SB202190 / Amgen - LARVOL DELTA

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

Tetrahydrocurcumin exhibits neuroprotective effects by inhibiting neuron ferroptosis via activity of iPLA2β/p38 MAPK phosphorylation in rat TBI model. (PubMed, Free Radic Res) - "In addition, SB202190 which is an inhibitor of p38 could enhance THC protection and lessen formation of ferroptosis related proteins in cells. In conclusion, these findings suggested that THC may promote neurological function recovery after TBI by inhibiting neuron ferroptosis via activity of iPLA2β/P-p38."

Journal • Preclinical • CNS Disorders • Inflammation • Vascular Neurology

Kinase Inhibitor-Induced Cell-Type Specific Vacuole Formation in the Absence of Canonical ATG5-Dependent Autophagy Initiation Pathway. (PubMed, Mol Cell Biol) - "A screen for modulators of SB202190-induced vacuolation revealed molecules including multi-kinase inhibitor sorafenib as inhibitors of vacuolation and sorafenib co-treatment enhanced cytotoxicity of SB202190. To identify the factors determining the cell-type specificity of vacuolation induced by SB-compounds and VE-821, we compared the transcriptomics data from vacuole-forming and non-vacuole-forming cancer cell lines and identified a gene expression signature that may define sensitivity of cells to these small-molecules. Further analyses using small molecule tools and the gene signature discovered here, could reveal novel mechanisms regulating this interesting anti-cancer phenotype."

Journal • Oncology • ATG5 • MAPK1 • MAPK11 • MAPK14

The protective effect of irisin against hemorrhagic injury is mediated by PI3K and p38 pathways in hemorrhage/resuscitation. (PubMed, J Pharmacol Exp Ther) - "Experimental groups were divided based on the different treatments during resuscitation as follows: (1) hemorrhage: adult male CD-1 mice were subjected to hemorrhage at a mean arterial blood pressure of 35-45 mm Hg for 60 minutes, followed by resuscitation with shed blood and lactated Ringer's solution (n = 13); (2) hemorrhage + irisin: receiving irisin (5 μg/kg; n = 13); (3) hemorrhage + irisin + PI3K inhibitor: receiving both Ly294002 (1 mg/kg, i.v.) and irisin (n = 6); and (4) hemorrhage + irisin + p38 inhibitor: receiving SB202190 (1 mg/kg, i.v.) and irisin (n = 6). SIGNIFICANCE STATEMENT: This study has identified a critical pathway in the regulation of trauma/hemorrhage by using a preclinical trauma model, in which irisin, as a hormone factor, stimulates PI3K and p38 pathways to induce protection against traumatic conditions. The study holds promise for developing a new therapeutic strategy to target irisin and..."

Journal • Hematological Disorders • Oncology • IL6 • TNFA

Design, synthesis, and in silico studies of new quinazolinones tagged thiophene, thienopyrimidine, and thienopyridine scaffolds as antiproliferative agents with potential p38α MAPK kinase inhibitory effects. (PubMed, RSC Adv) - "Employing the standard MTT assay, every target compound's in vitro antiproliferative efficacy was evaluated in comparison with doxorubicin against both normal WI-38 cells and various cancer cell lines...The in vitro enzyme assay showed that the new analogues had a better ability to inhibit p38α MAPK kinase than SB 202190 (IC50s = 0.18 ± 0.02, 0.23 ± 0.05, 0.31 ± 0.04, and 0.27 ± 0.06 μM, respectively)...Based on the molecular docking study, candidates 6, 8a, and 8b all fit well within p38α MAPK kinase, with energy scores of -10.88, -11.28, and -10.96 kcal mol-1, respectively. Based on the in silico computer examination of physico-chemical and ADMET properties, the latter analogues seem to be promising candidates for further development and optimization in research."

Journal • Oncology • BCL2 • CASP3

Mustard Gas Induced Corneal Injury Involves Ferroptosis and p38 MAPK Signaling. (PubMed, Invest Ophthalmol Vis Sci) - "The hCSFs were exposed to nitrogen mustard (NM; SM analogue) at various timepoints (30 minutes, eight hours, and 24 hours). A p38 MAPK specific inhibitor, SB202190, was also used...The inhibition of p38 MAPK promoted cell survival and reduced ROS production following mustard gas exposure. The results of in vivo and in vitro investigations uncovered a novel mechanism that mustard gas toxicity to the cornea involves ferroptosis pathway and p38 MAPK activation."

Journal • Corneal Abrasion • ACSL4 • GPX4 • SLC7A11

Cigarette smoke extract induces p38-mediated expression and ROS/rho-mediated translocation of alpha 2C adrenoceptor in human microvascular smooth muscle cells. (PubMed, Prog Cardiovasc Dis) - "This increase is associated with the activation of p38 MAPK, as pretreatment with SB-202190, a p38 specific inhibitor, attenuated CSE-induced α2C-AR expression...We also show that CSE induces translocation of vascular α2C-AR to the plasma membrane, and that this mobilization is attenuated by inhibiting ROS via N-acetylcysteine or apocynin...While CSE activates a p38-dependent mechanism to increase α2C-AR expression, it initiates the receptor's spatial and functional rescue via a ROS/RhoA signaling pathway. These results provide mechanistic insight into the effect of cigarette smoking on RP, and further reinforce that smoking avoidance/cessation is critical to manage this disease, especially in the absence of a definitive drug for RP."

Journal • Cardiovascular • Rheumatology • RHOA

Interleukin-22 promotes endometrial carcinoma cell proliferation and cycle progression via ERK1/2 and p38 activation. (PubMed, Mol Cell Biochem) - "The IL-22-mediated changes in cell proliferation, cycle progression, and protein expression can be effectively inhibited by the ERK1/2 inhibitor U0126 and the p38 inhibitor SB202190...Our findings suggest that IL-22 promotes endometrial carcinoma cell proliferation and G1/S phase progression by activating ERK1/2 and p38 signaling. Therefore, IL-22 may represent a potential therapeutic target for the treatment of endometrial carcinoma."

Journal • Endometrial Cancer • Gynecologic Cancers • Oncology • Solid Tumor • CCND1 • CCNE1 • CDK4 • CDK6 • IL22 • MYC

In vitro hair growth-promoting effects of araliadiol via the p38/PPAR-γ signaling pathway in human hair follicle stem cells and dermal papilla cells. (PubMed, Front Pharmacol) - "Subsequent Western blot analysis and ELISA using inhibitors such as GW9662 and SB202190 confirmed that these hair growth-promoting effects were dependent on the p38/PPAR-γ signaling in both HHFSCs and HDPCs. Araliadiol promotes hair growth through the p38/PPAR-γ signaling pathway in human hair follicle cells. Therefore, araliadiol can be considered a novel drug candidate for the treatment of alopecia."

Journal • Preclinical • Alopecia • Immunology • CCNB1 • CD34 • FGF7 • IGF1

Inhibiting p38α and β MAPK affects testis development in the marsupial tammar wallaby. (PubMed, Sex Dev) - "This study confirms that components of the MAPK pathway drive testis differentiation via the key downstream genes SOX9 and AMH in marsupials as is observed in eutherian mammals."

Journal • SOX9