Anticancer Fund

Inducing protein oligomerization holds therapeutic promise, yet identifying or rationally designing effective inducers remains challenging. In this study, we leverage nanopore technology to screen small molecules capable of modulating WD repeat domain 5 (WDR5) protein oligomerization and uncover a oligomerization mechanism which we term Catalytic Proximal Protein Oligomerization (CaPPO). Nanopore sensing enabled rapid identification of WZ-1, a selective WDR5 oligomerization inducer, from our in-house compound library. Biochemical and cryo-EM analyses reveal that WZ-1 binds the WBM site of WDR5 through its 2-aminothiazole moiety, reacts with Cys248 to form an intramolecular disulfide, and, through N-terminal tail-induced proximity of WDR5 molecules, triggers oligomerization via thio-disulfide exchange. Structure-activity relationship studies indicate that the disulfide motif within WZ-1 acts as a molecular scout initiating oligomerization. In cellular assays, WZ-1 exhibits potent anti-tumor activity by disrupting WDR5 interactions at both WIN and WBM sites, leading to transcriptional downregulation of target genes. Collectively, this work not only establishes a nanopore-based screening platform for identifying protein oligomerization inducers, but also validates CaPPO as a promising small-molecule design strategy for therapeutic development.

Apples and Korean green chili peppers are rich in phytochemicals and recognized for their diverse bioactive properties. Given the potential to enhance these beneficial compounds, this study investigated the effects of mineral supplementation during cultivation on the antioxidant and antiproliferative activities of extracts from both crops. Mineral-enriched cultivation significantly increased the total phenolic and flavonoid contents in both crops, which was accompanied by enhanced DPPH and ABTS radical scavenging activities. Moreover, the mineral-supplemented extracts of Korean green chili pepper activated the Nrf2 signaling pathway and upregulated downstream antioxidant enzymes, including heme oxygenase-1 (HO-1), γ-glutamylcysteine ligase (GCL), and glutathione peroxidase (GPx). Notably, the mineral-supplemented Korean green chili pepper extract significantly suppressed the proliferation of human colorectal cancer cells. These findings suggest that mineral supplementation during cultivation may improve the functional quality of apples and Korean green chili peppers, supporting their potential application in cancer prevention and complementary therapeutic strategies.

Pancreatic cancer (PC) remains one of the most challenging malignancies to treat. Current therapeutic options are unsatisfactory, and there is an urgent need for more effective and less toxic drugs to improve the dismal prognosis of PC. In recent years, drug repurposing (DR) has emerged as an attractive strategy to identify novel treatments for PC by leveraging existing drugs approved for other indications. Through the use of electronic medical records, Artificial Intelligence, study of metabolic pathways, signalling pathways, and many other approaches, it has become much easier in recent years to identify potential novel uses for old drugs. Although policy, funding and research attention in this area are steadily growing, major challenges to efficient and effective patient-centric DR in PC need to be addressed. These include but are not limited to regulatory, financial and funding barriers and the lack of coordination and collaboration among several sectors and stakeholders. To explore the opportunities and challenges associated with DR in PC, a one-day multi-stakeholder meeting was held on 14th of November 2023 in Brussels, Belgium as part of the REMEDi4ALL project. This meeting provided a platform for researchers, clinicians, industry representatives, funders, regulatory experts, and patient advocates to discuss and propose actions to optimize and accelerate DR in PC. Insights from this meeting support the potential of DR to enhance PC treatment options while highlighting the importance of systemic and supportive changes in the regulatory, policy and funding landscapes, interdisciplinary collaboration, data sharing, and patient involvement in driving therapeutic innovation. This summary highlights key outcomes and recommendations from the meeting in informing future efforts to advance DR initiatives in the context of PC.

To evaluate the biological activities of secondary metabolites obtained from Fusarium species. The secondary metabolites of Fusarium oxysporum showed a proliferative effect on MCF-7 cells. The secondary metabolites of Fusarium solani reduced the viability of the MCF-7 cell in 48 hours. The metabolites of both fungi showed significant antibacterial activity (p<0.0010) in E. coli strains at all concentrations. F.oxysporum and solani significantly inhibited S. aureus at all concentrations within 24h. F. oxysporum metabolites significantly reduced C. albicans at all concentrations within 24h. The secondary metabolites of Fusarium solani significantly (p<0.0001) reduced the viability of C. albicans at all concentrations. There are compounds in Fusarium solani with antitumor and antimicrobial properties.