SP600125 / BMS - LARVOL DELTA

Ribes fasciculatum Leaf Water Extract Enhances Macrophage Immune Responses via TLR4-Mediated JNK and NF-κB Activation in RAW264.7 Cells. (PubMed, J Microbiol Biotechnol) - "The immunostimulatory effects of RFL-DW20 were strongly inhibited by TAK-242, SP600125, and BAY 11-7082, suggesting the involvement of TLR4, JNK, and NF-κB signaling. Ethanol precipitation further enriched its NO-inducing activity. These findings suggest that RFL-DW20 activates macrophages through the TLR4/JNK/NF-κB signaling axis and may serve as a natural immune-stimulating material."

Journal • IL1B • IL6 • NFKBIA • PTGS2 • TLR4 • TNFA

Acupuncture Suppresses the ER Stress-JNK Pathway to Inhibit Chondrocyte Apoptosis and Attenuate Knee Osteoarthritis. (PubMed, Cell Stress Chaperones) - "Our findings demonstrate for the first time that acupuncture ameliorates knee osteoarthritis by inhibiting chondrocyte apoptosis via suppression of the ER stress-JNK signaling pathway. This study provides a novel and robust mechanistic rationale for the clinical application of acupuncture and highlights the ER stress-JNK axis as a promising therapeutic target for KOA."

IO biomarker • Journal • Immunology • Osteoarthritis • Pain • Rheumatology • BAX • BCL2 • CASP3 • IL10 • IL1B • MAPK8 • TNFA

Musashi-1 Drives Radioresistance and Stemness in Head and Neck Squamous Cell Carcinoma via a Radioresistant FaDu Model. (PubMed, Cancer Sci) - "JNK inhibition with SP600125 reduced MSI1 levels and attenuated stemness and radioresistance in F-IRR cells. In vivo xenograft experiments further confirmed that F-IRR cells possessed greater tumorigenic potential and radioresistance than parental cells, with high expression of MSI1 and phospho-JNK in tumor tissues. Collectively, these findings identify the JNK-MSI1 axis as a critical driver of CSC-mediated radioresistance in HNSCC and a promising therapeutic target for overcoming treatment failure."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • MAPK8 • MSI1

Eugenol Exhibits Cyclic Nucleotide/VASP-Independent Antiplatelet Activity Associated with Inhibition of Arachidonic Acid-Induced JNK Phosphorylation and Reduces Thrombus Formation as Visualized by Real-Time Intravital Imaging. (PubMed, Biomedicines) - "In vivo, real-time intravital imaging showed that eugenol and SP600125 delayed thrombus formation and prolonged occlusion time. These findings suggest that eugenol exerts inhibitory effects that may involve modulation of JNK phosphorylation, independent of cyclic nucleotide/VASP pathways in AA-induced platelet activation, highlighting its potential as an antithrombotic agent."

Journal • Cardiovascular • Hematological Disorders • Oncology • Thrombosis

Sodium butyrate alleviates neuronal ferroptosis after gas explosion-induced traumatic brain injury via regulation of JNK/P38 MAPK signaling pathway. (PubMed, Eur J Pharmacol) - "Pharmacological inhibition with SP600125 (a JNK inhibitor), SB203580 (a p38 MAPK inhibitor), and ferrostatin-1 (Fer-1, a ferroptosis inhibitor) was employed to confirm pathway involvement...Notably, co-administration of pathway inhibitors potentiated the protective effects of NaB, further corroborating the involvement of JNK/p38 MAPK-mediated ferroptosis in GE-induced TBI. Collectively, these findings indicate that NaB attenuates GE-induced TBI and ferroptosis, likely through inhibition of the JNK/p38 MAPK signaling pathway."

Journal • CNS Disorders • Inflammation • Oncology • Vascular Neurology • GPX4 • IL10 • IL6 • MAPK8 • SLC7A11 • TNFA

Environmentally relevant imidacloprid exposure elicits hippocampal microglial apoptosis via JNK-FOXO3 pathway: Implication for latent central neurotoxicity. (PubMed, J Hazard Mater) - "Consistently, IMI induced apoptosis in BV2 microglial cells through activation of the JNK-FOXO3 signaling pathway, whereas FOXO3 knockdown or JNK inhibition with SP600125 markedly attenuated this effect. These findings indicate that environmentally relevant IMI exposure can trigger hippocampal microglial apoptosis via JNK-FOXO3 signaling even in the absence of overt behavioral deficits, suggesting a potential early neurotoxic effect of neonicotinoid exposure."

IO biomarker • Journal • Alzheimer's Disease • Cognitive Disorders • BCL2

Interleukin-33 enhances ASIC currents in mouse dorsal root ganglion neurons. (PubMed, J Biol Chem) - "The enhancing effect of IL-33 on ASIC currents was prevented by the p38 mitogen-activated protein kinase inhibitor SB202190, but not by the ERK inhibitor U0126 or the JNK inhibitor SP600125, indicating the effect was p38-dependent. Finally, ASIC3-deficient mice displayed attenuated mechanical hyperalgesia induced by intraplantar or intramuscular injection of IL-33. Our findings revealed that IL-33 enhanced ASIC function via ST2 and the intracellular p38 signaling pathway, which might provide a promising therapeutic approach for pain treatment by targeting IL-33/ST2 signaling."

Journal • Preclinical • Oncology • Pain • IL33

β3-AR/β-arrestin2 Interaction Triggers Cardiac Fibrosis Through JNK/c-Jun Pathway in Cardiac Fibroblasts. (PubMed, J Cell Mol Med) - "Primary cardiac fibroblasts were isolated from neonatal C57BL/6 mice and subjected to β3-AR overexpression, agonist (BRL37344) stimulation, antagonist (SR59230A) inhibition, JNK inhibitor (SP600125) treatment, or β-arrestin2 knockdown via siRNA...Our findings demonstrate that β3-AR promotes cardiac fibrosis through β-arrestin2-mediated biased activation of the JNK/c-Jun/TGF-β1 pathway, independent of classical Gi signalling. This study reveals a novel cell-specific signalling mechanism of β3-AR and provides a potential therapeutic target for developing precision drugs against MF and HF."

Journal • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • Infectious Disease • Respiratory Diseases • ARRB1 • TGFB1

Leukotriene B4 potentiates acid-sensing ion channel currents in mouse dorsal root ganglion neurons. (PubMed, Neuropharmacology) - "The LTB4-induced potentiation of ASIC currents was prevented by the ERK1/2 inhibitor U0126 and the JNK inhibitor SP600125, but not by the p38 inhibitor SB202190, indicating involvement of intracellular ERK1/2 and JNK signaling. Behaviorally, intraplantar injection of LTB4 exaggerated spontaneous nociceptive behaviours evoked by subsequent acid challenge in WT mice, and developed attenuated mechanical hyperalgesia in ASIC3 KO mice. Our results suggested that LTB4 potentiated the electrophysiological activity of ASICs via BLT1 receptors as well as the ERK1/2 and JNK signaling pathways, which might open promising new perspectives for pain treatment associated with tissue acidification."

Journal • Preclinical • Pain

IL-17-associated Pro-inflammatory Programs in Aortic Valve Interstitial Cell Osteogenic Differentiation: JUN as a Candidate Regulator. (PubMed, Inflammation) - "In a chronic kidney disease-induced mouse CAVD model, JNK inhibition with SP600125 reduced valve calcification and leaflet thickness. IL-17-associated inflammatory signaling is engaged during VIC osteogenic differentiation and may promote calcification, partially through a JUN-dependent mechanism. These findings provide insight into how inflammatory programs interface with osteogenic transcription and offer a framework for dissecting inflammation-driven calcification in CAVD."

Journal • Cardiovascular • Chronic Kidney Disease • Inflammation • Nephrology • Renal Disease • IL17A • IL17RA

CXCL3 deficiency ameliorates COPD by suppressing cigarette smoke-induced NETs formation via MAPK signaling. (PubMed, Mol Immunol) - "Pharmacological inhibition of each MAPK component (SB203580, U0126, SP600125) phenocopied the effect of CXCL3 knockdown, confirming that CXCL3 acts upstream of MAPK signaling to promote NETs formation. Collectively, this study identifies CXCL3 as a critical regulator of CS-induced NETosis and COPD progression through activation of the MAPK pathway, and highlights epithelial-derived CXCL3 as a promising therapeutic target for COPD intervention."

Journal • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases • CXCL3

Selective JNK3 Inhibition Ameliorates TGF-β-Mediated Glomerular Injury and Fibrosis in the Kidneys. (PubMed, J Am Soc Nephrol) - "These findings suggest that selective JNK3 inhibition effectively attenuates TGF-β-driven glomerular fibrosis and proteinuria without serious complications."

Journal • Chronic Kidney Disease • Fibrosis • Glomerulonephritis • Immunology • Nephrology • Renal Disease • MAPK8 • TGFB1

Identification of two MAPK transcripts in the colonial ascidian Botryllus schlosseri: involvement in immune and stress responses and potential roles in colony growth. (PubMed, Fish Shellfish Immunol) - "Since phagocytic activity is essential for the cyclical renewal of the colony throughout the blastogenetic cycle, we also investigated the effects of colony exposure to MAPK inhibitors, PD98059 and SP600125, targeting the ERK and JNK signalling pathways, respectively. The inhibition of MAPK activity altered colony development and modulated the expression of genes associated with oxidative stress protection (sod, gpx-5) and stress granule dynamics (tiar, ttp), processes involved in post-transcriptional regulation. These findings suggest that MAPK signalling is indispensable for the proper progression of the blastogenetic cycle in B. schlosseri, integrating oxidative stress defence and post-transcriptional control to maintain colony homeostasis."

Journal

The BmCPV-derived viral small peptide vsp1S4(-) suppresses viral replication by triggering apoptosis via the ROS-JNK signalling pathway. (PubMed, Cell Mol Life Sci) - "Pharmacologic interruption of either ROS with N-acetylcysteine (NAC) or JNK signalling with SP600125, a dominant-negative JNK effectively rescues VP7 expression and restores viral replication, confirming that vsp1S4(-)-elicited signalling shows antiviral activity. Thus, BmCPV autonomously limits its own propagation through an antisense-encoded peptide that weaponizes host mitochondrial ROS and JNK, representing a paradigm of programmed self-attenuation operating via antisense translation."

Journal • CASP3 • MAPK8

Chlamydia psittaci induces GSDME-mediated pyroptosis via the ROS-JNK signaling pathway. (PubMed, Mol Cell Biochem) - "Treatment with either the ROS scavenger NAC or the JNK inhibitor SP600125 significantly suppressed pyroptosis...Taken together, our findings suggest that the ROS/JNK signaling pathway modulates GSDME-mediated pyroptosis and concurrently restricts C. psittaci replication in host cells, identifying the ROS-JNK-GSDME axis as a key mechanism in C. psittaci-induced pyroptosis. These findings reveal novel therapeutic targets for the treatment of psittacosis."

Journal • Infectious Disease • Pneumonia • Respiratory Diseases • CASP3 • GSDME • MAPK8

Ketamine enhances histone H3 (Ser10) phosphorylation via JNK signaling and multi-omics profiling of the hippocampus in a psychotic-like mouse model. (PubMed, Behav Brain Funct) - "Critically, pharmacological inhibition of JNK with SP600125 not only reversed this epigenetic mark but also robustly attenuated ketamine-induced hyperlocomotion and cognitive deficits in mice. Our findings suggest that JNK-mediated H3S10 phosphorylation may play a critical role in linking ketamine exposure to psychosis-like phenotypes, providing a mechanistic framework that connects stress-sensitive signaling to rapid chromatin remodeling and sustained transcriptional reprogramming. This work unveils potential novel therapeutic targets for psychosis centered on the JNK-H3S10 phosphorylation axis."

Journal • Preclinical • Anesthesia • CNS Disorders • Cognitive Disorders • Psychiatry

Polyinosinic:polycytidylic acid causes epithelial-mesenchymal transition via BAFF expression in Beas-2B human bronchial epithelial cells. (PubMed, Int J Med Sci) - "Phosphorylation of c-Jun N-terminal kinase (JNK) was enhanced by Poly (I:C) and inhibited by SP600125, JNK inhibitor, leading to a decreased expression of BAFF and aforementioned EMT markers...Pre-treatment with N-acetylcysteine (NAC), ROS scavenger, inhibited Nrf2 activation and JNK phosphorylation...Treatment with recombinant BAFF protein also increased cell migration and EMT marker expression. Taken together, our results demonstrate that Poly (I:C) promotes a regenerative migration of bronchial epithelial cells by inducing BAFF expression through the ROS-dependent JNK-Nrf2 signaling axis."

IO biomarker • Journal • Infectious Disease • CAT • CDH2 • HMOX1 • MAPK8 • SNAI2 • VIM

Aconitine Induces Myocardial Damage in Rats Associated With Activation of the JNK1/2 Signaling Pathway. (PubMed, J Vis Exp) - "Further studies demonstrated that treatment with the JNK inhibitor SP600125 partially reversed Acon-induced myocardial injury in rats. These results indicate that JNK1/2 phosphorylation is involved in the development of myocardial injury induced by acute Aconitine poisoning. The findings suggest that activation of the JNK1/2 signaling pathway contributes to Aconitine-induced myocardial damage, and that inhibition of the JNK1/2 pathway may alleviate myocardial injury caused by acute Aconitine intoxication."

Journal • Preclinical • Cardiovascular • MAPK8

RTA-408 induces JNK-dependent apoptosis and autophagy in breast cancer cells. (PubMed, Oncol Lett) - "Cell viability was quantified using a tetrazolium-based colorimetric assay and apoptosis was evaluated by the Muse® Annexin V & Dead Cell assay based on Annexin V and 7-amino-actinomycin D staining; the expression levels of JNK, p38, ERK, beclin-1, microtubule-associated protein 1 light chain 3B (LC3B), p62/sequestosome 1 (SQSTM1) and poly (ADP-ribose) polymerase (PARP) were assessed by western blotting. Pharmacological inhibition with SP600125 attenuated JNK phosphorylation, reduced apoptotic responses and diminished autophagy-associated marker accumulation, supporting the notion that JNK signaling contributes, at least in part, to these effects. These findings indicate that RTA-408 exerts nanomolar antiproliferative activity in both hormone receptor-positive and triple-negative BC cells through a JNK-dependent mechanism that simultaneously engages apoptosis and autophagy, supporting further in vivo and translational investigation."

Journal • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ANXA5 • BECN1 • ER • MAP1LC3B • SQSTM1

Compensatory Receptor Tyrosine Kinase Signaling Reactivates the RAF–MEK–ERK pathway causing resistance to MEK-inhibition in Glioblastoma. (EACR 2026) - "Treatment efficacy was assessed in 2D using Alamar Blue and crystal violet assays, and in 3D spheroid models, with Bliss scores calculated to determine drug synergy.Result and MEK inhibition with trametinib or selumetinib induced adaptive kinase network remodeling across all GB models, characterized by MEK–AKT crosstalk and enhanced JNK/c-JUN activity...Interestingly, ERK blockade with ulixertinib produced a comparable compensatory response. Combining MEK with JNK inhibition (SP600125) to block parallel activated JNK signaling synergistically reduced cell viability, but did not prevent MEK inhibitor induced MEKSer221 hyperphosphorylation. This study outlines a mechanistic strategy for selecting SMIs to overcome MEK-inhibitor resistance in pdGB models."

Brain Cancer • Glioblastoma • Solid Tumor

Cucurbitacin B Promotes Tumor Necrosis Factor Receptor 1 Ectodomain Shedding by Selectively Activating the Extracellular Signal-Regulated Kinase Signaling Pathway. (PubMed, Int J Mol Sci) - "Cucurbitacin B-induced TNF-R1 shedding was attenuated by TNF-α protease inhibitor 2 and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor U0126, but not by the p38 MAPK inhibitor SB203580 or the c-Jun N-terminal kinase (JNK) inhibitor SP600125. Consistent with these results, cucurbitacin B promoted the rapid phosphorylation of rapidly accelerated fibrosarcoma 1 (RAF1) and ERK, but exerted minimal effects on the phosphorylation of p38 MAPK and JNK. Collectively, these results demonstrate that cucurbitacin B selectively activated the RAF1-MEK-ERK pathway, which was essential for TNF-R1 ectodomain shedding."

Journal • Fibrosarcoma • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • MAPK8 • TNFA • TNFRSF1A

Mechanism Study on How PTX3 Drives EMT and Fibrosis of Renal Tubular Epithelial Cells in Diabetic Kidney Disease by Activating the JNK Pathway. (PubMed, Curr Med Chem) - "PTX3 promotes renal tubular EMT and fibrosis by activating the JNK signaling pathway. Targeting the PTX3-JNK axis may provide a novel therapeutic strategy for DKD."

Journal • Diabetes • Diabetic Nephropathy • Fibrosis • Immunology • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • CDH1 • CDH2 • ICAM1 • IL6 • MAPK8 • PTX3 • TGFB1 • TNFA • VIM

Targeting CD30L Alleviates Airway Remodeling via JNK/p38 MAPK Pathway in OVA-Induced Asthmatic Mice. (PubMed, Allergy Asthma Immunol Res) - "Collectively, these findings demonstrate that CD30L critically regulates asthma airway remodeling via the JNK/p38 MAPK pathway, strongly suggesting its therapeutic potential as a target for airway remodeling in asthma."

Journal • Preclinical • Asthma • Immunology • Oncology • Pulmonary Disease • Respiratory Diseases • MAPK8 • TNFA • TNFRSF8 • TNFSF8

JNK inhibitor SP600125 alleviates TGF-β2-induced epithelial-mesenchymal transition in RPE cell via TGF-βR2/Smad2/3 and JNK/c-Jun pathway. (PubMed, Int J Ophthalmol) - "JNK inhibitor SP600125 suppresses TGF-β2-induced the increases in cell viability, migration, proliferation, and EMT in RPE cells via the TGF-βR2/Smad2/3 and JNK/c-Jun signaling pathways."

Journal • CDH2 • MAPK8 • SMAD2 • TGFB1 • TGFB2 • TGFBR2 • VIM

Doxorubicin compromises blood-brain barrier integrity by suppressing annexin A1 expression. (PubMed, Open Life Sci) - "In vitro, cells were treated with 1 μM DOX for 48 h, with or without pretreatment with 50 μM AP-1 inhibitor (SR11302) or 50 nM miR-196a inhibitor (LNA-antimiR-196a) for 24 h; in vivo, mice received weekly intraperitoneal injections of 4 mg/kg DOX for 5 weeks, with or without 1 h pretreatment with 10 mg/kg AP-1 inhibitor (SP600125) or 5 mg/kg LNA-antimiR-196a. Inhibition of AP-1 or miR-196a reversed these DOX-induced abnormalities. Collectively, our findings demonstrate that DOX compromises BBB integrity by activating the AP-1/miR-196a axis, which suppresses ANXA1 and ultimately disrupts tight junctions - providing a novel mechanistic basis for DOX-induced neurotoxicity."

Journal • ANXA1 • CLDN5 • OCLN • TJP1