patupilone (EPO 906)

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.

P1, N=22, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027

Furthermore, therapeutic vulnerabilities were explored by integrating drug sensitivity prediction, AI-assisted cMAP screening, and molecular docking validation, which identified Epothilone B as a promising agent targeting HBEGF. Overall, this research shows that understanding the heterogeneity of CAFs with AI-enabled multi-omics modeling can reveal prognostic biomarkers and therapeutic targets for overcoming resistance, with the ultimate goal of improving precision oncology for HNSCC.

Drug sensitivity analysis indicated that bortezomib, docetaxel, and epothilone B were more effective in the high-risk group. The exosome-related risk model constructed in this study can effectively predict the prognosis of patients with STAD.

The present study developed a PRS using 101 machine learning combination algorithms, which could aid in risk stratification and prognosis for LUAD patients. The candidate drugs and target may provide new insights in the treatment of high PRS group patients.

The level of released LDH of HepG-2 cells was increased exponentially with the Epothilone concentration, ensuring their negative effect on the plasma membrane permeability. From the docking results, the binding energy of Epothilone B with the tubulin-β was -9.96 kcal/mol, that was lower than Taxol (-7.87 kcal/mol), ensuring the higher affinity of Epothilone B to bind with the β-tubulin protein.

Furthermore, drug sensitivity analysis indicated that high-risk patients were more sensitive to Thapsigargin, Docetaxel, AKT inhibitor VIII, Pyrimethamine, and Epothilone B, while showing higher resistance to drugs such as I-BET-762, PHA-665752, and Belinostat. This study provides a comprehensive analysis of NRGs in BC and establishes reliable ML-based diagnostic and prognostic models. The findings highlight the clinical relevance of NRGs in BC progression, immune regulation, and therapy response, offering potential targets for personalized treatment strategies.

This study successfully developed a prognostic model based on SRGs, effectively predicting the prognosis and drug response of KIRC patients. The model demonstrated significant predictive performance and potential clinical application value. Furthermore, the study highlighted the critical role of sialylation in KIRC, offering new insights into its underlying mechanisms in tumor biology. These findings could guide personalized treatment strategies for KIRC patients, emphasizing the importance of sialylation in cancer prognosis and therapy.

P2, N=349, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2026

The expression of fibronectin (FN) was significantly lower in the EpoB group, while the expression of Tau, neurofilament-M (NF-M), and growth-associated protein-43 (GAP-43) was significantly higher. In conclusion, EpoB treatment significantly increases the expression of Tau, NF-M, and GAP-43, suggesting a positive effect on axonal regeneration and repair.

P2, N=116, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026

Moreover, the abundant presence of ZHER2:342 on the surface effectively enhances the targeting capacity and tumor accumulation of the drug. Z-E ADCN can be internalized by cancer cells via HER2 receptor-mediated endocytosis followed by Epo B release in response to high levels of ROS, resulting in excellent anticancer efficacy in HER2-positive tumor models.