Publication Date:
2001-01-06
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davis, S T -- Benson, B G -- Bramson, H N -- Chapman, D E -- Dickerson, S H -- Dold, K M -- Eberwein, D J -- Edelstein, M -- Frye, S V -- Gampe Jr, R T -- Griffin, R J -- Harris, P A -- Hassell, A M -- Holmes, W D -- Hunter, R N -- Knick, V B -- Lackey, K -- Lovejoy, B -- Luzzio, M J -- Murray, D -- Parker, P -- Rocque, W J -- Shewchuk, L -- Veal, J M -- Walker, D H -- Kuyper, L F -- New York, N.Y. -- Science. 2001 Jan 5;291(5501):134-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Biology, Glaxo Wellcome Research and Development, Research Triangle Park, NC 27709, USA. std41085@glaxowellcome.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11141566" target="_blank"〉PubMed〈/a〉
Keywords:
Alopecia/*chemically induced/*prevention & control
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Animals
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Animals, Newborn
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Antineoplastic Agents/*toxicity
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Antineoplastic Combined Chemotherapy Protocols/toxicity
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Apoptosis/drug effects
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*CDC2-CDC28 Kinases
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Cell Cycle/drug effects
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Cell Line
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinases/*antagonists & inhibitors/metabolism
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Cyclophosphamide/toxicity
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Cytoprotection/drug effects
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DNA/biosynthesis
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Doxorubicin/toxicity
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Drug Design
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Enzyme Inhibitors/chemical synthesis/chemistry/*pharmacology
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Epithelium/drug effects
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Etoposide/toxicity
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Hair Follicle/cytology/*drug effects
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Humans
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Indoles/chemical synthesis/chemistry/*pharmacology
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Mice
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Mice, SCID
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Phosphorylation
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Protein-Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
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Rats
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Retinoblastoma Protein/metabolism
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Scalp/transplantation
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Sulfonamides/chemical synthesis/chemistry/*pharmacology
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Transplantation, Heterologous
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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