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Zhu T, Gu J, Yu K, Lucas
J, Cai P, Tsao R, Gong Y, Li F, Chaudhary I, Desai P, Ruppen M,
Fawzi M, Gibbons J, Ayral-Kaloustian S, Skotnicki J, Mansour T,
Zask A.
Pegylated wortmannin and
17-hydroxywortmannin conjugates as phosphoinositide 3-kinase
inhibitors active in human tumor xenograft models.
J Med Chem. 2006 Feb
23;49(4):1373-8.
Preclinical Development, Wyeth Research, 401 North Middletown
Road, Pearl River, New York 10965, USA.
Phosphoinositide 3-kinase (PI3K) is an important target for
cancer chemotherapy due to the deregulation of its signaling
pathway in a wide spectrum of human tumors. Wortmannin and its
analogues are potent PI3K inhibitors whose therapeutic use has
been impeded by inherent defects such as instability and
toxicity. Pegylation of wortmannin and 17-hydroxywortmannin
gives rise to conjugates with improved properties, including a
higher therapeutic index. Pegylated 17-hydroxywortmannin (8,
PWT-458) has been selected for further development.
PMID: 16480272
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