Click chemistry enables preclinical evaluation of targeted epigenetic therapies

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.

Science
, this issue p.
1397