Kinisoquin (isoquercetin)

Rutin, trifolin (a kaempferol glycoside), and epigallocatechin exhibited the strongest binding (e.g. rutin: - 8.85 kcal/mol to VEGF-A), surpassing the reference inhibitor Pazopanib (- 3.56 kcal/mol) with multiple stabilizing interactions with these proteins, suggesting potential to interfere with tumor angiogenesis and cell survival pathways. Collectively, these findings provide a scientific basis for the traditional use of T. globiferus and support its fraction as promising sources of multi-targeted anticancer agents. The identification of bioactive compounds further establishes a foundation for bioassay-guided isolation, mechanistic validation, and future drug development.

P2, N=90, Recruiting, Memorial Sloan Kettering Cancer Center | Not yet recruiting --> Recruiting

ISOQ also potentiated standard cisplatin/gemcitabine chemotherapy. Notably, the combination of low-dose ISOQ plus ZAF achieved ≥ 80% inhibition of key tumor-associated markers at one-third the monotherapy dose and outperformed either agent alone. These findings support ISOQ and ZAF as promising agents for the treatment of cancer and CAT and establish thiol isomerase inhibition as a strategy to simultaneously target thrombosis, tumor progression, and immune escape.

The microbial-derived quercetins effectively induce apoptosis and inhibit HepG2 proliferation by inactivating the PI3K/Akt/mTOR signaling pathway. Quercetin is specifically predicted to directly inhibit PI3K and AKT proteins, underscoring the potential of these compounds as targeted anticancer candidates.

P2, N=90, Not yet recruiting, Memorial Sloan Kettering Cancer Center

<b></b> <i>Streptomyces griseoaurantiacus</i> HNF214 from beehives produces quercetin and isoquercetin, exhibiting both antibacterial and anticancer activities, likely via MAPK/ERK pathway inhibition. While promising, further safety and <i>in vivo</i> studies are crucial before therapeutic development.

Therefore, we investigated the interactions between the ligands quercetin (QUE), isoquercetin (ISO), catechin gallate (CG), and trichostatin A (TSA) with SIRT6, using computational methods from the perspective of molecular modeling through the Molecular Fractionation with Caps Conjugates (MFCC) technique and according to the calculation parameters of Density Functional Theory (DFT)...In addition, residues such as PRO62, MET136, MET157, and VAL115 stand out as key components of the protein active site. These findings offer strategic insights into the molecular mechanisms underlying the binding of the studied ligands to SIRT6, providing a deep understanding of their affinity and pharmacological potential.

Comparative docking with five reference drugs (Alpelisib, Buparlisib, Lapatinib, Gefitinib, and Afatinib) identified nine flavonoids; Sphaerobioside, Avicularin, Nicotiflorin, Myricetin, Quercitrin, Rutin, Isoquercetin, Didymin, and Robinin as promising candidates with favorable binding affinities and stable receptor interactions...Collectively, these findings highlight the multitarget inhibitory potential of selected flavonoids and demonstrate how integrated computational profiling can accelerate the discovery and optimization of natural product-based anticancer agents. The online version contains supplementary material available at 10.1007/s40203-025-00489-0.

P3, N=480, Recruiting, Quercis Pharma AG | Not yet recruiting --> Recruiting | N=340 --> 480 | Trial completion date: Dec 2026 --> Oct 2029 | Initiation date: Jun 2025 --> Oct 2025 | Trial primary completion date: Jul 2026 --> Oct 2027

Differentiated SH-SY5Y cell lines were treated with quercetin and selected derivatives against Methotrexate and 5-Fluorouracil (MF) toxicity, by subjecting to cytotoxicity assay, flow cytometry, and RT-PCR analysis.  Quercetin, Rutin, and Isoquercetin showed interactions necessary in the activation process of both proteins. Cytotoxicity and flow cytometric studies demonstrated that the phytochemicals shield the differentiated SH-SY5Y cells from MF toxicity. As determined by RT-PCR investigations, NAMPT and SIRT1 gene mRNA expression was higher in test drug-treated cells at quercetin (0.12, 0.6 µM), rutin, and isoquercetin (16, 80 µM) and lower in MF-treated cells.  The treatment of phytochemicals alleviated CICI by targeting NAMPT and SIRT1 proteins, which could lead to the identification of effective treatment strategies for the chemobrain.

P3, N=340, Not yet recruiting, Quercis Pharma AG

Histological improvements further support the potential of Vitis vinifera L. leaves as a natural lung protectant. Further pre-clinical and clinical investigations will be required to deliver a new drug with promising protection effect.