PDPK1 (3-Phosphoinositide dependent protein kinase 1)

Moreover, the inhibitory effects of miR-374b-5p on OS progression were partially reversed by PDPK1 overexpression both in vitro and in vivo. MiR-374b-5p was lowly expressed in OS, and its upregulation inhibited the progression of OS by directly targeting PDPK1 to affect the activity of the AKT pathway.

Based on these observations, we further conducted functional verification on Lcpik3r3b and discovered that its recombinant protein could significantly inhibit the proliferation of E. coli. These results would provide valuable insights into the roles of the PI3K family in mediating immune and stress responses in large yellow croaker, and laid a foundation for future investigations into their molecular mechanisms as well as potential applications in aquaculture disease management.

In a mouse xenograft model, acetylcholine administration accelerated tumor growth in animals bearing control pancreatic cancer cells but not in those implanted with nAChR-α7-knockdown cells. Collectively, our findings reveal a novel mechanism of acetylcholine-induced enhancement of HIF-1α expression involving PDPK1/YAP signaling and highlight the utility of HIF-1α as a therapeutic target in acetylcholine-potentiated pancreatic cancer.

In vitro 2D cytotoxicity assays demonstrated potent antiproliferative activity, with IC₅₀ values of 3.93 ± 0.47 μM in A549 and 4.88 ± 1.42 μM in non-small cell lung cancer (NSCLC) cells, while showing reduced cytotoxicity in normal fibroblasts (MRC-5; IC₅₀ = 10.48 ± 1.83 μM) compared with osimertinib. Molecular docking and in silico conformational analyses demonstrated strong binding affinity of compound 3 to the VEGFR-2 kinase domain, stabilizing critical active-site residues and supporting a structure-based mechanism of action. Collectively, these findings validate VEGFR-2 as a therapeutic target and highlight compound 3 as a promising scaffold for structure-based drug development against non-small cell lung cancer.

We comprehensively analyze the structure-activity relationships (SAR), biological activities, and mechanisms of action of these modulators, while also addressing persistent challenges and therapeutic opportunities in the field. This work offers rational design frameworks and strategic insights for developing novel PDK1-targeted therapeutics with optimized efficacy and safety profiles.

Cell-cycle analyses confirm enhanced DNA damage response and G2/M arrest when combined with olaparib. These findings uncover a novel mechanism for BX-912, establish HES1 inhibition as a therapeutic strategy in HGSC, demonstrate proteomics' power to reveal hidden drug activities, and propose sequential cell-cycle targeting to improve treatment efficacy.

The findings suggest PDK1 as a critical regulator of glycolytic metabolism and a potential therapeutic target in osteosarcoma. Targeting PDK1 could provide a novel therapeutic strategy for treating osteosarcoma and possibly other cancers.

Functional assays demonstrated that KP372-1, a dual 3-phosphoinositide-dependent protein kinase-1 (PDK1)/protein kinase B (AKT)/Fms-like tyrosine kinase (Flt) pathway inhibitor, markedly suppressed GBM cell proliferation, migration, and invasion, while promoting apoptosis. These findings establish TEK as a molecular driver of GBM progression and underscore its potential as a druggable macromolecular target for therapeutic strategies aimed at modulating the vascular-immune axis.

The analysis of ADMET properties indicated that all inhibitor compounds exhibit favorable pharmacological characteristics, including adherence to Lipinski's Rule of Five (Ro5) as well as the Ghose, Veber, and Egan rules. Additionally, the physicochemical properties demonstrate that all synthesized compounds are capable of human intestinal absorption and have the ability to penetrate the blood-brain barrier (BBB).

Furthermore, LAS impairs ATP production from glycolysis, ultimately resulting in energy depletion and cancer cell death. These findings highlight the potential of LAS as an autophagy-targeting therapeutic agent for breast cancer treatment and provide new insights into its anti-cancer mechanisms.

PDPK1 may be a downstream target of miR-361-5p. Low expression of BMSCs-derived exosomal miR-361-5p may reverse the effect of bortezomib on U266 cells by regulating the PDPK1/PI3K/AKT/mTOR axis.ConclusionLow expression of BMSCs-derived exosomal miR-361-5p may overcome bortezomib resistance in MM by regulating PDPK1/PI3K/AKT/mTOR axis.

USP22 knockdown in a xenograft assay also inhibited tumor growth via regulating PDK1. Taken together, these results indicate that USP22 regulated by YY1 plays a promotional role in NB progression by mediating the deubiquitination of PDK1.