|
Yuan H, Luo J, Weissleder
R, Cantley L, Josephson L.
Wortmannin-C20 conjugates generate wortmannin.
J Med Chem. 2006 Jan 26;49(2):740-7.
Center for Molecular Imaging Research, Massachusetts General
Hospital, Harvard Medical School, Charlestown, Massachusetts
02129, USA.
We report on C20-6-(N-methylamino)hexanoic conjugates of
wortmannin featuring a tertiary enamine attached to the C20 that
inhibit phosphoinositol-3-OH kinase (PI3K) by producing
wortmannin (Wm) through an intramolecular attack. The generation
of Wm by these conjugates permits the design of Wm based PI3K
inhibitors that need not fit into the ATP pocket of PI3K,
including Wm conjugates of BSA, IgG, or beads. Wm generating
WmC20-N(Me)-hexanoate conjugates offer an approach to the design
of targeted or slow release forms of Wm which may inhibit PI3K
in tissues more selectively than the parent Wm, a compound which
has desirable anti-inflammatory and anti-proliferative
activities but which also has a variety of toxic effects.
PMID: 16420059
|
