RETRACTED: Prevention of chemotherapy-induced alopecia in rats by CDK inhibitors (Retracted Article. See vol 298, pg 2327, 2002)

被引:146
作者
Davis, ST
Benson, BG
Bramson, HN
Chapman, DE
Dickerson, SH
Dold, KM
Eberwein, DJ
Edelstein, M
Frye, SV
Gampe, RT
Griffin, RJ
Harris, PA
Hassell, AM
Holmes, WD
Hunter, RN
Knick, VB
Lackey, K
Lovejoy, B
Luzzio, MJ
Murray, D
Parker, P
Rocque, WJ
Shewchuk, L
Veal, JM
Walker, DH
Kuyper, LF
机构
[1] Glaxo Wellcome Inc, Res & Dev, Dept Canc Biol, Res Triangle Pk, NC 27709 USA
[2] Glaxo Wellcome Inc, Res & Dev, Dept Discovery Genet, Res Triangle Pk, NC 27709 USA
[3] Glaxo Wellcome Inc, Res & Dev, Dept Mol Biochem, Res Triangle Pk, NC 27709 USA
[4] Glaxo Wellcome Inc, Res & Dev, Dept Biomet Res Support, Res Triangle Pk, NC 27709 USA
[5] Glaxo Wellcome Inc, Res & Dev, Dept Med Chem, Res Triangle Pk, NC 27709 USA
[6] Glaxo Wellcome Inc, Res & Dev, Dept Struct Chem, Res Triangle Pk, NC 27709 USA
[7] Glaxo Wellcome Inc, Res & Dev, Dept Mol Sci, Res Triangle Pk, NC 27709 USA
关键词
D O I
10.1126/science.291.5501.134
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Most traditional cytotoxic anticancer agents ablate the rapidly dividing epithelium of the hair follicle and induce alopecia (hair Loss). Inhibition of cyclin-dependent kinase 2 (CDK2), a positive regulator of eukaryotic cell cycle progression, may represent a therapeutic strategy for prevention of chemotherapy-induced alopecia (CIA) by arresting the cell cycle and reducing the sensitivity of the epithelium to many cell cycle-active antitumor agents. Potent small-molecule inhibitors of CDK2 were developed using structure-based methods. Topical application of these compounds in a neonatal rat model of CIA reduced hair loss at the site of application in 33 to 50% of the animals. Thus, inhibition of CDK2 represents a potentially useful approach for the prevention of CIA in cancer patients.
引用
收藏
页码:134 / 137
页数:4
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