Pharmacological rescue of mutant p53 conformation and function.

Science (New York, N.Y.) ·Vol. 286 ·No. 5449 ·1999-12-24 ·Pages 2507-10

Foster BA, Coffey HA, Morin MJ, Rastinejad F

Abstract

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.

MeSH Terms

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

Chemicals

Antineoplastic Agents Epitopes Pyrimidines Tumor Suppressor Protein p53 DNA CP 31398

Authors & Affiliations

4 authors, click to expand affiliations / ORCID

Foster B A

Department of Genomics, Targets, and Cancer Research, Pfizer Central Research, Eastern Point Road, Groton, CT 06340, USA.

Coffey H A

Morin M J

Rastinejad F

Article Info

Journal

Science (New York, N.Y.)

Abbr.

Science

ISSN

0036-8075

DOI

10.1126/science.286.5449.2507

Published

1999-12-24

Pages

2507-10

Language

English

Region

United States

NLM ID

0404511

Subset

Corrections

CommentIn

PMID: 10636794

External Links

PubMed source DOI: 10.1126/science.286.5449.2507 View journal details

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