SB202190 / Amgen - LARVOL DELTA

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

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

IL-33 Induces Paneth Cell Production of EGF and Soluble ST2, Regulating Epithelial Regeneration after Intestinal Injury (ASH 2023) - "Furthermore, treatment of intestinal organoids with IL-33 induced EGF mRNA and protein expression, both of which were abrogated by the p38 inhibitor SB202190...Finally, to investigate the importance of this radiation-induced EGF upregulation, WT mice were treated with the EGFR inhibitor gefitinib following irradiation, which resulted in more severe radiation-induced ISC loss, similar to IL-33 deficiency...These findings reveal an unknown pathway of stem cell niche regulation and crypt regeneration whereby the Paneth cell niche responds dynamically upon injury by upregulating EGF and the stem cells orchestrate regeneration by regulating their niche with IL-33. This regenerative circuit also highlights the breadth of IL-33 activity beyond immunomodulation and the therapeutic potential of EGF administration for treatment of intestinal injury."

Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Transplantation • IL33 • LYZ • OLFM4 • THY1

The c-MAF/SLP76 Axis Modulates Immune Evasion and Drives Malignancy in Multiple Myeloma Via Epigenetic Reprogramming (ASH 2024) - "The use of ERK or p38 inhibitors (STE-MEK1 or SB 202190) enhances the suppression of PDL1 by SLP76 knockdown...Knockdown of c-MAF reduced H3K27ac deposition, indicating that c-MAF-mediated super-enhancer remodeling establishes the c-MAF-SLP76-PDL1 axis to modulate immune responses and drive MM malignancy. In summary, we demonstrate that c-MAF plays a non-canonical role in epigenetics, which is related to the regulation of cellular immune status, and suggest that immunotherapy combined with MAPK-targeted therapy represents a novel therapeutic direction for t(14; 16) multiple myeloma."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • BRD4 • CCND2 • LAG3 • LCP2 • MAF • MBD4 • MED1 • NR2C2 • TIGIT • TUBB • TXNIP

Histamine regulates the activity and the expression of the Na+/H+ exchanger (NHE)3 in human epithelial HK-2 cells. (PubMed, Inflamm Res) - "Histamine shows early (within 60 min) and late (48 h) effects on NHE3 expression. The histamine H1 and H4 receptors are shown to contribute to these effects differentially. The findings of this study extends the evidence for a direct contribution of histamine on the renal reabsorptive machinery."

Journal

Potentiation of acid-sensing ion channel currents by EGF/EGFR signaling in rat dorsal root ganglion neurons. (PubMed, Biochem Pharmacol) - "In contrast, the JNK inhibitor SP600125 and the p38 inhibitor SB202190 had no effect on the EGF-mediated potentiation. Finally, injection of EGF into rat paws exacerbated acid-induced nociceptive behavior in dose-dependent manner. The present results that enhanced functional activity of ASICs by EGF/EGFR signaling provided evidence that EGF/EGFR signaling is a promising target for the treatment of pain caused by tissue acidification."

Journal • Preclinical • Pain

Sustained release of dual p38 inhibitors via supramolecular hydrogels to enhance cardiac repair after MI/R injury. (PubMed, Biomaterials) - "Herein, we describe the design of a hydrogelator Nap-Phe-Phe-Thr-Gly-Tyr-OH (Nap-TGY) to coassemble the p38 inhibitor SB202190 (SB), a p38 responsive supramolecular hydrogel (Gel Nap-TGY + SB) for local administration and p38 responsive release of SB to efficiently improve the inflammatory microenvironment...Intramyocardial hydrogel injection significant reducing p38 activation, ROS levels, and inflammation while promoting macrophage reprogramming and angiogenesis. These findings demonstrate a novel therapeutic strategy for ischemic cardiomyopathy through targeted regulation of the p38 mitogen-activated protein kinase (MAPK) pathway, combined with synergistic antioxidant effects and immune reprogramming to restore tissue homeostasis."

Journal • Cardiomyopathy • Cardiovascular • Inflammation • Myocardial Ischemia • Reperfusion Injury

Estrogen-mediated corneal collagen degradation in keratoconus. (PubMed, iScience) - "Our model showed that both corneal epithelium and fibroblasts synthesize their own estrogen, and β-estradiol treatment via p38 MAP kinase pathway regulates MMP2-mediated collagen fiber degradation. p38 MAP kinase inhibitor SB202190 significantly reduced β-estradiol-induced MMP activity and collagen breakdown, as well as cytokine regulation suggesting a potential therapeutic approach."

Journal • Oncology • Ophthalmology • IGFBP3 • MMP2 • PLA2G2A • TNFA

PERK activation mediates neuroprotection against chronic unpredictable stress-induced neurobehavioral changes via the TFEB pathway. (PubMed, Pharmacol Biochem Behav) - "It was also observed that these neuroprotective effects of SB202190 were significantly abolished by pre-treatment with eltrombopag (50 mg/kg, p.o.), a TFEB inhibitor, which signifies the involvement of TFEB signalling in protective mechanism of SB202190 that may have resulted in enhancement of TFEB-mediated autophagy. Therefore, this study highlights the critical role of PERK- TFEB pathway in neuroprotection as well as highlights mechanism and therapeutic potential of SB202190 in alleviating neurobehavioral changes and memory dysfunction associated with chronic unpredictable stress."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • Depression • Inflammation • Mood Disorders • Pain • Psychiatry • TFEB

Neuroprotective Role of THBS2 in Experimental Spinal Cord Injury Via its Anti-neuroinflammatory and Anti-apoptotic Properties. (PubMed, Biochem Genet) - "To investigate the effect of THBS2 on SCI models, THBS2- expressing plasmid/THBS2-siRNA/SB 202190 (p38MAPK pathway inhibitor)/p38 agonist was applied to the rat SCI models and PC12 cell SCI model...In addition, THBS2 down-regulation further promote LPS-induced apoptosis and inflammatory response in PC12 cells. THBS2 was highly expressed in SCI, and overexpression of THBS inhibited the activation of the MAPK signaling pathway and thus protects against SCI."

Journal • CNS Disorders • Inflammation • Orthopedics • IL1B • IL6 • THBS2 • TNFA

The Biofunctional Monomer, the Calcium Salt of 4-Methacryloxyethyl Trimellitic Acid, Promotes Odontoblast Differentiation in Three-Dimensional Culture System. (PubMed, Int J Biomater) - "After treating the cells with the three MAPK inhibitors, the ability of CMET to stimulate ALP activity in MDPC-23 cells was totally suppressed to control levels by the p38 inhibitor, SB202190...The results demonstrated that the biofunctional monomer CMET induced proliferation, differentiation, and mineralization of odontoblast-like cells in a 3D culture system using type I collagen gel at a concentration of 0.3%. Thus, combining CMET and type I collagen gel as a scaffold does not exhibit apparent cytotoxicity and is suggested to have immense potential for dentin regeneration."

Journal

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

Oxidized Phosphatidylcholines Induce Map Kinase-dependent Production of Inflammatory Mediators in Human Airway Fibroblasts (ATS 2025) - "Some cultures also received the TRPA1 antagonist, A967079 (1µM)...Some cultures also received inhibitors of p42/p44 or p38 MAPK (U0126 and SB202190, 10μM)... OxPAPC induce inflammatory gene expression and release in HAF by triggering integrated signaling pathways involving TRPA1 and MAPKs. These data further support a role for OxPAPC as a mediator of oxidative stress that promotes the contributions of airway structural cells such as HAF to airway inflammation and remodeling"

Asthma • Immunology • Inflammation • Respiratory Diseases • CXCL8 • IL6

Heme oxygenase 1 (HO-1) is a drug target for reversing cisplatin resistance in non-small cell lung cancer. (PubMed, J Adv Res) - "The Nrf2/HMOX1 pathway is a significant contributor to cisplatin resistance in NSCLC. Targeting HO-1 with SB 202190 and NDGA presents a promising strategy to overcome resistance and improve chemotherapy outcomes."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HMOX1

LncRNA BANCR/miR-15a/MAPK1 Induces Apoptosis and Increases Proliferation of Vascular Smooth Muscle Cells in Aortic Dissection by Enhancing MMP2 Expression. (PubMed, Cell Biochem Biophys) - "The involvement of the p38 MAPK pathway was examined using the inhibitor SB202190...The LncRNA BANCR/miR-15a-5p/MAPK1 axis forms a ceRNA network that modulates MMP2 expression through the p38 MAPK signaling pathway in vascular smooth muscle cells. BANCR overexpression activates p38 MAPK phosphorylation, leading to enhanced MMP2 expression and subsequent increases in cell proliferation, migration, and apoptosis."

Journal • MAPK1 • MIR15A • MMP2

Resiquimod induces a mixed Th1 and Th2 response via STAT1 and STAT3 signalling in chickens. (PubMed, Biochem Biophys Rep) - "SB202190, IC-87114, and fludarabine phosphate suppressed the R-848-induced expression of MAPK14, PIK3CD, and STAT1, respectively, while chloroquine decreased STAT3 expression. These results align with transcriptomic findings and highlight the upregulation of STAT1 and STAT3 as potential contributors to the induction of Th1 and Th2 immune responses by R-848 in chickens. These insights provide a foundation for optimizing R-848 as an immunomodulatory agent in avian species."

Journal • GATA3 • LRRK2 • MAP3K8 • MAPK1 • MAPK11 • MAPK14 • PIK3CD • STAT1 • STAT3