PD98059 / Wayne State University - LARVOL DELTA

Construction of a Prognostic Model Based on Insulin Resistance-Related Genes to Predict TACE Response and Identification of PD-98059 as a Potential Therapeutic Agent. (PubMed, J Hepatocell Carcinoma) - "Cell experiments confirmed that PD-98059 synergistically enhanced the inhibitory effect of lobaplatin on HCC cell proliferation. The insulin resistance model tailored for TACE effectively predicts patient prognosis. Via the effect of MEK inhibitor PD-98059, the efficacy of TACE in patients can be improved."

Journal • Diabetes • Hepatocellular Cancer • Liver Cancer • Metabolic Disorders • Oncology • Solid Tumor • DUSP9 • SERPINE1

1β,6α-Dihydroxyeudesm-4(15)-ene Protects Against MPP+-Induced Cytotoxicity in SH-SY5Y Cells: An In Vitro Model of Parkinson's Disease. (PubMed, J Med Food) - "Furthermore, treatment with the ERK inhibitor PD98059 abolished the DE-induced protection against MPP+ cytotoxicity, and p38 inhibitor SB203580 or JNK inhibitor SP600125 mimicked DE-induced cytoprotective effects against MPP+. Our results demonstrate that DE exerts neuroprotective effects against MPP+-induced cytotoxicity by mitigating nitrosative stress, alleviating mitochondrial dysfunction, and modulating the mitogen-activated protein kinase signaling pathway, suggesting its therapeutic potential in PD."

Journal • Preclinical • CNS Disorders • Metabolic Disorders • Movement Disorders • Parkinson's Disease • BAX • BCL2 • CASP3 • MAPK8

Endothelin-1 upregulates cyclooxygenase-2 expression and prostaglandin E2 synthesis in human periodontal ligament cells-an in vitro study. (PubMed, J Orthod Sci) - "ET-1 upregulates COX-2 expression and PGE2 synthesis in hPDL cells through an ERK-independent pathway, while exerting no significant effect on VEGF expression. Further studies are warranted to assess the therapeutic potential of ET-1 in accelerating OTM."

Journal • Preclinical • EDN1 • HPDL • PTGS2

Th17 cell mediated oligodendrocyte precursor cell arrest drives hippocampal demyelination in diabetic cognitive dysfunction. (PubMed, Clin Sci (Lond)) - "Crucially, co-treatment with the ERK inhibitor PD98059 partially reversed the protective effects of IL-17A NAbs on these parameters. These findings indicate that IL-17A, secreted by infiltrating Th17 cells, exacerbates hippocampal demyelination in DCD by inhibiting oligodendrocyte precursor cell (OPC) maturation via suppression of the ERK1/2 pathway and concurrently activating microglia to amplify neuroinflammation, ultimately driving cognitive impairment."

Journal • Alzheimer's Disease • Cognitive Disorders • Diabetes • Inflammation • Metabolic Disorders • Solid Tumor • CD4 • IL10 • IL17A • IL1B • IL4 • IL6 • OLIG2 • TJP1 • TNFA

Exposure to 2-chlorohydroquinone induces systemic vascular disorders and increases the risk of cerebral hemorrhage in zebrafish larvae. (PubMed, J Hazard Mater) - "Network pharmacology and molecular docking identified MAPK/ERK pathway as a core pathway, and pharmacological inhibition of the MAPK/ERK pathway with PD98059 ameliorated vascular defects and hemorrhage. These findings reveal that 2-CHQ impairs vascular integrity via MAPK/ERK activation, providing critical insights into its mechanistic toxicity and potential environmental health risks."

Journal • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders • Inflammation • KDR • PDGFRB

The Locus Coeruleus Modulates Acute Itch via ERK-Dependent Neuronal Excitability. (PubMed, Eur J Pharmacol) - "In this study, we established acute itch models by intradermal injection of Compound 48/80 (C48/80) and chloroquine (CQ) into the neck region of mice...Microinjection of the ERK pathway inhibitor PD98059 into the LC reduced pERK levels and significantly attenuated scratching behaviors induced by both C48/80 and CQ...Under step-current stimulation, these neurons showed elevated rheobase and reduced spiking. These results establish a causal role of the ERK pathway in the LC in the regulation of neuronal excitability and acute itch, providing a mechanistic foundation for future therapeutic exploration."

Journal • FOS

Bioinformatics analysis unveils hub genes in the pathogenesis of sevoflurane anesthesia-induced respiratory depression. (PubMed, Comput Methods Biomech Biomed Engin) - "PD-98059 was predicted as a potential therapeutic candidate and was confirmed to reverse sevoflurane-induced upregulation of ICAM1. Overall, this study identifies key genes and inflammatory pathways associated with sevoflurane-induced respiratory suppression, providing new insights into its molecular mechanisms and potential therapeutic strategies."

Journal • Anesthesia • CNS Disorders • Depression • Inflammation • Mood Disorders • Psychiatry • CCL2 • CXCL1 • CXCL8 • ICAM1 • IL1B • IL6 • MMP9 • VCAM1

Oxygen-dependent regulation of ADAMTS1 by VEGFA defines a novel VEGFA-HIF-ADAMTS1 axis in hepatocellular cancer. (PubMed, Tissue Cell) - "The partial reversal of this effect by the MEK/ERK inhibitor PD98059 confirmed the role of this pathway in the transcriptional control of VEGFA...Integrative bioinformatic analyses of GEO and TCGA-LIHC datasets supported these experimental findings, revealing hypoxia-associated upregulation of VEGFA, positive correlations between hypoxia scores and VEGFA/HIF1A expression, and context-dependent associations between ADAMTS1 expression, hypoxia signaling, and angiogenesis-related gene networks. These results identify ADAMTS1 as a hypoxia-responsive gene regulated through VEGFA-driven convergence of MAPK and PI3K/AKT signaling on a transcriptionally complex promoter, providing mechanistic insight into hypoxia-associated extracellular matrix remodeling in cancer."

Journal • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • ADAMTS1 • ATF1 • HIF1A • JUN

Mechanistic Study on Catechin-Derived Carbon Quantum Dots Promoting Wound Healing via Activating the MAPK/ERK-p38 Signaling Pathway. (PubMed, Mol Pharm) - "Innovatively, we used specific inhibitors (PD98059 and SB203580) to verify the mechanism both in vitro and in animal models, confirming that once the ERK/p38 pathway is blocked, the wound-healing-promoting effect of Ct-CQDs is significantly inhibited. In conclusion, this study provides a theoretical basis for the development of novel nano wound dressings based on natural products and offers solid theoretical and experimental support for their application as a nanodrug therapeutic strategy with clear mechanisms, high efficiency, and safety."

Journal

Formononetin attenuates corticosterone-induced depressive-like behaviors and neuronal damage via ERα/ERK-CREB-BDNF signaling pathway. (PubMed, J Pharm Pharmacol) - "FMN exerts antidepressant effects via ERα-mediated neurotrophic signaling (ERK-CREB-BDNF), offering a mechanistic foundation for natural antidepressant development."

Journal • CNS Disorders • Depression • Psychiatry

TMEM121 suppresses cervical cancer cell proliferation and migration via interaction with the ERK pathway. (PubMed, Am J Cancer Res) - "Additionally, flow cytometry analysis showed that the ERK inhibitor PD98059 reversed the S phase cell cycle arrest induced by TMEM121 overexpression. Collectively, these findings suggest that TMEM121 exerts its inhibitory effects on the growth, proliferation, and invasion of cervical cancer cells through its interaction with ERK, providing a theoretical basis for the development of novel diagnostic and therapeutic strategies for cervical cancer."

Journal • Cervical Cancer • Oncology • Solid Tumor • MAPK1

Apelin-13 induces lordosis behavior in estradiol-primed ovariectomized rats via the activation of multiple protein kinases in the ventromedial hypothalamus. (PubMed, Physiol Behav) - "However, PD98059 significantly reduced both the LQ and LS at 120 and 240 min. These data indicate that apelin-13 exerts its facilitatory effects on lordosis through MAPK, PKC, and/or Src, but not PKA pathways."

Journal • Preclinical • Endocrine Cancer

Synergistic Neuroprotection of Combined Shenmai and Hypothermia in Cerebral Ischemia-Reperfusion Injury via ERK-Dependent Anti-inflammatory Effects. (PubMed, Mol Neurobiol) - "The ERK inhibitor PD98059 verified mechanistic contributions...Intracarotid Shenmai with hypothermia synergistically attenuates cerebral I/R injury through ERK-mediated anti-inflammatory effects, including reduced microglial activation markers. These findings provide mechanistic preclinical evidence supporting Shenmai as an effective pharmacological adjunct to intraarterial hypothermia and suggest a promising therapeutic approach for mitigating reperfusion injury following EVT in acute ischemic stroke."

Journal • Cardiovascular • Inflammation • Ischemic stroke • Reperfusion Injury

Neuronal pentraxin 2 in peripheral sensory neurons drives chronic itch through potentiation of the interleukin-31/interleukin-31 receptor pathway in atopic dermatitis. (PubMed, Int Immunopharmacol) - "Additionally, PD98059 also significantly reduced the upregulation and release of NPTX2 caused by IL-31 stimulation. Our results offer a new understanding of the molecular mechanisms underlying chronic pruritus in the MC903-induced AD model, highlighting NPTX2-dependent signaling as a key therapeutic strategy for refractory itch disorders."

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Pruritus

Tumor-Macrophage-Nerve interactions drive neuroinflammation and neuropathic pain in prostate cancer perineural invasion. (PubMed, Brain Behav Immun) - "This model provides insight into neuroinflammatory tumor-macrophage-nerve interactions associated with neuronal hyperexcitability. Although focused in scope, it enables stepwise investigation of tumor-induced neuronal responses and offers a useful platform for evaluating neuroinflammatory mechanisms of tumor invasion and for identifying potential therapeutic targets."

Journal • Genito-urinary Cancer • Neuralgia • Oncology • Pain • Pancreatic Cancer • Prostate Cancer • Solid Tumor • IL1B • IL1R1 • TIMP1 • TNFA

Effect of exercise preconditioning on myocardial content of Sphingosine1-phosphate and its mechanism in rats after exhaustive exercise. (PubMed, PLoS One) - "In summary, beyond confirming S1P elevation with exercise preconditioning, our findings propose the S1P→MAPK signaling axis as a novel mechanistic pathway warranting future validation."

Journal • Preclinical • S1PR1

Regulation of Renal Transporters by Pro-inflammatory Cytokines in Human Proximal Tubular Epithelial Cells: Identification of the Perpetrator and Mechanisms. (PubMed, bioRxiv) - "To determine mechanisms of these effects, selective MAPK/NF-κB inhibitors (ERK [PD98059], p38 MAPK [SB203580], JNK [SP600125], and NF-κB [PDTC]), individually or as a cocktail, were used. These data provide quantitative inputs for physiologically based pharmacokinetic models to predict how inflammation alters renal transporter-mediated drug clearance, informing dose adjustment and risk assessment for disease-drug and drug-drug interactions in patients with inflammatory kidney disease or systemic infections. They also highlight signaling nodes where anti-inflammatory therapies might inadvertently modify renal drug transport."

Journal • Infectious Disease • Inflammation • Nephrology • Renal Disease • ABCC3 • IFNG • IL10 • IL1B • IL4 • IL6 • SLC22A2 • TNFA

Mechanistic Insights into Anti-Melanogenic Effects of Fisetin: PKCα-Induced β-Catenin Degradation, ERK/MITF Inhibition, and Direct Tyrosinase Suppression. (PubMed, Int J Mol Sci) - "The proteasome inhibitor MG132 confirmed that fisetin accelerates β-catenin and MITF degradation. Additionally, inhibition of the PI3K/AKT pathway by LY294002 or the ERK pathway by PD98059 reversed fisetin's reduction of tyrosinase activity and melanin synthesis, further verifying the participation of these pathways. Computational docking integrated with deep learning-based CNN scoring revealed that fisetin interacts with PKCα, β-catenin, tyrosinase, and TYRP1. Collectively, these findings suggest that fisetin exerts multi-targeted inhibitory effects on melanogenesis, highlighting its potential as a therapeutic and cosmetic agent for hyperpigmentation."

Journal • Dermatology • Dermatopathology • Melanoma • Oncology • Solid Tumor • Targeted Protein Degradation • CTNNB1 • MITF • Tyrosinase • TYRP1

FAM83A acts as an amplifier for lipogenic signaling to facilitate the pathogenesis of metabolic dysfunction-associated steatohepatitis. (PubMed, Metabolism) - "FAM83A promotes MASH pathogenesis by interacting with RAF1 to activate ERK signaling, thereby stimulating fatty acid and cholesterol biosynthesis. Targeting this axis may offer therapeutic potential for MASH and metabolic dyslipidemia."

Journal • Dyslipidemia • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • EGFR • FAM83A

WuFu Decoction alleviates osteoarthritis by regulating TGF-β1/Smad and ERK1/2 pathways. (PubMed, Histol Histopathol) - "Furthermore, TGF-β1 inhibitor (Decorin) reversed the improvement effect of WFD on OA, but ERK1/2 inhibitor (PD98059) promoted this improvement effect...This study also identified active ingredients, such as Fumaric acid, Glycyrrhizic acid, Albiflorin, and Isoliquiritigenin. It provides a basis for the clinical application of WFD and for the promotion and development of TCM."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology • BMP7 • COL2A1 • IL1B • MMP13 • SMAD2 • SMAD3 • TGFB1 • TGFBR2 • TNFA • TRAP

LGALS3 promotes liver fibrosis by enhancing the expression and phosphorylation of ERK1/2. (PubMed, Eur J Med Res) - "In the LGALS3 overexpression cell model, PD98059 intervention was applied to mimic the therapeutic effect on liver fibrosis.​ LGALS3 overexpression significantly promoted the proliferation and migration of LX-2 cells, along with the expression and phosphorylation of ERK1/2...These findings enhance our understanding of the pathological process of liver fibrosis, suggesting that targeting the LGALS3-ERK1/2 axis may represent a promising target for further investigation in liver fibrosis. It also provides potential targets and innovative directions for the development of anti-liver fibrosis drugs."

Journal • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • LGALS3 • MAPK1 • MAPK3 • TGFB1

Acupuncture mitigates sciatic neuropathic pain in lumbar disc herniation via inhibiting spinal CXCL12/CXCR4-driven glial activation and neuroinflammation. (PubMed, J Neuroimmunol) - "Pharmacological blockade of CXCR4 with AMD3100 alleviated hypersensitivity and reduced neuronal and glial activation. Acupuncture also inhibited ERK1/2 and NF-κB phosphorylation, and selective inhibition of these pathways with PD98059 or PDTC reproduced its analgesic effects. These findings identify the CXCL12/CXCR4-ERK/NF-κB axis as a critical mediator of LDH-induced neuroinflammation and demonstrate that acupuncture mitigates neuropathic pain by suppressing this signaling pathway and glial activation."

Journal • Back Pain • CNS Disorders • Immunology • Inflammation • Lumbar Back Pain • Musculoskeletal Diseases • Musculoskeletal Pain • Neuralgia • Pain • CXCL12 • CXCR4 • FOS • GFAP • IL1B • IL6 • TNFA

RRBP1 Inhibition Reduces Microglial M1 Polarization and Inflammation-Mediated Neuronal Loss and Oxidative Stress by Regulating ERK Pathway in Alzheimer's Disease. (PubMed, Mol Neurobiol) - "pERK/ERK was lowered after PD98059 treatment, which attenuated the effect of RRBP1 inhibition on microglial M1/M2 phenotypes and inflammatory cytokines in BV-2 and HMC3 cells, and further weakened the effect of microglial RRBP1 inhibition on cell viability, apoptosis rate, ROS, and SOD in HT-22 and SH-SY5Y cells. RRBP1 inhibition represses microglial M1 polarization and inflammation-mediated neuronal loss and oxidative stress by modifying the ERK pathway in AD."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation • Neuroblastoma • Oncology • Solid Tumor • IL1B • TNFA

YWHAH‑driven autophagy via MAPK/ERK signaling enhances CRC cell migration and invasion. (PubMed, Int J Mol Med) - "The ERK inhibitor PD98059 reversed autophagy activation by YWHAH knockdown, while the ERK agonist U‑46619 reversed autophagy suppression by YWHAH overexpression. Additionally, the autophagy inhibitor 3‑methyladenine abrogated the inhibitory effects of YWHAH knockdown on migration and invasion, and the autophagy inducer rapamycin reversed the promoting effects of YWHAH overexpression...These findings underscore the role of YWHAH as a critical regulator of CRC progression and suggest it as a potential therapeutic target. Interventions targeting YWHAH or its downstream factors may provide innovative approaches for treating CRC, particularly by modulating autophagy to inhibit tumor growth and metastasis."

Journal • Colorectal Cancer • Oncology • Solid Tumor • ATG7 • YWHAH

The skin hydration and anti-ageing benefits of Ectoine, achieved through enhanced Src-ERK-mediated HAS-2 and JNK-driven AQP-3 expression in human keratinocytes, along with the inhibition of MMP-1-induced collagen-I degradation in human fibroblasts, both with and without UVB irradiation. (PubMed, Int J Cosmet Sci) - "We demonstrated that Ectoine exerts skin hydration effects without or with UVB exposure in human skin keratinocyte (HaCaT) cells and anti-ageing in fibroblast (Hs68) cells. Therefore, Ectoine could serve as a potential natural compound in cosmetic preparations for skin hydration and anti-ageing."

Journal • MAPK1 • MMP1