Bioorganic & medicinal chemistry

Targeting the gatekeeper residue in phosphoinositide 3-kinases

PJ Alaimo, ZA Knight, KM Shokat

文献索引：Alaimo, Peter J.; Knight, Zachary A.; Shokat, Kevan M. Bioorganic and Medicinal Chemistry, 2005 , vol. 13, # 8 p. 2825 - 2836

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被引用次数: 60

摘要

A single residue in the ATP binding pocket of protein kinases—termed the gatekeeper—has been shown to control sensitivity to a wide range of small molecule inhibitors (Chem. Biol. 2004, 11, 691; Chem. Biol. 1999, 6, 671). Kinases that possess a small side chain at this position (Thr, Ala, or Gly) are readily targeted by structurally diverse classes of inhibitors, whereas kinases that possess a larger residue at this position are broadly resistant. ...