IRAK1 (Interleukin 1 Receptor Associated Kinase 1)

A34 potently inhibited IRAK1 with an IC50 value of 10.6 nM and demonstrated exceptional selectivity over 215 other kinases, notably including IRAK4. Furthermore, A34 demonstrated significant anti-HCC activity both in vivo and in vitro, making it a valuable chemical probe for IRAK1 and a potential lead candidate for the treatment of HCC.

To address this limitation, a multifunctional nanomedicine (PM-DPA/R848) was developed by loading the TLR7/8 agonist resiquimod (R848) into a nanocarrier composed of poly(L-methionine) (PM) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-poly(ethylene glycol)-alendronate (DSPE-PEG-ALN, DPA)...Moreover, DPA enhances intratumoral drug accumulation in vivo, and PM-DPA/R848 achieves a 77 % tumor suppression rate. Thus, PM-DPA/R848 acts as a precision nanoformulation that synergistically suppresses M2 macrophages and promotes M1 polarization, providing a promising strategy for osteosarcoma immunotherapy.

Nonetheless, CML therapy alleviated aforementioned disruptions via regulating redox balance, inflammatory and apoptotic profile of cardiac tissues. These findings suggest that CML could be employed in clinical research to validate these findings in humans.

Collectively, these findings emphasize the broad-spectrum activity of mollugin. This review provides a critical interpretation of the mechanistic pathways regulated by mollugin and its derivatives, emphasizing their pharmacological significance and exploring their potential for future translation as multitarget drug candidates.

IRAK1 influences the malignant biological behavior of GC cells by activating the PI3K/AKT/mTOR pathway and inducing the M2-like polarization of macrophages via the IL-8/JAK2/STAT3 pathway in TAMs. Our findings provide a novel diagnostic biomarker and a promising therapeutic strategy for GC.

It also reduced AML engraftment in leukemic mice. Our findings highlight the therapeutic potential of UR241-2 in targeting IL-1/IRAK1/4 signaling to eradicate LSCs and improve AML outcomes.

This study, integrating computational analysis, including network target and bioinformatics, with cellular experimental validation, reveals the inhibitory potential of PZH on hepatocellular carcinoma progression through the regulation of cell cycle-related pathways and biological processes. Notably, this study provides the first mechanistic insight into how PZH intervenes in the multi-step hepatocarcinogenesis, highlighting its potential role in preventing liver cancer development.

Importantly, PTPN22 knockout abrogated the anti-migratory effects of IRAK-M, confirming its essential role in this pathway. These findings establish the IRAK-M-PTPN22 axis as a critical suppressor of melanoma metastasis within the tumor microenvironment and highlight its potential as a therapeutic target to limit tumor dissemination and improve patient outcomes.

Notably, silencing RPS28 also disrupted both the oncogenic phenotype and downregulated MTA1, IRAK1, and TMSB10 expression. These findings reveal a complex interplay between FBL, rRNA Nm modifications, and RPS28 in shaping oncogenic protein pools and ribosomal composition in TNBC, offering promising insights into therapeutic approaches targeting this aggressive cancer subtype.

These integrated molecular effects were superior to those of free apigenin or blank EVs. Collectively, our findings highlight Apig-exo as a potent, multi-modal therapeutic platform capable of overcoming TNBC resistance via coordinated modulation of microRNA networks, apoptotic pathways, and epigenetic landscapes.

These findings establish SLC10A3 as a promising therapeutic target in HNC. Its consistent upregulation, association with poor prognosis, and potential interactions with key regulatory proteins highlight its relevance for future therapeutic strategies.

MiR-146a prevents AAA formation and progression by maintaining VSMC homeostasis in the proinflammatory microenvironment. Upregulation of miR-146a in the aortas shows great potential as a new therapeutic strategy to limit AAA expansion and progression.