P1/2, N=267, Recruiting, Zhuhai Yufan Biotechnologies Co., Ltd | Trial completion date: Mar 2025 --> Nov 2027 | Trial primary completion date: Nov 2024 --> May 2027

In summary, OMT can antagonise TE-induced cardiac injury and lethal effects by inhibiting the activation of the MAPK pathway and reducing oxidative stress and apoptosis. As a natural compound, OMT offers a potential therapeutic strategy for jellyfish stings.

P1/2, N=40, Recruiting, Zhuhai Yufan Biotechnologies Co., Ltd

No abstract available

No abstract available

P1/2, N=27, Recruiting, Ann & Robert H Lurie Children's Hospital of Chicago

Further, Autophagy inhibits S. suis infection-induced NF-κB and MAPK signaling and subsequent inflammatory factors CCL2, CCL3, CCL5, and TNF-α. Collectively, these findings suggest that AMPK/mTOR-regulated autophagy has an inhibitory effect on pro-inflammatory cytokines and chemokines by regulating the NF-κB and MAPK pathways.

P1/2, N=106, Active, not recruiting, Nimbus Saturn, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Dec 2024 --> May 2025 | Trial primary completion date: Sep 2024 --> Feb 2025

Acupoint injection can reduce nasal allergic symptom, and MUC5AC secretion in rats with allergic rhinitis, alleviate nasal mucosal inflammatory reactions, and its mechanism of action may be related to the inhibition of p38 MAPK phosphorylation, thereby reducing the release of inflammatory factors.

ISAP has a potential inhibiting effect on transplanted tumor in mice, and could maintain the general conditions, physical strength and body weight of mice. The expression levels of RAS, p-ERK, MMP2 and c-myc were also decreased to a certain extent. By inhibiting the expression of upstream proteins, the expression levels of downstream proteins in ERK/MAPK signaling pathway were significantly decreased. Therefore, it can be concluded that ISAP may exert an anti-tumor effect by blocking the ERK/MAPK signaling pathway and inhibiting the expression of MMP2 and c-myc proteins.

In cultured mouse CRC cells, SQYCD selectively upregulated levels of the CRC-associated protein lymphocyte antigen 6 family member G6D, while the AKT activator SC-79 reversed this effect. The discoveries made herein suggest that SQYCD exerts a therapeutic effect in CRC by inhibiting Treg recruitment via inhibition of the AKT/p38α/LY6G6D signaling axis.

Results Compared with the normal tissue,the ccRCC tissue showed up-regulated mRNA and protein levels of PSMB8 (both P<0.001),which were associated with the TNM stage of patients with ccRCC (P<0.001).Compared with the negative control group,overexpression of PSMB8 promoted the proliferation (P=0.021,P=0.039),migration and invasion (all P<0.001) of 786-O and ACHN cells,and the knockdown of PSMB8 inhibited the proliferation (P=0.022,P=0.005),migration and invasion (all P<0.001) of 786-O and ACHN cells.The pathway enrichment analysis of co-expressed genes of PSMB8 predicted the mitogen-activated protein kinase signaling pathway (P<0.001).After the knockdown of PSMB8,786-O and ACHN cells showed lowered phosphorylation levels of MEK1/2 (P=0.017,P=0.016) and ERK1/2 (P=0.010,P=0.040) and down-regulated transcription levels of ERK downstream factors c-Myc (P=0.043,P=0.038),c-Fos (P=0.025,P=0.008),and CyclinD1 (P=0.006,P=0.047).Compared with the ERK agonist C16-PAF group,the PSMB8 knockdown + C16-PAF group showed inhibited proliferation (P=0.003,P=0.002),migration and invasion (all P<0.001) of 786-O and ACHN cells. Conclusion PSMB8 may promote the proliferation,migration,and invasion of ccRCC cells by activating the MEK/ERK signaling pathway.

ARI de-sensitizes Fao cells to stress signaling, while OLA has the opposite effect. These findings contribute to our understanding of the metabolic risks associated with prolonged AAP use and may inform future therapeutic strategies.

An untargeted metabolomics study showed that the levels of 4-hydroxyproline, rhamnose, and cysteine were increased after AM supplementation, and their extending effect on the lifespan and health-span of C. elegans were partly dependent on the pmk-1 gene. In conclusion, our results revealed that AM can promote the lifespan and health-span of C. elegans via the PMK-1 pathway, highlighting the potential of AM as a dietary supplement to delay aging.

MAP3K1 was correlated with the immune infiltration in glioma. MAP3K1 could facilitate the migration and TMZ resistance of GBM cells through MEK/ERK signalling.

Evidence suggests that high BC tissue (Cd, Co, Pb, Ni, Si) concentrations are associated with over-expressed MD genes, OS, p38-MAPK and low SOD2. These findings provide important understanding keys of probable carcinogenic pathways in BC associated with HMTE. So, efforts should be performed to minimize and counteract exposure to toxic HMTE.

Background NDI-101150, an oral, selective, small molecule inhibitor of HPK1, is being studied as monotherapy and in combination with pembrolizumab. Ethics Approval This multicenter study was approved by the relevant Ethics Board at each study site. All participants gave informed consent before taking part.

Treatment of tumor-bearing mice shows T-cell-dependent antitumor efficacy. MAP4K1 inhibition in conjunction with PD-L1 blockade results in a superior antitumor impact, illustrating the complementarity of the single agent treatments.

Compared with the Platycodon grandiflorus + Curcumae Rhizoma group, the Platycodon grandiflorus + Curcumae Rhizoma + U46619 group had significantly decreased IC50, cell colony count, invading cell count and β-catenin, N-cadherin, and vimentin expressions, in addition to elevated E-cadherin protein expression, apoptosis rate, and p-p38 MAPK/p38 MAPK ratio (P < 0.05). Platycodon grandiflorus can reverse the resistance of breast cancer cells to Dox and regulate their biological activities by activating the p38 MAPK signaling pathway.

Compound 24 exhibited favorable mouse and rat pharmacokinetic profiles with reasonable oral exposure. Compound 24 showed potent in vivo anti-tumor activity in a CT26 syngeneic tumor model with 95 % tumor growth inhibition in combination with anti-PD-1.

In addition, compound 3a exhibited favorable metabolic stability in mouse liver microsomes and plasma. Overall, this work provides a structurally novel lead compound for the development of HPK1 inhibitors.

In agreement, clinical data disclose that high KSR1 expression levels correlate with greater metastatic potential and adverse evolution of mammary tumors. Overall, our results portray both ERK dimerization and KSR1 as essential factors for the regulation of cell motility and mammary tumor dissemination.

Treatment with MAPK inhibitors significantly reduced the cytokine induction caused by NSD1 knockdown, with the p38 MAPK inhibitor being more effective than the JNK inhibitor. These findings provide new insights into the role of NSD1 loss in neurological dysfunctions associated with SOTOS.

In conclusion, β-glucan injection resulted in elevated levels of mucous cells, nonspecific immunity, antioxidant capacity, and anti-apoptosis in grouper by modulating the p38 MAPK pathway. This study offers insights into the potential molecular mechanism underlying the protective effects of β-glucan on intestinal health in pearl gentian grouper.

P1, N=11, Terminated, Regor Pharmaceuticals Inc. | N=56 --> 11 | Trial completion date: Aug 2025 --> Feb 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Feb 2025 --> Feb 2024; Due to the change in study plan and not due to safety reasons

No abstract available

P2, N=47, Terminated, BioMed Valley Discoveries, Inc | N=215 --> 47 | Trial completion date: Mar 2025 --> Jul 2024 | Recruiting --> Terminated | Trial primary completion date: Dec 2024 --> May 2024; Lack of Enrollment for Remaining Open Baskets

P1, N=320, Active, not recruiting, Glenmark Specialty S.A. | Recruiting --> Active, not recruiting

This study investigated that the immunostimulatory effects of OM hydrolysates (OMHs) obtained by using various proteolytic enzymes (Alcalase®, bromelain, α-chymotrypsin, Neutrase®, pancreatin, papain, Protamax®, and trypsin) in RAW 264.7 cells. The effect of OMPA on mitogen-activated protein kinase signaling pathway was increased the phosphorylation of p38, c-Jun NH2-terminal kinase, and extracellular signal-regulated kinase in a concentration-dependent manner. Therefore, OMPA could be used as a potential immune-stimulating agent in the functional food industry.

Ulixertinib, a novel targeted agent with no previous pediatric data, was successfully evaluated in a national precision medicine basket trial. The pediatric RP2D of ulixertinib is 260 mg/m2/dose orally twice a day. Limited single-agent efficacy was observed in a biomarker-selected cohort of refractory pediatric tumors.

In conclusion, KHK-6 is a novel ATP-competitive HPK1 inhibitor that blocks the phosphorylation of HPK1 downstream of SLP-76, enhancing the functional activation of T cells. In summary, our study showed the usefulness of KHK-6 in the drug discovery for the HPK1-inhibiting immunotherapy.

Hispidin may represent a potential candidate for treating prostate cancer.

In vivo pharmacokinetic studies, compound 14g demonstrated heightened plasma exposure (AUC0-inf = 644 ng·h·mL-1), extended half-life (T1/2 = 9.98 h), and reduced plasma clearance (CL = 52.3 mL·min-1·kg-1) compared to the reference compound after a single intravenous dose of 2 mg/kg in rats. These results indicated that compound 14g emerged as a promising inhibitor of HPK1.

ONSMP can effectively reduce myocardial fibrosis in HF rats, and the mechanism may be related to the inhibition of the RAS/RAF/MEK/ERK signaling pathway.

P1/2, N=140, Recruiting, Deciphera Pharmaceuticals LLC | Not yet recruiting --> Recruiting

P1, N=32, Active, not recruiting, AstraZeneca | Completed --> Active, not recruiting | Trial completion date: Aug 2023 --> Aug 2026

P1, N=330, Recruiting, BeiGene | Trial completion date: Aug 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025

We identified molecular alterations and immune-related features that distinguish wtRET from mutRET MTC. While RET mutation drives MTC in the absence of other alterations, we showed that wtRET MTC frequently harbors MAPK pathway mutations. These findings may indicate a potential basis for MAPK-targeted therapy, possibly in combination with oncology immune-oncology agents for selected patients with wtRET MTC.

P1/2, N=170, Recruiting, Treadwell Therapeutics, Inc | Trial completion date: Jun 2024 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Nov 2024

KTBA decoction manipulates the expression of several key proteins in the p38MAPK/p65NF-κB/AQP4 signaling pathway, modulates gut microbiota and metabolites toward a more favorable profile, improves gut barrier function, delays cardiomyocyte hypertrophy and fibrosis,and improves cardiac function.

They are well described in solid malignancies, where many of the involved factors are used as prognostic molecular markers or targets for precision therapy. This narrative review focused, in the first part, on PGCs' survival/proliferation and differentiation and on the genetic and epigenetic factors involved in the pathogenesis of testicular germ cell tumors (TGCTs) and, in the second part, on the most recent investigations about the KIT-RAS pathway in TGCTs and in other cancers, highlighting the efforts that are being made to identify targetable markers for precision medicine approaches.

In summary, this study provides significant evidence that myricanol acts as a potent SIRT1 activator, targeting inflammatory signal pathways and oxidative stress to suppress excessive inflammatory responses. Our findings highlight the potential of myricanol as a novel therapeutic agent for the treatment of LPS-induced sepsis.