PD98059 / Wayne State University - LARVOL DELTA

FTO-mediated MMP1 m6A modification promotes osteogenic differentiation of bone marrow mesenchymal stem cells via the ERK pathway in congenital scoliosis. (PubMed, Sci Rep) - "A specific ERG inhibitor called PD98059 prevents MMP1-mediated promotion. Additionally, our research revealed that FTO affects how BMSCs can differentiate in CS patients by regulating MMP1 levels. FTO-mediated MMP1 m6A modification underlies MMP1's promotion of osteogenic differentiation via the ERK pathway, implying that it could be a viable treatment target for CS."

Journal • Genetic Disorders • Obesity • FTO • MMP1

Piperine Induces Apoptosis and Cell Cycle Arrest via Multiple Oxidative Stress Mechanisms and Regulation of PI3K/Akt and MAPK Signaling in Colorectal Cancer Cells. (PubMed, Antioxidants (Basel)) - "Pretreatment with antimycin A, apocynin, allopurinol, and PD98059, and the overexpression of p-Akt significantly recovered cell viability and reduced apoptosis, confirming the involvement of these pathways. This study is the first to demonstrate piperine induces apoptosis in CRC cells through a multifaceted oxidative stress mechanism and by critically modulating PI3K/Akt and ERK signaling pathways."

Journal • Colorectal Cancer • Oncology • Solid Tumor

PACAP/PAC1R activation promotes group 2 innate lymphoid cells-dependent allergic rhinitis via ERK pathway. (PubMed, Arch Biochem Biophys) - "These effects were effectively reversed by ERK inhibitor PD98059. Importantly, both PAC1R knockdown and ERK inhibition significantly decreased p-ERK expression and ILC2s proliferation, while ameliorating AR pathological features. Our findings revealed that PACAP/PAC1R activation promoted ILC2s proliferation and allergic inflammation through ERK pathway, which provides novel insights into the regulation of ILC2s and potential therapeutic targets in allergic rhinitis."

Journal • Allergic Rhinitis • Contact Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • ADCYAP1 • IL13 • IL5 • MAPK1

Role and mechanism of IGFBP5 in the real-ambient particulate matter exposure-induced chronic lung injury. (PubMed, Front Pharmacol) - "Co-treatment with si-IGFBP5 and ERK1/2 signaling pathway inhibitor PD98059 could further aggravate the production of ROS in cells...We found that the upregulated hsa-miR-33a-5p repressed IGFBP5 translation by forming a silencing complex with Argonaute protein 2 (AGO2) in a real-ambient PM exposure system, which further led to the suppression of the ERK1/2-SOD2 signaling pathway and increased levels of ROS. This study revealed that the downregulation of IGFBP5 promoted oxidative damage in lung cells by inhibiting the IGFBP5-ERK1/2-SOD2 pathway, and targeted inhibition of hsa-miR-33a could alleviate PM-induced lung injury by upregulating IGFBP5."

Journal • Inflammation • Respiratory Diseases • IGFBP5 • MIR33A • SOD2

Development of a novel PIK3CA-mutated pancreatic tumor mouse model and evaluation of the therapeutic effects of a PI3K inhibitor. (PubMed, PLoS One) - "Combination treatment with alpelisib and the MEK inhibitor PD98059 significantly inhibited cell proliferation. These data indicate that PIK3CA mutation may be oncogenic in PDAC and that PI3K inhibitors can be effective against such tumors. Dual inhibition of the PI3K/AKT and MEK/ERK pathways may enhance therapeutic effects in PI3K/AKT-activated pancreatic tumors."

Journal • Preclinical • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Transplantation • PIK3CA

The truncated isoform of the receptor for hyaluronan-mediated motility (RHAMMΔ163) modulates shelterin and telomerase reverse transcriptase transcription affecting telomerase activity. (PubMed, Front Aging) - "Increasing Tert mRNA expression by blocking leucine zipper sequence with function-blocking RHAMM peptide NP-110 in a TERT-deficient mouse model of idiopathic pulmonary fibrosis, alongside suppressing Tpp1 and Pot1a expression in mouse embryonic fibroblasts using ERK1 inhibitor PD98059, highlights the importance of the HATABD domain (amino acids 718-751), which includes leucine zipper and ERK-binding sequences at the C-terminus of mouse RHAMM in regulating telomerase function. Increased telomerase activity raised Hmmr expression, suggesting a potential feedback loop between RHAMM and TERT expression. Taken together, this report provides the first evidence that RHAMMΔ163 regulates TERT and shelterin expression and telomerase activity in mammalian cells."

Journal • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • HMMR • TERT • TPP1

Tension Force Stress Downregulates the Expression of Osteogenic Markers and Mineralization in Embryonic Stem-Cell-Derived Embryoid Bodies. (PubMed, Cells) - "While the transfection with si-β-catenin did not affect the osteogenic potency of EBs at a significant level, treatment with 10 μM of PD98059, but not of SP600125 or SB203580, diminished the mineralization of EBs and the expression of RUNX2 and RUNX2-regulated osteoblastic genes. The transfection with si-ERK1, but not with si-ERK2, suppressed the mineralization of osteogenic medium-supplied EBs and the expression of osteoblast-specific genes. Collectively, this study demonstrates that tensile stress inhibits osteogenic potency of EBs by downregulating ERK1-mediated signaling and osteogenic gene expression."

Biomarker • Journal • CTNNB1 • POU5F1 • RUNX2 • SOX2

Mesenchymal stem cell-secreted KGF ameliorates acute lung injury via the Gab1/ERK/NF-κB signaling axis. (PubMed, Cell Mol Biol Lett) - "Our study validated that the efficacy of MSCs in the treatment of edematous ALI was significantly associated with KGF, which potentially enhanced the upregulation of ENaC through the Gab1/ERK/NF-κB signaling pathway."

Journal • Acute Lung Injury • Pulmonary Disease • Respiratory Diseases • GAB1

Impact of IKCa Channels on CD34+ Cells in Arteriole Remodeling in Angiotensin II-Induced Hypertension Model Mice. (PubMed, Hypertension) - "Bone marrow transplantation, the IKCa channel inhibitor TRAM-34, and the ERK (extracellular signal-regulated kinase) inhibitor PD98059 were used to validate functional mechanisms...Arteriole-resident CD34+ cells contribute to endothelial repair in Ang II-induced hypertension. Moreover, IKCa channel upregulation facilitates CD34+ cell migration via ERK/P38 signaling, suggesting potential therapeutic targets for hypertension."

Journal • Preclinical • Bone Marrow Transplantation • Cardiovascular • Hypertension • Transplantation • CD31 • CD34 • PECAM1

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

Jatropholone B from Jatropha curcas inhibits melanin synthesisextracellular signal-regulated kinase activation in Mel-Ab cell. (PubMed, J Tradit Chin Med) - "Based on these results, we suggest that ERK activation by jatropholone B inhibits melanogenesis via the downregulation of MITF and tyrosinase expression. Therefore, jatropholone B from J. curcas can be a candidate for developing a new skin-whitening agent."

Journal • Ophthalmology • CTNNB1 • MITF • Tyrosinase

Vascular Protection of Neferine on Attenuating Angiotensin II-Induced Blood Pressure Elevation by Integrated Network Pharmacology Analysis and RNA-Sequencing Approach. (PubMed, Chin J Integr Med) - "Neferine remarkably alleviates Ang II-induced elevation of blood pressure, vascular dysfunction, and pathological changes in the abdominal aorta. This beneficial effect is mediated by the modulation of multiple pathways, including calcium and ERK1/2 pathways."

Journal • Cardiovascular • Hypertension

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

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

MCPIP1 deficiency alleviates abdominal aortic aneurysm formation by inhibiting MAPK signaling. (PubMed, Biochem Cell Biol) - "Furthermore, inactivation of ERK1/2 with PD98059 reduced Ang II-induced proliferation and migration of VSMCs...KLF4 knockdown reversed the facilitating effect of Ang II on MCPIP1 expression. In conclusion, our findings suggest that MCPIP1 promotes Ang II-induced VSMCs phenotypic switching via the MAPK signaling pathway."

Journal • Cardiovascular • KLF4

Identification of potential diagnostic markers and molecular mechanisms of asthma and ulcerative colitis based on bioinformatics and machine learning. (PubMed, Front Mol Biosci) - "Molecular docking identified several potential therapeutic compounds, with PD 98059, beclomethasone, and isoproterenol validated as promising candidates. The stability of the TIMP1-Beclomethasone complex was determined through molecular dynamics simulations. This study highlights NOS2, TCN1, CHI3L1, and TIMP1 as potential biomarkers and therapeutic targets for asthma and UC, providing insights into shared mechanisms and new strategies for diagnosis and treatment."

Journal • Asthma • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Pulmonary Disease • Respiratory Diseases • Ulcerative Colitis • CHI3L1 • IL17A • NOS2 • TIMP1

DEC1 promotes breast cancer bone metastasis through transcriptional activation of CXCR4. (PubMed, J Biomed Res) - "Notably, AMD3100 (a CXCR4 antagonist) partially reversed the DEC1-OE-induced upregulation of CXCR4 and associated pro-metastatic genes...Furthermore, pharmacological inhibition of AKT (LY294002) or JAK2 (AZD1480), but not ERK (PD98059), attenuated DEC1-mediated CXCR4 upregulation, although all three inhibitors mitigated DEC1-driven migration-related gene expression. Additionally, DEC1 enhanced CXCL12 secretion from mesenchymal stromal cells and osteoblasts, amplifying the CXCR4/CXCL12 axis within the bone microenvironment. Collectively, our findings demonstrate that DEC1 promotes breast cancer (BC) bone metastasis by directly transactivating CXCR4 expression, providing a molecular basis for targeting DEC1 to prevent and treat BC bone metastasis."

Journal • Breast Cancer • Oncology • Solid Tumor • CXCL12 • CXCR4 • JAK2

EXPRESS: TLR3 mediates central sensitization in a chronic migraine model induced by repeated nitroglycerin through the ERK signaling pathway. (PubMed, Mol Pain) - "In addition, we investigated the effects of TLR3 inhibitor(CU CPT4a), MEK inhibitor(PD98059), TRAF6 inhibitor(C25-140), and TAK1 inhibitor (Takinib) on chronic migraine-like behavior, and activation of the ERK pathway in the Trigeminal nucleus caudalis(TNC). Concurrent inhibition of TLR3 function, TRAF6, TAK1, and the ERK pathway counteracted these changes and alleviated hyperalgesia in CM mice. Con-clusions: Our findings suggest that TLR3 may play a role in central sensitization in CM mice by TRAF6-TAK1 axis modulating the ERK signaling pathway."

IO biomarker • Journal • CNS Disorders • Migraine • Neuralgia • Pain • FOS • TLR3 • TRAF6

Interleukin 33 Promotes Liver Sinusoidal Endothelial Cell Dysfunction and Hepatic Fibrosis in Diabetic Mice. (PubMed, Diabetes Metab J) - "Hepatic stellate cell line LX-2 co-cultured with rIL33-pretreated LSECs displayed augmented activation, which was also attenuated by rapamycin or PD98059 pretreated. IL33 drives LSEC dysfunction and promotes diabetic hepatic fibrosis, thus a potential therapeutic target for diabetic liver fibrosis."

Journal • Preclinical • Diabetes • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Metabolic Disorders • Oncology • Type 2 Diabetes Mellitus • IL33 • ST2

Polystyrene nanoplastics exposure induces cognitive impairment in mice via induction of oxidative stress and ERK/MAPK-mediated neuronal cuproptosis. (PubMed, Part Fibre Toxicol) - "This study presents preliminary evidence indicating that PS-NPs may induce neuronal cuproptosis, potentially through the oxidative stress-mediated activation of the ERK-MAPK pathway, which contributes to cognitive dysfunction in mice. These findings provide insights into the potential mechanisms underlying PS-NPs neurotoxicity and highlight possible therapeutic targets, such as copper chelation or MAPK inhibition, for mitigating the neurological risks associated with nanoplastic exposure, pending further validation in human-relevant models."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Movement Disorders • Parkinson's Disease • DLAT • FDX1 • LIAS

Limettin and PD98059 Mitigated Alzheimer's Disease Like Pathology Induced by Streptozotocin in Mouse Model: Role of p-ERK1/2/p-GSK-3β/p-CREB/BDNF Pathway. (PubMed, J Neuroimmune Pharmacol) - "Thus, based on these findings, PD98059 and limettin may have promising effects in protecting against SAD. Using blockers/inhibitory molecules are recommended to confirm effect through the corresponding pathway."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Inflammation • BDNF • IL6

Dexmedetomidine Blocks the ERK Pathway by Inhibiting MAP3K8 to Achieve a Protective Effect in Lung Ischemia/Reperfusion Injury. (PubMed, Kaohsiung J Med Sci) - "Lung ischemia/reperfusion injury (LIRI) is a primary contributor to morbidity and mortality following lung transplantation. Upregulation of MAP3K8 impaired the protective effect of DEX in vivo and in vitro, which was reversed by the ERK inhibitor PD98059. Overall, DEX achieved its protective effect against LIRI by inhibiting the MAP3K8-ERK axis."

Journal • Cardiovascular • Inflammation • Pneumonia • Reperfusion Injury • Transplantation • CDH5 • MAP3K8

Atmospheric carbon monoxide and hospitalization for mental and behavioral disorders: insights from a longitudinal study in Shijiazhuang. (PubMed, Front Psychol) - "Additionally, elevated MAPK3 expression was found in the blood samples of depressed patients, and treatment with the MAPK inhibitor PD98059 alleviated CO-induced depression in a mouse model...The findings suggest that CO exposure may exacerbate mental health conditions, particularly in vulnerable populations. These insights underline the importance of air quality management and highlight potential pathways for therapeutic interventions targeting CO-induced mental health disorders."

Journal • Observational data • Behavior Disorders • CNS Disorders • Depression • Mental Retardation • Mood Disorders • Psychiatry • MAPK3

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