Click chemistry enables preclinical evaluation of targeted epigenetic therapies

Nom de la revue
Dean S. Tyler, Johanna Vappiani, Tatiana Cañeque, Enid Y. N. Lam, Aoife Ward, Omer Gilan, Yih-Chih Chan, Antje Hienzsch, Anna Rutkowska, Thilo Werner, Anne J. Wagner, Dave Lugo, Richard Gregory, Cesar Ramirez Molina, Neil Garton, Christopher R. Wellaway, Susan Jackson, Laura MacPherson, Margarida Figueiredo, Sabine Stolzenburg, Charles C. Bell, Colin House, Sarah-Jane Dawson, Edwin D. Hawkins, Gerard Drewes, Rab K. Prinjha, Raphaël Rodriguez, Paola Grandi, Mark A. Dawson

Are better drugs just a click away?

Drugs that show promise in preclinical models often fail in the clinic, in part because
of limited information on drug localization within cells and across tissues. In a
proof-of-concept study, Tyler
et al.
applied click chemistry methods to
study the localization of bromodomain inhibitors. These are cancer drugs that alter
chromatin structure and gene expression. Clickable derivatives of the drugs localized
within chromatin and showed that the drugs exhibit distinct modes of binding at
responsive and unresponsive genes. In a mouse leukemia model, the click-probes revealed
that the drugs accumulate to different extents in the spleen and bone marrow, which are
two tissue sources of leukemic cells.

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