These findings establish EP as a novel Akt1-targeting agent that simultaneously blocks proliferative and metastatic pathways in prostate cancer. In conclusion, our results highlight the therapeutic potential of EP as a multitargeted, marine-derived compound for prostate cancer treatment.

Especially showing comparable stability to the reference molecule over 200 ns in MD simulations, the best top 2 hit compounds having binding affinity -10.7 kcal/mol for PCOS_ 133 (CID-164189) and -11.6 kcal/mol for PCOS3_42 (CID-158973) emerged as potential AKT1 inhibitors for cancer therapy in comparison to -11.6 kcal/mol and -14.7 kcal/mol binding affinity of Miransertib reference drug and IQO cocrystallized ligand of AKT1 protein PDB code 3O96. LEU-210, LEU-264, ASP-292, and TRP-80 are the important amino acid residues required for AKT1 inhibition. These results provide important new perspectives for the rational design and optimization of oxadiazole-based AKT1/PKB inhibitors, therefore laying a strong basis for experimental validation including further in-vitro and in vivo studies and PKB inhibitor development.

UA-Sol inhibited the AKT1/ERK1/2-GSK-3β-β-catenin axis to induce apoptosis, autophagy and anti-metastasis by targeting AKT1 and ERK1/2 inhibition. This dual-target drug combination strategy provides promising insights into the development of novel, safe, and efficient drugs for the treatment of CRC.

This study validated the anti-tumor efficacy of Lipo-HNK against NSCLC. Lipo-HNK reduced the infiltration of MDSCs and M2 macrophages by inhibiting the PI3K/Akt pathway and enhanced the therapeutic effects of ICIs. These findings provide evidence and new insights into Lipo-HNK as a promising anti-cancer drug for NSCLC treatment, highlighting its potential to overcome resistance to current ICI therapies.

Based on our findings, the liquid biopsy analysis using the PQS panel seems to be both feasible and accurate, demonstrating a strong sensitivity in detecting mutations. This exploratory analysis of the clinical outcome associated to the mutational status of patients highlights the potential of molecular analysis on liquid biopsy for disease monitoring, although further validation with a larger patient cohort is necessary to confirm these preliminary observations.

These findings, supported by molecular docking scores and MM-PBSA binding energies, advocate for their potential superior inhibitory capability against the AKT1 enzyme. Nevertheless, it is crucial to validate these computational predictions through in vitro and in vivo studies to thoroughly evaluate the therapeutic potential and viability of these compounds for AKT1-targeted breast cancer treatment.

Schisandrin C effectively suppressed the proliferation and viability of A549 cells. Its mechanism was related to the inhibition of the AKT1 signaling pathway.

Furthermore, the binding orientation of FeIII-L with Topoisomerase II was found to be the most stable, with a binding energy -8.25 kcal/mol. This stability was attributed to the presence of five hydrophobic π-interactions with His759, Guanin13, Cytosin8, and Ala465, and numerous ionic interactions, which were more favorable than those of doxorubicin and etoposide for new regimens of chemotherapeutic activities against skin cancer.

Additionally, AKT1 activity affected normal metabolism in HuH-7 cells and resulted in the accumulation of reactive oxygen species, which activated MOMP and further promoted apoptosis. Our results systematically elucidate the mechanism of luteolin in inhibiting the proliferation of liver cancer cells, mainly through cell cycle arrest and apoptosis via targeting AKT1 and SRC.

The pharmacological inhibition of AKT1 phosphorylation using MK2206 effectively counteracted the proliferative effects induced by PTOV1 overexpression. The ability of PTOV1 to enhance CRC cell proliferation via modulation of the AKT1 signaling pathway establishes it as a potential therapeutic target and a promising biomarker for prognostic stratification in CRC.

P1, N=110, Recruiting, Alterome Therapeutics, Inc. | Not yet recruiting --> Recruiting