest that IRE1 induces dedifferentiation in chondrocytes by modulating inflammatory pathways that cause dedifferentiation by disrupting type II collagen expression.
Journal
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HSPA5 (Heat Shock Protein Family A (Hsp70) Member 5) • ERN1 (Endoplasmic Reticulum To Nucleus Signaling 1) • NFKBIA (NFKB Inhibitor Alpha 2)
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salubrinal
2years
A Five-gene Signature Based on MicroRNA for Predicting Prognosis and Immunotherapy in Stomach Adenocarcinoma. (PubMed, Curr Med Chem)
This study promotes the underlying mechanisms of miRNA-based genes in STAD and offers directions for classification. A five-gene signature accurately predicts the prognosis and helps therapeutic options.
Journal • Tumor mutational burden • Gene Signature • IO biomarker
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TMB (Tumor Mutational Burden)
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TMB-L
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gemcitabine • sorafenib • vinorelbine tartrate • salubrinal
over2years
Cuproptosis-related signature for clinical prognosis and immunotherapy sensitivity in hepatocellular carcinoma. (PubMed, J Cancer Res Clin Oncol)
Our findings highlight the potential of the CRGs risk score as an independent and promising biomarker for clinical prognosis and immunotherapy sensitivity in HCC patients.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • PD-1 (Programmed cell death 1) • KDR (Kinase insert domain receptor)
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cisplatin • erlotinib • gefitinib • gemcitabine • sorafenib • lapatinib • nilotinib • cyclopamine • salubrinal
over2years
Ischemic preconditioning attenuates endoplasmic reticulum stress-dependent apoptosis of hepatocytes by regulating autophagy in hepatic ischemia-reperfusion injury. (PubMed, Int Immunopharmacol)
The ERS inhibitor salubrinal significantly alleviated liver injury in HIRI and OGD/R hepatocytes. The autophagy inhibitor 3-methyladenine significantly attenuated the protective effects of IPC on ERS-dependent apoptosis and liver function, whereas the autophagy activator rapamycin mimicked the protective effects of IPC on ERS-dependent apoptosis in vivo and in vitro, suggesting a regulatory role of autophagy in ERS-dependent apoptosis. These results demonstrated that IPC could induce moderate autophagy and upregulate a few molecular chaperones to strengthen endogenous defense mechanisms, which is beneficial for alleviating ERS-dependent apoptosis and protecting hepatocytes from HIRI.
Journal
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HSPA5 (Heat Shock Protein Family A (Hsp70) Member 5) • CASP12 (Caspase 12 (Gene/Pseudogene)) • HSPD1 (Heat Shock Protein Family D (Hsp60) Member 1)
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sirolimus • salubrinal