This invention relates to compounds useful for visualizing cell senescence in vitro and in vivo, the preparation of said compounds and their use. In particular, this invention pertains to novel hexose and particularly galactose derivatives which are useful as senescence tracers in vitro and in vivo.
Cell senescence is the biological process by which cells exit the growth cycle. Cell senescence was first characterized in fibroblasts, which could only be subjected to a limited number of passages, before growth became permanently arrested. This phenomenon is named the Hayflick limit and serves to explain the physiological course of aging. It is accompanied by distinct change in metabolic pathways (Roninson, E.B., Tumor Cell Senescence in Cancer Treatment, Cancer Res., 2003, 63:2705-2715).
Senescent cells exhibit a senescence associated secretory phenotype, containing pro-inflammatory cytokines and growth factors. In certain instances, the removal of senescent tissues can convey great benefits to a patient. Senescence is recognized to play an important role in cancer treatment and therapy resistance. Treatment-associated senescence marks as stable clinical end point, and thus can be a measurement of chemotherapeutic success. The detection of senescence cells might also offer diagnostic opportunities for detecting pre-neoplastic lesions (Roninson, E.B., Tumor Cell Senescence in Cancer Treatment, Cancer Res., 2003, 63:2705-2715;and Campisi, J. and d'Adda di Fagagna, F., Cellular Senescence: when bad things happen to good cells, Nature Reviews Molecular Cell Biology, 2007, 8:729-740).
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