4SC 301 / 4SC - LARVOL DELTA

Qingda granule prevents Ang II-induced cardiac hypertrophy via inhibiting NF-κB signaling pathway. (PubMed, Front Pharmacol) - "QDG also inhibited Ang II-induced adverse NF-κB signaling activation and downstream pro-inflammatory targets, which were prevented via administration with SC75741, a specific NF-κB inhibitor. Our findings provide further insight into the robust ability of QDG in preventing Ang II-induced cardiac hypertrophy via preventing NF-κB signaling activation and implicate its use in the clinical treatment of hypertension and cardiac hypertrophy."

Journal • Cardiovascular • Hypertension

E2 pretreatment alleviates aggregation of intravenously injected mesenchymal stem cells in TBI by regulating BRG1 to affect adhesion. (PubMed, Stem Cell Res Ther) - "Our study proposes the inflammatory state after TBI leads to enhanced adhesion of blood vessels and transplanted stem cells, which is a contributing factor to the increased aggregation of intravenous hUMSCs in the lungs, E2 can alleviate pulmonary aggregation in stem cell intravenous injection therapy."

Journal • Inflammation • Transplantation • SMARCA4 • TNFA

Integrated transcriptomics and metabolomics confirms the oxidative stress mechanism of hypothermia-induced neuronal necroptosis. (PubMed, Cell Mol Biol Lett) - "Pharmacological inhibition of NF-κB by the SC75741 inhibitor effectively ameliorated hypothermia-triggered necroptosis. In conclusion, our results suggest that the NF-κB transcription factor is a potential marker of hypothermia-induced neuronal necroptosis in the mouse cerebral cortex. In addition, our findings indicate the mechanism of necroptosis in cerebral cortical neurons caused by low temperature, which is beneficial for our understanding of hypothermia-induced coma and death."

Journal • Oncology • TNFA

Immunodynamic axis of fibroblast-driven neutrophil infiltration in acute pancreatitis: NF-κB-HIF-1α-CXCL1. (PubMed, Cell Mol Biol Lett) - "This study, for the first time, demonstrated that activation of fibroblasts is one of the immunological driving factors for neutrophil infiltration and elucidated that glycolysis driven by the NF-κB-HIF-1α pathway is the intrinsic molecular mechanism by which fibroblasts secrete CXCL1 to chemotactically attract neutrophils. This finding provides a highly promising target for the treatment of AP."

Journal • Inflammation • Pancreatitis • CXCL1 • CXCR2 • HIF1A

β-Hydroxybutyrate aggravates LPS-induced inflammatory response in bovine endometrial epithelial cells by activating the oxidative stress/NF-κB signaling pathway. (PubMed, Int Immunopharmacol) - "As a representative antioxidant, N-acetylcysteine (NAC) treatment significantly reduced the phosphorylation of p65 and IκB in the BHBA and LPS co-treatment group...In summary, the current study demonstrates that BHBA aggravates LPS-induced inflammatory response in BENDs through the activation of oxidative stress/NF-κB signaling pathway, unravelling the mechanism by which BHBA exacerbates the inflammatory response in the BENDs of dairy cattle. This study elucidates the role of ketosis and its key metabolite BHBA in the pathogenesis of endometritis in dairy cows, providing valuable insights for understanding this pathological process."

Journal • Endometriosis • Inflammation • Metabolic Disorders • CAT • CXCL8 • HMOX1 • IL1B • IL6

IL-6 upregulates the expression of human placental MSC SPP1 through the NF-κB signaling pathway and promotes M2 macrophage polarization (PubMed, Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi) - "Results IL-6 significantly upregulates the expression of SPP1 in protein and mRNA levels in hfPMSCs; interference of SPP1 significantly downregulates the expression of SPP1 in hfPMSCs and significantly reduces the positive cell ratio of CD206 in co-cultured macrophages; IL-6 significantly upregulates the expression of p-p65 in hfPMSCs, activating the NF-κB signaling pathway; SC75741 significantly downregulates the expression of p-p65 and SPP1 in hfPMSCs treated with IL-6. Conclusion IL-6 upregulates the expression of SPP1 through the NF-κB signaling pathway in hfPMSCs, which enhances the capability to induce macrophages to polarize towards the M2 phenotype."

Journal • CD14 • CD34 • CD73 • ENG • IL6 • ITGAX • MRC1 • PTPRC • RELA • SPP1 • THY1

Mitochondrial ROS participates in Porphyromonas gingivalis-induced pyroptosis in cementoblasts. (PubMed, Heliyon) - "Together, our findings demonstrate that mitochondrial reactive oxygen species increased by Porphyromonas gingivalis participated in the pyroptosis of cementoblasts. Targeting mitochondrial reactive oxygen species may offer therapeutic strategies for root surface remodeling or periodontal regeneration."

Journal

Repositioning of anti-infective compounds against monkeypox virus core cysteine proteinase: a molecular dynamics study. (PubMed, Mol Divers) - "The overall RMSD suggested that two compounds, SC75741 and ammonium glycyrrhizinate, showed a highly stable complex with a standard deviation of 0.18 and 0.23 nm, respectively. Later, the MM/GBSA binding free energies of complexes showed significant binding strength with ΔGTOTAL from -21.59 to -15 kcal/mol. This report reported the potential inhibitory activity of SC75741 and ammonium glycyrrhizinate against MPXV-CCP by competitively inhibiting the binding of the native substrate."

Journal • Infectious Disease

Shen-Shuai-II-Recipe inhibits tubular inflammation by PPARα-mediated fatty acid oxidation to attenuate fibroblast activation in fibrotic kidneys. (PubMed, Phytomedicine) - "SSR inhibits RIF by suppressing inflammatory response of hypoxia-exposed RTECs through PPARα-mediated FAO."

Journal • Chronic Kidney Disease • Fibrosis • Immunology • Inflammation • Nephrology • Renal Disease • IL18 • NLRP3 • PPARA

In silico molecular study of hepatitis B virus X protein as a therapeutic target. (PubMed, J Biomol Struct Dyn) - "The analysis of relative binding free energy through MM/GBSA for molecular dynamic simulation results revealed binding energy -9.9 kcal/mol for SC75741, -11 kcal/mol for Punicalagin, and -10.1 kcal/mol for Ledipasvir. These results elucidate the possible use of these compounds in the research for targeting HBx.Communicated by Ramaswamy H. Sarma."

Journal • Fibrosis • Gastroenterology • Gastrointestinal Cancer • Hepatitis B • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis • Oncology • Solid Tumor

Induction of apoptosis in glioma cells by lycorine via reactive oxygen species generation and regulation of NF-κB pathways. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "The addition of NF-κB inhibitor SC75741 further confirmed the importance of the NF-κB pathway in lycorine-induced cell-growth inhibition. Moreover, lycorine might act synergically with temozolomide (TMZ) to reduce drug resistance by blocking the NF-κB pathway. Our study suggested that lycorine exerts an anti-glioma effect by inducing ROS production and inhibiting NF-κB, which validated that lycorine may be a potential candidate for glioma treatment alone or in combination with TMZ."

Journal • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • NF-κβ

Tanshinone IIa attenuates vascular calcification through inhibition of NF-κB and β-catenin signaling pathways (PubMed, Sheng Li Xue Bao) - "Similar to Tanshinone IIa, inhibition of NF-κB and β-catenin signaling using the chemical inhibitors SC75741 and LF3 attenuated high phosphate-induced vascular smooth muscle cell calcification. These results suggest that Tanshinone IIa attenuates vascular calcification at least in part through inhibition of NF-κB and β-catenin signaling, and Tanshinone IIa may be a potential drug for the treatment of vascular calcification."

Journal • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Dyslipidemia • Hypertension • Metabolic Disorders • Nephrology • Renal Disease

Mechanism of RIP2 enhancing stemness of glioma cells induces temozolomide resistance. (PubMed, CNS Neurosci Ther) - "RIP2 mediates TMZ resistance by regulating the maintenance of stemness in glioma cells through NF-κB. Interventions targeting the RIP2/NF-κB pathway may be a new strategy for TMZ-resistant gliomas."

Journal • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • CD133 • NFKBIA • RIPK2 • SOX2

The short-chain fatty acid butyrate accelerates vascular calcification via regulation of histone deacetylases and NF-κB signaling. (PubMed, Vascul Pharmacol) - "Intriguingly, the NF-κB inhibitor SC75741 significantly attenuated butyrate-induced calcification and the osteogenic gene Msx2 expression in VSMCs...This study reveals that butyrate accelerates vascular calcification via its dual effects on HDAC inhibition and NF-κB activation. Our data provide novel insights into the role of microbe-host interaction in vascular calcification, and may have implications for the development of potential therapy for vascular calcification."

Epigenetic controller • Journal • Cardiovascular

Melatonin Inhibits NF-κB/CREB/Runx2 Signaling and Alleviates Aortic Valve Calcification. (PubMed, Front Cardiovasc Med) - "Besides, the NF-κB inhibitor (SC75741) reduced OST medium-induced VIC calcification to a similar extent to melatonin at 10 nmol/L...Activation of the melatonin/MT1-axis significantly reduced VIC calcification by targeting the NF-κB/CREB/Runx2 pathway. Targeting melatonin/MT1 signaling may be a potential therapeutic strategy for CAVD."

Journal • RUNX2

Protective effects of three flavonoids from Dendrobium huoshanense flowers on alcohol-induced hepatocyte injury via activating Nrf2 and inhibiting NF-κB pathways. (PubMed, Chem Biodivers) - "Flavonoids 1 - 3 could also reduce the phosphorylation levels of I κ B α and NF- κ B p65 of alcohol-induced L02 cells, while SC75741 (NF- κ B inhibitor) could not enhance the inhibitory effects of 1 - 3 on alcohol-induced L02 cells injury. The data above indicated that flavonoids 1 - 3 could inhibit alcohol-induced hepatocyte injury, which might be attributed to alleviating oxidative stress and mitigating inflammatory response by activating Nrf2 and inhibiting NF- κ B pathways."

Journal • Immunology • Inflammation • RELA

Promising antivirals for PLpro of SARS-CoV-2 using virtual screening, molecular docking, dynamics, and MMPBSA. (PubMed, J Biomol Struct Dyn) - "Molecular docking results suggested that five molecules (44560613, 136277567, S5652, SC75741, and S3833) had good binding affinities at both sites of PLpro...Molecular Mechanics/Position-Boltzmann Surface Area (MMPBSA) analysis confirmed that antiviral molecules bound PLpro complex had lower energy (-184.72 ± 7.81 to -215.67 ± 6.73 kJ/mol) complexes. Noticeably, computational approaches revealed promising antivirals candidates for PLpro, which may be further tested by biochemical and cell-based assays to assess their potential for SARS-CoV-2.Communicated by Ramaswamy H. Sarma."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Comparative Transcriptomic Analysis Reveals That HSP90AB1 Is Involved in the Immune and Inflammatory Responses to Porcine Deltacoronavirus Infection. (PubMed, Int J Mol Sci) - "The DEGs enriched in NF-κB pathways were specifically detected in HSP90AB1 cells, and NF-κB inhibitors JSH-23, SC75741 and QNZ treatment reduced PDCoV infection...Knockout of HSP90AB1 altered the upregulated levels of some cytokines. Taken together, our findings provide new insights into the host response to PDCoV infection from the transcriptome perspective, which will contribute to illustrating the molecular basis of the interaction between PDCoV and HSP90AB1."

Journal • Preclinical • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • HSP90AA1 • KEAP1

SC75741, A Novel c-Abl Inhibitor, Promotes the Clearance of TDP25 Aggregates via ATG5-Dependent Autophagy Pathway. (PubMed, Front Pharmacol) - "Taken together, these findings show that SC75741 has beneficial neuroprotective effects in ALS. Our study elucidates that dual-targeted inhibition of c-Abl and NF-κB may be a potential treatment for TDP43 proteinopathies and ALS."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Immunology • Inflammation • Proteinopathy • ABL1 • ATG5 • TARDBP • TFEB

Novel NFκB Inhibitor SC75741 Mitigates Chondrocyte Degradation and Prevents Activated Fibroblast Transformation by Modulating miR-21/GDF-5/SOX5 Signaling. (PubMed, Int J Mol Sci) - "Interestingly, in vivo study demonstrated SC75741 protective role, in controlling the destruction of the articular joint, through NFκB, TNF-α, IL-6, and miR-21 inhibition, and inducing GDF-5, SOX5, TGF-β1, BMPR2, and COL4A1 expression. Our study demonstrated the role of NFκB/miR-21 axis in OA progression, and SC75741's therapeutic potential as a small-molecule inhibitor of miR-21/NFκB-driven OA progression."

Journal • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology • Collagen Type IV • IL6 • MIR21 • TGFB1 • TNFA

SC75741 antagonizes vesicular stomatitis virus, duck Tembusu virus, and duck plague virus infection in duck cells through promoting innate immune responses. (PubMed, Poult Sci) - "In addition, SC75741 enhanced the expression of interferon only when stimulator of interferon genes (STING) was overexpressed or pre-activated by the virus infection, suggesting that SC75741 acts as a STING agonist. In conclusion, SC75741 is a candidate antiviral agent for DTMUV and DPV."

Journal • Infectious Disease • STING

S100A9 induces nucleus pulposus cell degeneration through activation of the NF-κB signaling pathway. (PubMed, J Cell Mol Med) - "The detailed mechanism underlying S100A9-induced NP degeneration was explored by administering SC75741, a specific NF-κB inhibitor in vitro. We concluded that S100A9 induced NP cell apoptosis, caused matrix degradation and amplified the inflammatory response through the activation of the NF-κB signalling pathway. Inhibition of these pro-apoptotic, pro-degradation and pro-inflammatory effects induced by S100A9 in NP may be a favourable therapeutic strategy to slow lumbar disc degeneration."

Journal • Inflammation • CASP3 • S100A9

The NF-κB inhibitor, SC75741, is a novel antiviral against emerging tick-borne bandaviruses. (PubMed, Antiviral Res) - "We demonstrated that the NF-κB inhibitor, SC75741, reduces viral RNA synthesis of SFTSV and HRTV using our MG platform and validated these results using infectious SFTSV and HRTV. These results may lead to the use of MG systems as potential screening systems for the identification of antiviral compounds and yield novel insights into host-factors that could play role in bandavirus transcription and replication."

Journal • Hematological Disorders • Inflammation • Thrombocytopenia

Effect of Eriocalyxin B on prostatic inflammation and pelvic pain in a mouse model of experimental autoimmune prostatitis. (PubMed, Prostate) - "The results of the present study suggested that EriB could alleviate the severity of prostatic inflammation and pelvic pain in an EAP mouse model. These findings may broaden the value of EriB as a promising candidate for the treatment of CP/CPPS."

Journal • Preclinical • Gynecology • Immunology • Inflammation • Musculoskeletal Pain • Obesity • Oncology • Pain

Nuclear Factor-κB Overexpression is Correlated with Poor Outcomes after Multimodality Bladder-Preserving Therapy in Patients with Muscle-Invasive Bladder Cancer. (PubMed, J Clin Med) - "Irradiated bladder cancer cells showed increased invasion capability and clonogenic survival; inhibition of NFκB signaling by an NFκB inhibitor, SC75741, or RNA interference reversed the observed increases. NFκB expression (p65) is associated with prognostic significance for both LPFS and DMFS in patients treated with bladder-preserving therapy, with consistent impact on cell viability of bladder cancer cells. NFκB may be a putative molecular target to help with outcome stratification."

Clinical • IO Biomarker • Journal • CDH1 • HER2 • MLH1 • MMP9 • MRE11A • MSH2 • MSH6 • PD-L1 • PMS2