ethynylcytidine (TAS-106) / Otsuka - LARVOL DELTA

Immunomodulation induced by the drug conjugates 5-Fluorodeoxyuridine-alendronate and 5- Fluorodeoxyuridine-C-ethynylcytidine in human epithelial ovarian carcinoma (CIMT 2024) - "Moreover, 5-FdU-ale treatment increases the density of CD8+ cytotoxic T cells in the tumor synergistically with immune checkpoint blockade (nivolumab). 5-FdU-ECyd additionally mediates a decrease in the concentration of immunosuppressive factors in the tissue. Based on our dataset in tissue explants, both drugs are excellent candidates for the treatment of EOC and definitely warrant further translational and clinical studies."

Immunomodulating • Immunology • Oncology • Ovarian Cancer • Solid Tumor

Chemoproteomic Approaches to Studying RNA Modification-Associated Proteins. (PubMed, Acc Chem Res) - "5-Ethynylcytidine-mediated cross-linking enabled the investigation of ALKBH1 substrates...Interestingly, we found that YTH-domain proteins YTHDF1/2 can bind to both mA and mA to mediate transcript destabilization. Furthermore, mA also inhibits stress granule proteins from binding to RNA.Taken together, we demonstrate the application of chemical probing strategies, together with proteomic and transcriptomic workflows, to reveal new insights into the biological roles of RNA modifications and their associated proteins."

Journal

Reactivity-dependent profiling of RNA 5-methylcytidine dioxygenases. (PubMed, Nat Commun) - "Here we present a chemoproteomic strategy to characterize RNA 5-methylcytidine (mC) dioxygenase enzymes in their native context based upon metabolic labeling and activity-based crosslinking with 5-ethynylcytidine (5-EC)...Finally, we show that fC at the wobble position of tRNA-Leu-CAA plays a role in decoding Leu codons under stress. Our work provides powerful chemical approaches for studying RNA mC dioxygenases and mapping oxidative mC modifications and reveals the existence of novel epitranscriptomic pathways for regulating RNA function."

Journal • TET2

The Metabolic and Non-Metabolic Roles of UCK2 in Tumor Progression. (PubMed, Front Oncol) - "By harnessing the catalytic activity of UCK2, several cytotoxic ribonucleoside analogs, such as TAS-106 and RX-3117, have been developed for UCK2-mediated cancer chemotherapy. These findings suggest that UCK2 may serve as a potential therapeutic target for cancer treatment. In this mini-review, we introduced the genomic localization and protein structure of UCK2, described the role of UCK2 in tumor development, discussed the application of UCK2 in anti-tumor treatment, and proposed concurrent targeting of the catalytic and non-catalytic roles of UCK2 as a potential therapeutic strategy for cancer treatment."

Journal • Review • Developmental Disorders • Hematological Malignancies • Lung Cancer • Oncology • Solid Tumor • EGFR

Nucleoside analogs as a radiosensitizer modulating DNA repair, cell cycle checkpoints, and apoptosis. (PubMed, Nucleosides Nucleotides Nucleic Acids) - "Certain types of nucleoside analogs have the inhibitory effects on RNA synthesis, but not DNA synthesis, with multiple functions in cell cycle modulation and apoptosis. In this review, the most up-to-date findings regarding radiosensitizing nucleoside analogs will be discussed, focusing especially on the mechanisms of action."

Journal • Oncology

Conformational Changes and Nuclear Entry of Porcine Circovirus Without Disassembly. (PubMed, J Virol) - "Genome labeling showed that the infectivity of the PCV2 virion was not affected by conjugation with deoxy-5-ethynylcytidine (EdC)...Antibody binding experiments with PCV2 showed that residues 186 to 192 were concealed in the early endosomes of epithelial PK-15 and monocytic 3D4/31 cells with or without chloroquine treatment and then exposed in PK-15 cytosol and the 3D4/31 nucleus...Here, we report the release of the PCV2 genome from assembled capsid, the intracellular trafficking of infectious PCV2 by alterations in the capsid conformation. Knowledge of PCV2 capsid stability and dynamics is essential to understanding its infectious cycle and lays the foundation for discovering powerful targets for therapeutic and prophylactic intervention."

Journal • Preclinical

Chemosensitivity of various peritoneal cancer cell lines to HIPEC and PIPAC: comparison of an experimental duplex drug to standard drug regimens in vitro. (PubMed, Invest New Drugs) - "A duplex drug, characterized by reversible linking of the antimetabolites 2'-deoxy-5-fluorouridine (5-FdU) and 3'-C-ethynylcytidine (ECyd), was compared to oxaliplatin or to cisplatin plus doxorubicin. Higher doses of the duplex drug will enhance growth inhibition, albeit at the cost of a severely reduced difference in chemosensitivity between tumor and normal cells. Our findings provide orientation for PIPAC-based personalized intraperitoneal chemotherapy."

Journal • Preclinical