Publication Date:
2000-01-05
Description:
Compounds that stabilize the DNA binding domain of p53 in the active conformation were identified. These small synthetic molecules not only promoted the stability of wild-type p53 but also allowed mutant p53 to maintain an active conformation. A prototype compound caused the accumulation of conformationally active p53 in cells with mutant p53, enabling it to activate transcription and to slow tumor growth in mice. With further work aimed at improving potency, this class of compounds may be developed into anticancer drugs of broad utility.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Foster, B A -- Coffey, H A -- Morin, M J -- Rastinejad, F -- New York, N.Y. -- Science. 1999 Dec 24;286(5449):2507-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genomics, Targets, and Cancer Research, Pfizer Central Research, Eastern Point Road, Groton, CT 06340, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10617466" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antineoplastic Agents/chemistry/*pharmacology/therapeutic use
;
DNA/metabolism
;
Epitopes
;
Genes, p53
;
Humans
;
Mice
;
Mutation
;
Neoplasm Transplantation
;
Neoplasms, Experimental/*drug therapy/genetics/metabolism/pathology
;
Protein Conformation
;
Protein Folding
;
Protein Structure, Tertiary
;
Pyrimidines/chemistry/*pharmacology/therapeutic use
;
Temperature
;
Transcription, Genetic
;
Transfection
;
Transplantation, Heterologous
;
Tumor Cells, Cultured
;
Tumor Suppressor Protein p53/*chemistry/genetics/*metabolism
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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