SP600125 / BMS - LARVOL DELTA

Crosstalk between oncogenic signaling pathways as driver of therapy resistance against small molecule inhibitors in Glioblastoma (EACR 2025) - "Result and SMIs targeting downstream effector kinases (Trametinib, Buparlisib, Abemaciclib; IC50 70nM-1µM) or membrane-bound tyrosine kinase receptors (Afatinib, Capmatinib, Axitinib; IC50 1-15µM) reduced cell viability...Combined trametinib and SP600125 (JNKi) mitigated JNK/c-Jun activation and synergistically reduced cell viability (Bliss >20), but failed to suppress MEKSer221 hyperphosphorylation... Trametinib reduces cell viability but triggers compensatory signaling, including MEKSer221 hyperphosphorylation. This study presents a mechanistically driven selection of tumor-tailored combination treatments to overcome resistance to SMI monotherapy in pdGBM models, highlighting VEGFR co-inhibition as a promising combinatorial strategy with trametinib."

Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Nonthermal plasma jet mitigates viral replication and inflammation in human coronavirus 229E-infected lung cells by targeting the NF-κB and MAPK pathways. (PubMed, Microb Pathog) - "The pretreatment of the virus with SP600125 inhibitor and NTPJ resulted in a significant reduction in the expression ratio of viral genes ACE-2, S gene and RdRP/Helicase. Therefore, these results suggest that NTPJ enhances both anti-viral and anti-inflammatory responses, making it a promising candidate for prevention and treatment of corona virus infections."

Journal • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • COLEC10 • IFNG • IL1B • IL6 • TNFA

Role of Central Inflammatory and Oxidative Pathways in the Morphine Exacerbation of Cardiovascular Effects of Sepsis in Rats. (PubMed, Pharmaceuticals (Basel)) - "The morphine effects were mostly eliminated following (i) blockade of μ-opioid receptors by i.v. naloxone and (ii) inhibition of central PI3K, MAPK-ERK, MAPK-JNK, NADPH oxidase (NADPHox), or Rho-kinase (ROCK) by i.c. wortmannin, PD98059, SP600125, diphenyleneiodonium, and fasudil, respectively. Morphine worsens cardiovascular and autonomic disturbances caused by sepsis through a mechanism mediated via μ-opioid receptors and upregulated central inflammatory, chemotactic, and oxidative signals. Clinical studies are warranted to re-affirm the adverse cardiovascular interaction between opioids and the septic challenge."

IO biomarker • Journal • Preclinical • Addiction (Opioid and Alcohol) • Cardiovascular • Critical care • Hypotension • Infectious Disease • Inflammation • Pain • Septic Shock • CCL2 • TLR4

Targeting Decidual Macrophage Polarization through JNK Signaling Pathway Inhibition Alleviates Adverse Pregnancy Outcomes in Early Spontaneous Abortion. (PubMed, Reprod Sci) - "To enhance our knowledge of macrophage polarization, activation of M1 macrophages was achieved using LPS and IFN-γ, while activation of M2 macrophages was accomplished using IL-4 and IL-13, followed by treatment with varying concentrations of the JNK inhibitor (SP600125) to see how it affected the balance between the two macrophage types...Furthermore, blocking the JNK signaling pathway significantly increased the M2 phenotype of DMs and reduced the resorption rate of mouse embryos. The current study elucidated that blocking the JNK signaling pathway suppressed the pro-inflammatory polarization in macrophages, thereby attenuating the adverse pregnancy outcomes of ESA."

Adverse events • Journal • Immunology • IFNG • IL10 • IL13 • IL4 • IL6 • MAPK8 • TGFB1 • TNFA

Cynaropicrin induces the apoptosis of colorectal cancer cells by elevating reactive oxygen species and activating the JNK/p38 MAPK. (PubMed, Am J Cancer Res) - "This study was performed to investigate the anticancer activity of cynaropicrin (a natural product) in CRC HCT116 cells and an oxaliplatin (Ox)-resistant HCT116 strain (HCT116-OxR)...In addition, treatment with the kinase-specific inhibitors SP600125 and SB203580 confirmed that this apoptosis was mediated by JNK and p38 MAPK. Flow cytometry analysis using the CellROX™ kit showed cynaropicrin increased reactive oxygen species (ROS) levels, and N-acetylcysteine pretreatment confirmed ROS mediated the cytotoxicity of cynaropicrin...In conclusion, cynaropicrin demonstrated anticancer activity against CRC cells by elevating ROS levels, activating JNK and p38 MAPK, and inducing cell cycle arrest leading to apoptosis. Further studies are warranted to evaluate the therapeutic potential of cynaropicrin in CRC."

Journal • Colorectal Cancer • Oncology • Solid Tumor • ANXA5 • BCL2

IFN-Γ DAMAGES SALIVARY GLAND EPITHELIAL CELLS BY ACTIVATING THE IRE1–JNK–AP-1 SIGNALING AXIS IN SJÖGREN'S SYNDROME (EULAR 2025) - "Various inhibitors—TUDCA (an ERS inhibitor), SP600125 (a JNK inhibitor), and SR11302 (an AP-1 inhibitor)—were added to evaluate whether ERS-related proteins (GRP78, CHOP) and p-JNK, p-cFos, p-cJun phosphorylation levels decrease, and to measure changes in MMP9 secretion in the cell culture supernatants. Our study provides a systematic elucidation of the potential mechanism by which IFN-γ activates the IRE1–JNK–AP-1 signaling axis to induce salivary gland epithelial cell damage. Clinical samples and single-cell sequencing data collectively reveal significant upregulation of ERS and the IFN-γ pathway in SS patients. In vitro experiments further confirm that IFN-γ stimulation increases ERS levels and activates the IRE1–JNK–AP-1 signaling axis, thereby elevating MMP9 secretion and exacerbating cellular injury."

Immunology • Inflammation • Sjogren's Syndrome • ATF6 • ERN1 • FOS • HSPA5 • IFNG • MMP9

The influence of PPARγ mediated MAPK and NF-κB activation in AGEs stimulated apoptosis and autophagy in human chondrocytes. (PubMed, J Orthop) - "Compared to AGEs alone, pioglitazone, specific MAPK inhibitors (SP600125 and SB203580, but not PD98059), and NF-κB inhibitors reduced MMP-13 and TNF-α expression. These results suggest that PPARγ agonism could serve as a dual-target therapeutic approach for OA, with pioglitazone emerging as a potential disease-modifying agent. Further clinical research is needed to confirm its therapeutic benefits in OA management."

Journal • Immunology • Metabolic Disorders • Osteoarthritis • Pain • Rheumatology • ANXA5 • CASP3 • MMP13 • NFKBIA • PPARG • TNFA

GRPEL2 Modulates Apoptosis in Esophageal Squamous Cell Carcinoma via the JNK Signaling Pathway. (PubMed, Mol Carcinog) - "Additionally, the apoptosis induced by GRPEL2 loss can be largely reversed by treatment with SP600125, a JNK inhibitor. We identified Vandetanib, a known antitumor agent, as a promising molecule that not only exhibits robust binding activity but also effectively reduces GRPEL2 protein levels. In conclusion, the data presented herein implicate GRPEL2 as a pivotal regulator in ESCC, modulating the MAPK/JNK signaling cascade to potentiate apoptosis, thereby offering a specific therapeutic vulnerability for targeting ESCC."

Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Metabolic Disorders • Oncology • Squamous Cell Carcinoma

Apatinib modulates sorafenib-resistant hepatocellular carcinoma through inhibiting the EGFR/JNK/ERK signaling pathway. (PubMed, Oncol Res) - "Notably, SP600125 and PD98059 contributed to the inhibition of EMT and EGFR/JNK/ERK pathway-related proteins by apatinib in sorafenib-resistant HCC. Apatinib potentially hindered the progression of sorafenib-resistant HCC by suppressing both EMT and the EGFR/JNK/ERK pathway."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • MAPK8

Exercise Training Promotes Neural Remodeling and Vascular Regeneration in Cerebral Ischemic Rats Through the JNK/c-jun Signaling Pathway. (PubMed, Mol Neurobiol) - "However, the protective benefits of exercise training were offset by the JNK inhibitor, SP600125. After cerebral ischemia, exercise training can promote neural structural remodeling, neurological functional recovery, and vascular regeneration. These processes may be achieved by activating the JNK/c-jun signaling pathway."

Journal • Preclinical • Cardiovascular • Reperfusion Injury

Enhancement of ASIC currents by angiotensin II in rat dorsal root ganglion neurons. (PubMed, Neuropharmacology) - "The enhancing effect of Ang II on ASIC currents was prevented by either the PKC inhibitor GF109203x, or the ERK inhibitor U0126, but not by the p38 inhibitor SB202190 or the JNK inhibitor SP600125. These results indicated that Ang II enhanced the functional activity of ASICs through a mechanism that depended on AT1R, the intracellular PKC, and the ERK signaling pathway. Our findings provided evidence that Ang II is a promising target for developing new treatments for pain, at least for pain associated with tissue acidification."

Journal • Preclinical • Pain

The Effect of D-Allulose on Lipid Accumulation in HepG2 Hepatoblastoma Cells (ENDO 2025) - "Other MAP kinase inhibitors, including SB203580, SP600125, and BIX10289 had no effect on reporter gene expression. Oleic acid treatment, but not D-allulose or gemfibrozil, decreased sterol response element binding protein 1 and sterol response element binding protein 2 expression relative to cells not exposed to oleic acid, while peroxisome proliferator-activated receptor γ expression did not change. These results indicate that D-allulose mimics gemfibrozil effects on lipid content in HepG2 cells by promoting fatty acid β-oxidation via PPARα."

Addiction (Opioid and Alcohol) • Hepatoblastoma • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Oncology • Solid Tumor • CPT1A • PPARA

Sinomenine Ameliorates Liver Fibrosis by Blocking TGF-β/SMAD and c-JUN Signaling. (PubMed, Phytother Res) - "Pretreatment with TP0427736 (a SMAD2/3 inhibitor) or SP600125 (a c-JUN inhibitor) synergistically enhanced SIN-mediated α-SMA suppression in HSC-T6 cells. SIN ameliorates liver fibrosis through inhibition of TGF-β/SMAD and c-JUN signaling pathways. These findings position SIN as a promising therapeutic candidate for liver fibrotic disorders."

Journal • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • JUN • MMP2 • TGFB1

Suppression of NOX2-Derived Reactive Oxygen Species (ROS) Reduces Epithelial-to-MesEnchymal Transition Through Blocking SiO2-Regulated JNK Activation. (PubMed, Toxics) - "Further mechanistic analyses demonstrated that JNK signaling amplifies NOX2 expression and ROS production induced by silica exposure, while treatment with the JNK inhibitor SP600125 mitigates these effects...These results suggest a positive feedback loop between JNK and NOX2 signaling, which may drive EMT in lung epithelial cells following silica exposure. (4) This reciprocal interaction appears to play a critical role in lung epithelial cell damage and the pathogenesis of silicosis, shedding light on the molecular mechanisms underlying profibrogenic disease and offering potential avenues for therapeutic intervention."

Journal • Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • MAPK8

RETRACTION: Leptin Induces Matrix Metalloproteinase 7 Expression to Promote Ovarian Cancer Cell Invasion by Activating ERK and JNK Pathways. (PubMed, J Cell Biochem) - "Specifically, overlapping areas between the panels showing the "Lep+SP600125" and "Lep+PD098059" groups in SKOV3 cells have been detected within Figure 4...As a result, the article is retracted. The authors have been informed of the retraction decision and disagree with it."

Journal • Oncology • Ovarian Cancer • Solid Tumor • GAPDH • LEP • MMP7

Downstream Signaling Mediators of CXCL6-driven Synthesis of Collagen in Human Fibroblasts (ATS 2025) - "Doxycycline was used to induce CXCL6 expression and secretion in BJ13 cells. A panel of specific pathway inhibitors were added to cells, including SR11302 (AP1), MK2206 (AKT), SB203850 (p38), SP600125 (JNK), PD184352 (MEK), FASUDIL (ROCK/RHO), SLV2436 (MNK1/2), Omipalisib (mTOR/PI3K), Torin (mTOR), and Reparixin (CXCR1/2)... We identified that CXCL6 induces collagen production through multiple pathways including mTOR, p38, JNK and MEK. Targeting a combination of these pathways may be a potential therapeutic direction for IPF treatment."

Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • CXCL6 • CXCR1 • SMAD3 • TGFB1

Role of JNK Activation in Delaying Autophagy Completion After E-cigarette Vape Exposure (ATS 2025) - " Cultured small airway epithelial cells (hSAEC1-KT) were treated with a broad JNK inhibitor (SP600125, 50 mM, 1h; Selleckchem) prior to EV exposure (Juul, Virgina Tobacco, 5 mg/mL nicotine; 7.5 mM; 2, 4, or 24 hours)... Following inhibition of mTOR activity, EV triggered autophagy with progressive accumulation of p62/SQTM1, denoting incomplete fusion/digestion of autophagosomes. JNK activation by EV contributes to impaired autophagy completion, by yet unknown mechanisms. JNK inhibition may ameliorate lung injury repair following EV exposure, prompting further studies into which specific JNK isoform is involved in this process."

Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pneumonia • Respiratory Diseases • MAP1A • SQSTM1

Midkine Promote Atherosclerosis by Regulating the Expression of ATP-Binding Cassette Transporter A1 via Activator Protein-1. (PubMed, Cardiovasc Drugs Ther) - "Our findings unveil a novel mechanistic pathway in atherosclerosis, whereby MK promotes the development of atherosclerosis by up-regulating AP-1 in macrophages via the PI3K/AKT/JNK signaling cascade."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • ABCA1 • APOE • FOS

Pretreatment of cancer cells with inhibitors of PKCδ, EGFR, and JNK increased intracellular hypericin content and enhanced the effectiveness of photodynamic therapy. (PubMed, J Photochem Photobiol B) - "We assessed the effects of inhibitors of epidermal growth factor receptor (EGFR) (Tyr - tyrphostin AG 1478) and c-Jun N-terminal kinase (JNK) (SP - SP600125, Lico - licochalcone A), as well as protein kinase C (PKC) activator (TPA) and inhibitor (Rot - rottlerin). More importantly, the sensitizing effects of the inhibitors were linked to increased intracellular HY accumulation, indicating reduced BCRP efflux activity. While the exact mechanisms behind these effects require further investigation, our findings suggest that targeting BCRP and associated signaling pathways could enhance PDT outcomes in cancer treatment."

Journal • Breast Cancer • Oncology • Solid Tumor • EGFR • MAPK8

Mesenchymal stem cells protect the integrity of the alveolar epithelial barrier through extracellular vesicles by inhibiting MAPK-mediated necroptosis. (PubMed, Stem Cell Res Ther) - "Our results suggest that human menstrual blood-derived endometrial stem cells mitigate lung injury and improve alveolar barrier properties by inhibiting MAPK-mediated necroptosis through extracellular vesicles, supporting the application of MenSCs or MenSC-derived extracellular vesicles to treat ALI or ARDS."

Journal • Acute Lung Injury • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases

Gossypin induces apoptosis and autophagy via the MAPK/JNK pathway in HT‑29 human colorectal cancer cells. (PubMed, Int J Mol Med) - "To investigate autophagy during cell death, the effects of the early autophagy inhibitor 3‑methyladenine (3‑MA) and the late autophagy inhibitor hydroxychloroquine on cell viability and the expression of apoptosis‑related proteins were assessed...The JNK inhibitor SP600125 was used to confirm the role of the JNK pathway in gossypin‑induced apoptosis and autophagy...Finally, TUNEL and immunohistochemistry experiments confirmed the induction of apoptosis and p‑JNK upregulation in these tumors in vivo. In conclusion, the present study suggested that gossypin may induce MAPK/JNK‑mediated apoptosis and autophagy in HT‑29 CRC cells, highlighting the potential of gossypin as an anticancer agent."

Journal • Colorectal Cancer • Oncology • Solid Tumor • BCL2

Lipocalin-2-mediated ferroptosis as a target for protection against light-induced photoreceptor degeneration. (PubMed, Mol Med) - "LCN2 is a key regulator of light-induced ferroptosis in photoreceptors by modulating the JNK pathway. Therefore, LCN2 presents a new target for the treatment of retinal degeneration."

Journal • Ophthalmology • GPX4 • LCN2 • MAPK8 • SLC7A11

Antimony induces mitochondria-dependent and ER stress-triggered apoptosis via the oxidative stress-activated JNK signaling pathway in pancreatic islet β-cells. (PubMed, Toxicology) - "Pretreatment with SP600125 (an inhibitor of JNK) and antioxidant NAC, but not PD98059 (an inhibitor of ERK) or compound C (an inhibitor of AMPK), effectively abrogated the cytotoxicity, ER stress responses, mitochondrial dysfunction, apoptotic events, insulin secretion inhibition, and JNK activation in Sb-exposed rat pancreatic islet β-cells. However, SP600125 did not prevent ROS generation, which was inhibited by the antioxidant NAC. Collectively, the results demonstrate exposure to Sb to exert β-cell cytotoxicity through oxidative stress-activated JNK signaling downstream-regulated mitochondria-dependent and ER stress-triggered cell apoptotic pathways, eventually resulting in the death of rat pancreatic islet β-cells."

Journal • Diabetes • Metabolic Disorders • CASP12 • CASP3 • CASP7 • CASP9 • PARP1

Impact of Escherichia coli and Lipopolysaccharide on the MAPK Signaling Pathway, MMPs, TIMPs, and the uPA System in Bovine Mammary Epithelial Cells. (PubMed, Int J Mol Sci) - "BMECs were exposed to MAPK inhibitors (the JNK inhibitor SP600125, the ERK inhibitor PD98059, and the P38 inhibitor SB203580) after treatments with heat-inactivated E. coli (106 CFU/mL), LPS (7.5 µg/mL), or a combination of the two for 6, 12, 24, and 48 h. The mRNA and protein levels of MMP-1, MMP-2, MMP-3, MMP-9, MMP-13, TIMP-1, TIMP-2, uPA, uPAR, and PAI-1 were assessed using RT-qPCR and Western blot analysis. In conclusion, heat-inactivated E. coli and LPS can activate the MAPK signaling pathway in BMECs. Inhibiting this signaling pathway can modulate the expression of TIMP-1, TIMP -2, and PAI-1 at both mRNA and protein levels."

Journal • Infectious Disease • MMP1 • MMP13 • MMP2 • MMP3 • MMP9 • TIMP1 • TIMP2

Effects of Arsenic-induced Diabetic Vascular Diseases through Mitogen-activated Protein Kinase Signaling Pathway: In vitro and In vivo Studies. (PubMed, J Physiol Investig) - "However, in glucose + As group, treatment with SP600125 and U10126 treatment decreased ROS production by 80.5% and 84%, respectively, and restored MMP and cell viability. The glucose-regulated protein 78 level increased in the As as well as glucose + As groups. Our findings demonstrate that As exacerbates vascular damage in individuals with diabetes and its associated complications through the activation of the mitogen-activated protein kinase signaling pathway."

Journal • Preclinical • Cardiovascular • Diabetes • Metabolic Disorders • Peripheral Arterial Disease