MAPK14 (Mitogen-Activated Protein Kinase 14)

Although less potent than the nanomolar-range reference drug Epothilone B (IC50 < 0.1 μM), rugulosin A showed submicromolar-to-low micromolar efficacy with notable selectivity toward cancer cells, which is considered significant for an unoptimized natural product scaffold. Its antiproliferative activity against K562 cells (GI50 = 3.69 μM), benchmarked against Imatinib (GI50 = 0.373 μM), also falls within the active range of natural product leads...Molecular docking revealed strong binding energies (-10.1, -9.8, and -11.0 kcal/mol), along with a stable molecular dynamics simulations data. These findings highlight rugulosin A (3) as a promising anticancer lead that modulates major apoptosis signaling pathways.

Our findings elucidate multiple mechanisms by which CGs may exert anti-LSC activity, which could be crucial for the design of novel therapeutic strategies for AML. The proposed in silico framework is broadly applicable and may accelerate drug repurposing in AML and other cancers.

However, these predictions require confirmation through relevant in vitro and in vivo experimental studies to verify the precise mechanism, which is a limitation of the present work and a future scope. The online version contains supplementary material available at 10.1007/s40203-026-00604-9.

Our research re-evaluates the carcinogenic risks of plastic stabilizers and suggests that PSs may enhance breast cancer progression via targets such as MAPK14, PIM1, and TRDMT1. This study introduces a new approach for evaluating the safety of plastic additives and offers novel insights into the toxicological effects of PSs.

Potential therapeutic agents (e.g. capivasertib, lenalidomide) were predicted, and lenalidomide may represent a feasible initial treatment option for PTCL, with an objective response rate (ORR) of 40.0% and a maximum survival duration exceeding 50 months. NET-RGs play crucial roles in diagnosis, prognosis, and TME regulation, and lenalidomide, a putative TNF-targeting agent, may represent a feasible initial treatment option in PTCL.

The compounds, achieving IC50 values as low as 0.13 ± 0.02 μM, are over 290-fold more active in vitro than the clinical standard doxorubicin (IC50 = 38.17 ± 13.32 μM)...Additionally, these compounds reduce nuclear localization of myocardin-related transcription factor A (MRTF-A), a key driver of tumor resistance. This new study lays the groundwork for developing quinazoline-thiohydantoin-based drugs that can overcome multidrug-resistance mechanisms.

Importantly, YHD enhanced the sensitivity of OS cells to cisplatin, demonstrating a synergistic inhibitory effect in vitro and in an orthotopic OS mouse model. These findings suggest that YHD exerts its anti-osteosarcoma effects via reactive oxygen species-mediated mitochondrial disruption and pathway modulation, and may serve as a promising adjuvant to conventional chemotherapy.

Mechanistically, EHDPP binds to EGFR and inhibits its ubiquitination-mediated degradation, thereby stabilizing EGFR protein and partly activating the downstream PI3K-AKT signaling pathway, which ultimately promotes lung cancer cell proliferation and migration. This study is the first to elucidate the molecular mechanism underlying the pro-carcinogenic effects of EHDPP at the interaction level, providing potential molecular marker clues and mechanistic basis for EHDPP-related environmental risk assessment.

Collectively, our results provide a theoretical framework for understanding the complex mechanisms mediating ATBC-induced myocardial damage. They also offer crucial insights for developing preventive and therapeutic strategies targeting cardiac disorders potentially arising from exposure to ATBC-containing plastic products or environmental ATBC contamination.

Molecular docking suggested that DINP can potentially interact with key targets, especially MAPK14 and FAAH. Our findings suggest that DINP may promote GC development through interactions with core targets like MAPK14, highlighting its potential role as an environmental risk factor and a candidate biomarker.

This study offers a theoretical basis for the clinical use of Inula helenium in liver cancer treatment and encourages further investigation.

This study enhances our understanding of ARID1A regulatory mechanisms, highlighting its phosphorylation as a key driver of breast cancer biology. Future research should validate these kinase-substrate interactions and explore their transcriptional and chromatin-level impacts to develop precision therapies for ARID1A-dysregulated cancers.