Small-molecule inhibition of Wee1 kinase by MK-1775 selectively sensitizes p53-deficient tumor cells to DNA-damaging agents

Hirai, Hiroshi; Iwasawa, Yoshikazu; Okada, Megumu; Arai, Tsuyoshi; Nishibata, Toshihide; Kobayashi, Makiko; Kimura, Toshifumi; Kaneko, Naoki; Ohtani, Junko; Yamanaka, Kazunori; Itadani, Hiraku; Takahashi-Suzuki, Ikuko; Fukasawa, Kazuhiro; Oki, Hiroko; Nambu, Tadahiro; Jiang, Jian; Sakai, Takumi; Arakawa, Hiroharu; Sakamoto, Toshihiro; Sagara, Takeshi; Yoshizumi, Takashi; Mizuarai, Shinji; Kotani, Hidehito

doi:10.1158/1535-7163.mct-09-0463

Small-molecule inhibition of Wee1 kinase by MK-1775 selectively sensitizes p53-deficient tumor cells to DNA-damaging agents

Wee1 is a tyrosine kinase that phosphorylates and inactivates CDC2 and is involved in G2 checkpoint signaling. Because p53 is a key regulator in the G1 checkpoint, p53-deficient tumors rely only on the G2 checkpoint after DNA damage. Hence, such tumors are selectively sensitized to DNA-damaging a…