2006•Journal of Medicinal ChemistryRequires access
Pegylated Wortmannin and 17-Hydroxywortmannin Conjugates as Phosphoinositide 3-Kinase Inhibitors Active in Human Tumor Xenograft Models
Tianmin Zhu, Jianxin Gu, Ker Yu, Judy Lucas, Ping Cai, Russ Tsao, Yumin Gong, Fangbiao Li, Inder Chaudhary, Parimal R. Desai, Mark Ruppen, Mahdi B. Fawzi, James J. Gibbons, Semiramis Ayral‐Kaloustian, Jerauld S. Skotnicki, Tarek S. Mansour, Arie Zask
Open publisher page 42 citations
Abstract
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.