SB202190 / Amgen - LARVOL DELTA

Interleukin-1β potentiates transforming growth factor-β-induced fibronectin expression, migration, and invasiveness of mesenchymal-like SK-Hep1 cells via p38 mitogen-activated protein kinase-SMAD2/3 crosstalk. (PubMed, Mol Biol Rep) - "These results indicate that IL-1β enhances TGF-β1-mediated mesenchymal phenotypes in SK-Hep1 cells via the activation of a p38 MAPK pathway that is associated with TGF-β/SMAD signaling. Considering that inflammation accelerates HCC progression and metastasis by enhancing the mesenchymal phenotype, these findings support further investigation of anti-inflammatory strategies for HCC management."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • CDH2 • FN1 • IL1B • SMAD2 • TGFB1

SB202190 alleviates endometrial fibrosis by modulating the TGF-β/Smad signaling pathway. (PubMed, Am J Transl Res) - "SRI-011381 significantly reversed the effects of SB202190 on fibrosis and EMT in the cell model. These findings suggest that SB202190 alleviates fibrosis and inflammation and inhibits EMT in IUA models by suppressing the TGF-β/Smad signaling pathway."

Journal • Fibrosis • Immunology • Inflammation • TGFB1

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

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

FGF7 mitigates airway inflammation and epithelial injury in cigarette smoke-induced COPD model. (PubMed, Front Immunol) - "In the CSE-injured 16HBE cell model, recombinant FGF7 was applied with or without SB202190 (a p38 inhibitor), LY294002 (a PI3K inhibitor), or AG1478 (an EGFR inhibitor) to evaluate cell viability, migratory capacity, cytokine production, and activation of corresponding signaling pathways. It mitigates CS-induced airway epithelial damage and inflammation through the ADAM17-dependent EGFR-ERK1/2 axis, p38, and PI3K/AKT pathways. FGF7 therefore emerges as a promising therapeutic target for interventions aimed at preventing airway remodeling in COPD."

Journal • Chronic Obstructive Pulmonary Disease • Fibrosis • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • ADAM17 • FGF7 • IL1B • IL6 • TGFB1 • TNFA

Loss of PINK1 causes age-dependent mitochondrial trafficking deficits in nigrostriatal dopaminergic neurons via aberrant p38 MAPK activation. (PubMed, NPJ Parkinsons Dis) - "Treatment with a calcium channel blocker and p38 inhibitor SB202190 restored mitochondrial motility and increased anterograde transport. Together, our findings suggest that PINK1 loss disrupts mitochondrial trafficking by disturbing calcium and redox homeostasis via the p38 pathway, contributing to PD pathogenesis."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Septins regulate kinase-inhibitor induced micron-scale vacuolation. (PubMed, Exp Cell Res) - "FCF inhibited vacuolation induced by SB202190, PIKFYVE inhibitors and VE-821. Unlike bafilomycin, which inhibits vacuolation with parallel blockade of autophagic proteolysis, FCF mediated suppression of vacuoles doesn't involve accumulation of autophagy markers. The role of septins in micron scale vacuolation may be linked to their role in endosome maturation and septins may contribute towards the cell-type specificity of micron-scale vacuolation."

Journal • Targeted Protein Degradation • CD63 • SEPTIN7 • SEPTIN9

Development and characterization of functional sheep endometrial luminal epithelial organoids. (PubMed, Vet Res) - "However, existing models face significant limitations: conventional two-dimensional (2D) cultures fail to recapitulate endometrial complexity, while current organoid systems are predominantly derived from glandular epithelium. Herein, we report the establishment of a robust three-dimensional (3D) culture system for generating ovine endometrial luminal epithelial organoids using an optimized expansion medium (ExM) supplemented with CHIR99021, Y-27632, SB202190, and the EphrinA1 ligand...Functional validation demonstrated the organoids' capacity to promote blastocyst expansion and trophoblast proliferation in co-culture systems, as well as substrate-specific adhesion that was enhanced by β-estradiol (E2) + medroxyprogesterone acetate (MPA) treatment. Notably, we identified erythropoietin-producing hepatocellular receptor A (EphA) signaling as a novel regulator of stemness properties during organoid development...."

Journal • EFNA1 • EPCAM • KRT18 • KRT18

CILP2 exacerbates diabetes-induced muscle atrophy by over-activating skeletal muscle autophagy and inflammation via the P38 MAPK pathway. (PubMed, Int Immunopharmacol) - "CILP2 upregulation exacerbated the diabetes-induced muscle atrophy by activating autophagy and inflammation through the P38 MAPK pathway, thereby proposing its inhibition as a promising therapeutic strategy."

Journal • Diabetes • Inflammation • Metabolic Disorders • Muscular Atrophy • Type 2 Diabetes Mellitus • FBXO32 • IL1B • IL6 • TNFA

Developing zebrafish avatars for pediatric sarcomas to support functional precision oncology (AACR 2026) - "CellTiter-Glo assays at 34 °C, the incubation temperature required for zPDX experiments, confirmed that RD cells retain drug sensitivity under these conditions: dactinomycin (DAC) significantly reduced RD viability at low nanomolar concentrations (≥10 nM), whereas vincristine (VIN) was effective at 2-10 nM...Guided by media described for zPDX, we developed an enriched medium containing HEPES, glutamine, MEM-NEAA, B27, nicotinamide, ITS, Y-27632, SB202190, N-acetylcysteine, and EGF/FGF with reduced serum...Together, these preliminary data define robust survival and engraftment parameters for RMS xenografts in zebrafish, validate the feasibility of this platform for rapid chemotherapy response readouts, and establish an optimized injection medium that enables even challenging sarcoma subtypes to persist in vivo. These advances provide the foundation for extending this platform to primary pediatric sarcomas, including osteosarcoma, to generate zebrafish avatars for..."

Clinical • Oncology • Osteosarcoma • Rhabdomyosarcoma • Sarcoma • Solid Tumor • FGF

Organoids from primary human prostate cancer exhibit heterogeneity in the states of tumor-associated epithelial cells (AACR 2026) - "For this, we used 9 fresh prostatectomy tissue samples that were processed by mechanical dissection and enzymatic digestion, then filtered and cultured in advanced DMEM/F12 medium with supplements (GlutaMAX, B27, N-acetylcysteine, recombinant EGF, FGF-10 and FGF-2, A-83-01, SB202190, nicotinamide, DHT, PGE2, Y-27632, Noggin, and R-spondin)...We verified through characterisation that the organoids presented a morphology and tumour immune profile similar to the tissues of origin. In summary, we have successfully established and characterised long-term patient-derived PCa organoids, which closely recapitulate the original tumours, providing a robust platform for future pre-clinical studies and precision oncology applications."

Heterogeneity • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • FGF10 • FGF2 • RSPO1 • SPON1

FGFR2 is a Candidate Immune-Associated Marker of Diabetic Foot Ulcer That Promotes Keratinocyte Function by Activating the PI3K/Akt and MAPK Pathways. (PubMed, Mediators Inflamm) - "FGFR2 is lowly expressed in DFU and can exert a protective effect by activating the PI3K/Akt pathway. It is a candidate diagnostic biomarker and potential therapeutic target for DFU."

Journal • Diabetes • Metabolic Disorders • Oncology • FGFR2 • IL6 • TNFA

Giardia duodenalis cysts induce bovine neutrophil extracellular trap formation. (PubMed, Vet Parasitol) - "NET formation was concentration-dependent and required signaling through NADPH oxidase, ERK, p38 MAPK, P2X1 receptor, and PAD4, as shown by specific pharmacological inhibition (DPI, U0126, SB202190, NF449, Cl-amidine; p < 0.01). Additionally, autophagy played a critical role: autophagy inhibitors (3-methyladenine, wortmannin) significantly suppressed NET formation (p < 0.0001), while the autophagy inducer rapamycin had no effect. Immunofluorescence revealed the formation of autophagosomes concurrent with NET formation upon cyst stimulation. These results suggest that extracellular protozoa such as G. duodenalis can induce NET formation via coordinated activation of autophagy and multiple signaling pathways, providing novel insights into host-parasite interactions and potential therapeutic targets."

Journal • ELANE

p38-mediated EZH2 phosphorylation at T367 regulates HER2 pathway in triple negative breast cancer (AACR 2024) - "Vector and EZH2-KD rescue MDA-MB-231 cells were treated with anti-HER2 (trastuzumab or pertuzumab 100 ug/ml) followed by Hoestch proliferation assays. TNBC cells were treated with vehicle, EZH2 inhibitor (EPZ-6438, 20uM), p38 inhibitor (p38i, SB202190, 20uM), EPZ+p38i, anti-HER2 (100 ug/ml), and EPZ+p38i+anti-HER2, followed by Hoestch cell proliferation assays. EZH2-T367A deregulates the expression of a 94-gene network of HER2 pathway genes including EREG, SERPINB5, MERTK, IL6R, SOCS3, and FASCN1 compared to EZH2-WT... We demonstrate that T367 phosphorylation mediates the effect of EZH2 on HER2 signaling in TNBC. Our data support a role for pEZH2-T367 in maintaining the HER2-negative phenotype in and suggest that blocking this phosphorylation event may render TNBC tumors amenable to anti-HER2 treatment strategies."

Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • EREG • HER-2 • IL6R • MERTK • SERPINB5 • SOCS3

The role of estrogen-dependent activation of p38 MAPK signaling pathway in inflammatory breast cancer (AACR 2024) - "In addition, treatment using SB202190, a potent p38 inhibitor, caused a significant decrease in cell viability of several breast cancer cell lines in a dose-dependent manner. Ongoing studies include assessing the effects of p38 inhibition proliferation, invasion, and migration. In summary, a better characterization of the effect of E2 and p38 activation in ER-negative cell lines may provide great insight into novel targeted therapies for IBC."

Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Inflammatory Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

Kinase inhibitors in organoid media influence Toxoplasma gondii growth and development. (PubMed, Microbiol Spectr) - "We found that low concentrations of SB202190 (a p38 MAPK inhibitor) and A83-01 (an ALK 4/5/7 receptor inhibitor) are each sufficient to alter T. gondii growth even in fibroblast cells...This study improves our understanding of the Toxoplasma gondii lifecycle in one of those systems. It also serves as a template for other pathogen researchers to consider influences within their own systems."

Journal • ALK

From clinical evidence to biological mechanisms: GPRC5B as a key mediator of metabolic syndrome-associated prostate cancer. (PubMed, Int J Biol Macromol) - "In vivo, endothelial GPRC5B deficiency significantly accelerated tumor growth and neovascularization, phenotypes that were effectively reversed by the p38 inhibitor SB202190. Clinical specimens corroborated reduced GPRC5B expression and increased microvessel density in MetS-associated PCa. Collectively, our findings establish endothelial GPRC5B downregulation as a key molecular driver promoting pathological angiogenesis via the MKK3/6-DUSP1-p38 axis, suggesting that targeting this signaling cascade offers a promising therapeutic strategy for managing MetS-associated PCa aggression."

Journal • Genito-urinary Cancer • Metabolic Disorders • Oncology • Prostate Cancer • Solid Tumor • DUSP1 • MAP2K3

Oridonin Regulates Pituitary-derived Folliculostellate Cells Apoptosis via the p38 MAPK/p53 Signaling Pathway. (PubMed, Eur J Pharmacol) - "The p38 MAPK inhibitor SB202190 reversed ORI-induced effects on cell death, cell migration and invasion, and apoptosis, highlighting the critical role of the p38 MAPK/p53 pathway. ORI effectively suppressed subcutaneous tumour growth in nude mice without notable toxicity while upregulating apoptosis-related proteins Bax and cleaved caspase-3 and downregulating Bcl-2 through activation of the p38 MAPK/p53 pathway."

IO biomarker • Journal • Oncology • Pituitary Gland Carcinoma • BCL2 • CASP3

A small molecule strategy with forskolin and p38 inhibitor for serum-free muscle stem cell expansion. (PubMed, NPJ Sci Food) - "Subsequent synergistic screening revealed that the p38 inhibitor SB202190 enhanced forskolin's effects...Transcriptomic analysis revealed that the Beefy-F + S medium broadly altered the bMuSC transcriptome to maintain myogenic identity, upregulate cell cycle genes, and reshape extracellular matrix (ECM) pathways, with forskolin sustaining myogenic factors and the p38 inhibitor promoting proliferation and modulating ECM interactions. Overall, this study establishes a cost-effective, small molecule-based strategy for the robust serum-free expansion of bMuSCs."

Journal • PAX7

Necessary, Legendary and Detrimental Components of Human Colorectal Organoid Culture Medium: Raising Awareness to Reduce Experimental Bugs. (PubMed, Cancers (Basel)) - "SB202190, A83-01 and vanadate (from advanced DMEM-F12) modify intracellular signaling. N-AcetylCysteine and Primocin modify the redox response and mitochondrial metabolism, respectively. Thus, the unintentional addition of these molecules to the organoid medium introduces biases under specific experimental settings. While the original organoid medium formula is the gold standard for propagating organoids in vitro, more focused, reliable conditions are necessary for specific organoid-based tests."

Journal • Review • GAST

Persistent Suppression of Phrenic Motor Plasticity after Mild Acute Systemic Inflammation in Adult Rats. (PubMed, Function (Oxf)) - "Contrary to 24 hours, at 1-week post-LPS, spinal A2A receptor inhibition (MSX-3) failed to restore pLTF, while spinal p38 MAPK inhibition (SB202190) rescued pLTF at both 24 hours and 1-week post-LPS. These findings suggest that distinct mechanisms underlie pLTF suppression at 24 hrs vs 1-week post-LPS, although both mechanisms share downstream p38 MAPK signaling. Since mAIH is emerging as a therapeutic modality to improve respiratory and non-respiratory motor function in people with neurological disorders, targeting p38 MAPK may prevent persistent plasticity suppression in individuals with a history of inflammation."

Journal • Preclinical • CNS Disorders • Inflammation • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Apnea • Sleep Disorder • ADORA2A

Starvation of leukemic cells enhances DNA damage-induced apoptosis in vitro via ROS/p38 MAPK and prevents leukemia progression in fasting xenograft mice. (PubMed, J Biol Chem) - "The resulting augmented cell death was inhibited both by the ROS scavenger N-acetyl cysteine (NAC) and the p38 MAPK inhibitor SB 202190. The translational potential of increasing the efficacy of DNA damaging agents in starving ALL cells was supported by in vivo data showing that intermittent fasting, combined with subtherapeutic doses of irradiation, significantly inhibit the leukemia progression in a xenograft model of severe combined immunodeficiency (SCID) mice."

Journal • Preclinical • Acute Lymphocytic Leukemia • Genetic Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology • Primary Immunodeficiency

Dehydrocorybulbine blocks the Lyn-mediated MAPK pathway to promote anti-inflammatory polarization of microglia in mice after sevoflurane anesthesia. (PubMed, Brain Res) - "Similarly, p38 MAPK signal inhibitor SB 202190 opposed the proinflammatory polarization of BV2 cells and inflammatory damage mediated by Lyn overexpression. In conclusion, our study demonstrates that DHCB inhibits Lyn expression in microglia, thereby suppressing p38 MAPK signal transduction and accelerating the polarization of microglia from M1 to M2 phenotype to alleviate sevoflurane-induced POCD."

Journal • Preclinical • Alzheimer's Disease • Anesthesia • Cognitive Disorders • Pain • LCK • LYN

NFATc1 activates the Ras/Raf/p38 MAPK pathway to promote the progression of lung adenocarcinoma. (PubMed, Transl Cancer Res) - "Pretreatment with the inhibitor SB202190 decreased the expression of proteins related to Ras/Raf/p38 MAPK and significantly suppressed the proliferation, migration, and invasion of A549 cells...NFATc1 is highly expressed in LUAD tissues, and its expression level is closely related to clinical characteristics. NFATc1 may promote the proliferation, migration, and LUAD cell invasion via the Ras/Raf/p38 MAPK pathway, providing a new therapeutic target for LUAD."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • NFATC1

Osteopontin Promotes Liver Echinococcus multilocularis Growth and Invasion via p38MAPK Pathway. (PubMed, Parasite Immunol) - "The mice in the anti-p38MAPK group and the anti-p38MAPK + LV-OPN-0423 group were then given SB202190 (this is an inhibitor of p38MAPK) for 4 weeks, and the mice in each group were injected with corresponding lentivirus diluent once a week for 8 weeks...The OPN level promoted the expression of p38MAPK and p-p38MAPK. These results suggested that OPN could regulate Em's growth and metastasis through the p38MAPK signalling pathway in host hepatocytes, providing evidence that OPN and p38MAPK may be novel molecular targets for treating alveolar echinococcosis."

Journal • Hepatocellular Cancer • Infectious Disease • Oncology • SPP1