HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)

All of these quantitative results prove that Mentha piperita has multi-target treatment potential against CRC. Although the computational forecast of the computational predictions suggests that TNF-α related signaling is a viable mechanistic pathway, they are still predictive and need to be further validated in wet-labs in order to confirm its clinical significance.

Finally, through virtual screening and Co-IP, we identified ivermectin as a potent inhibitor of the HSP90AB1-ITGBL1 interaction, and treatment with ivermectin dramatically inhibited OS progression in vivo. In conclusion, we uncover a novel mechanism that promotes OS progression and identify a new candidate drug for the treatment of OS.

Importantly, the synergistic effect induces immunogenic cell death (ICD), activating systemic antitumor immunity and suppressing metastasis. This work not only provides an integrated platform combining high drug loading, self-amplifying therapy, and immune activation but also establishes a foundation for developing natural product-based coordination nanomedicines.

Finally, a task-specific implementation of machine-learned classifiers trained on both apo and GDM-bound ensembles offers a residue-level mechanistic attribution to the overall recognition process, with conformational selection dominance in L4 and adjacent helices, induced-fit prevalence in L3 and the buried β-sheet and mixed contributions from α6-α7. This 'residual induced-fit' framework reconciles longstanding structural discrepancies and offers an intermediate-focused blueprint for targeting dynamic proteins via extensive sampling.

Collectively, these modulators demonstrate PPI druggability and provide chemical probes and lead scaffolds for therapeutic development in cancer, neurodegeneration, infectious disease, and immune disorders.

Crucially, the HSP90AB1 K265R mutation or pharmacological inhibition of ACOX1 (10,12-tricosadiynoic acid) or TXN (1-methyl-propyl 2-imidazolyl disulfide, PX-12) synergizes with cisplatin to suppress tumor growth in vivo by disrupting redox adaptation. These findings reveal that crotonylation is a hypoxia-sensitive rheostat for TXN-mediated redox control, suggesting that the ACOX1-HSP90AB1-TXN axis is a therapeutic vulnerability in therapy-resistant OSCC.

This integrative computational and mathematical approach elucidates the putative mechanistic interplay between drugs and phytochemicals, highlighting the potential of Artemisinin-Erlotinib (ART-ERL) combination therapy in overcoming drug resistance in NSCLC. The findings offer a promising framework for rational design of future combination strategies to improve clinical outcomes in lung cancer therapy.

Cellular experimental methods reported that GK suppresses A549 and LLC cell proliferation and metastasis. Our findings suggest that GK may exert its anti-NSCLC effect through the HSP90-AKT signaling pathway, providing a foundation for further study.

In both in vitro and in vivo experiments, this degrader displayed more potent activity than enzalutamide in inhibiting the proliferation and migration of CRPC cells. This study expands the application scope of the silicon-containing hydrophobic tag (SiHyT) strategy and provides an alternative design concept for the development of drugs targeting the degradation of AR/AR-V7 in the treatment of CRPC.

Subsequent SHAP analysis revealed SRC, HSP90AB1, HSP90AA1 and CDK1 as the key contributors to prognostic prediction, with each being highly expressed in BC and linked to poor clinical prognosis. Notably, among all chemicals screened, Disperse Yellow 3 exhibited the strongest binding affinity to these four key targets, demonstrating the strongest association with BC risk.

Discoidin I-like domain 3 is a novel gene with a potentially key role in BA-related liver fibrosis, possibly influencing the proliferation and apoptosis of cholangiocytes by regulating the PI3K-AKT signaling pathway, thereby participating in the occurrence and development of liver fibrosis. This study provides new insights into the molecular mechanisms and potential treatment strategies for BA.

Also underscored are the existence of commercially available drugs and patented compounds, as well as translational candidates featuring the 2-aminobenzothiazole pharmacophore. The paper emphasises the dual mechanistic targetability of 2-aminobenzothiazole derivatives as valuable lead compounds targeting both kinases and other targets in an innovative manner aimed at future development of targeted anti-cancer therapies.