Pharmacological Rescue of Mutant p53 Conformation and Function
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 conforma...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 1999-12, Vol.286 (5449), p.2507-2510 |
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| creator | Foster, Barbara A. Coffey, Heather A. Morin, Michael J. Rastinejad, Farzan |
| 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. |
| doi_str_mv | 10.1126/science.286.5449.2507 |
| format | Article |
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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.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.286.5449.2507</identifier><identifier>PMID: 10617466</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Society for the Advancement of Science</publisher><subject>Analysis ; Animals ; Antibodies ; Antineoplastic agents ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; Biological and medical sciences ; Cancer ; Cancer diagnosis ; Cell lines ; Cultured cells ; Deoxyribonucleic acid ; Diagnosis ; DNA ; DNA - metabolism ; Epitopes ; Gene mutation ; Gene mutations ; General aspects ; Genes ; Genes, p53 ; Genomics ; Heat ; Humans ; Ice ; Inductive reasoning ; Medical sciences ; Mice ; Mutation ; Neoplasm Transplantation ; Neoplasms, Experimental - drug therapy ; Neoplasms, Experimental - genetics ; Neoplasms, Experimental - metabolism ; Neoplasms, Experimental - pathology ; Pharmacology. Drug treatments ; Protein Conformation ; Protein Folding ; Protein Structure, Tertiary ; Pyrimidines - chemistry ; Pyrimidines - pharmacology ; Pyrimidines - therapeutic use ; Reporter genes ; Temperature ; Transcription, Genetic ; Transfection ; Transplantation, Heterologous ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53 - chemistry ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Protein p53 - metabolism ; Tumors ; Vehicles</subject><ispartof>Science (American Association for the Advancement of Science), 1999-12, Vol.286 (5449), p.2507-2510</ispartof><rights>Copyright 1999 American Association for the Advancement of Science</rights><rights>2000 INIST-CNRS</rights><rights>COPYRIGHT 1999 American Association for the Advancement of Science</rights><rights>COPYRIGHT 1999 American Association for the Advancement of Science</rights><rights>Copyright American Association for the Advancement of Science Dec 24, 1999</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c786t-9a3a0896b7f385b13859b99cbf44e20f540997f620c08d6ac0d84039cd6bcf4c3</citedby><cites>FETCH-LOGICAL-c786t-9a3a0896b7f385b13859b99cbf44e20f540997f620c08d6ac0d84039cd6bcf4c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2899883$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2899883$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,776,780,799,2870,2871,27903,27904,57995,58228</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1281893$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10617466$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Foster, Barbara A.</creatorcontrib><creatorcontrib>Coffey, Heather A.</creatorcontrib><creatorcontrib>Morin, Michael J.</creatorcontrib><creatorcontrib>Rastinejad, Farzan</creatorcontrib><title>Pharmacological Rescue of Mutant p53 Conformation and Function</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><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.</description><subject>Analysis</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Cancer</subject><subject>Cancer diagnosis</subject><subject>Cell lines</subject><subject>Cultured cells</subject><subject>Deoxyribonucleic acid</subject><subject>Diagnosis</subject><subject>DNA</subject><subject>DNA - metabolism</subject><subject>Epitopes</subject><subject>Gene mutation</subject><subject>Gene mutations</subject><subject>General aspects</subject><subject>Genes</subject><subject>Genes, p53</subject><subject>Genomics</subject><subject>Heat</subject><subject>Humans</subject><subject>Ice</subject><subject>Inductive reasoning</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mutation</subject><subject>Neoplasm Transplantation</subject><subject>Neoplasms, Experimental - drug therapy</subject><subject>Neoplasms, Experimental - genetics</subject><subject>Neoplasms, Experimental - metabolism</subject><subject>Neoplasms, Experimental - pathology</subject><subject>Pharmacology. 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| fulltext | fulltext |
| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 1999-12, Vol.286 (5449), p.2507-2510 |
| issn | 0036-8075 1095-9203 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_743720602 |
| source | American Association for the Advancement of Science; Jstor Complete Legacy; MEDLINE |
| subjects | Analysis Animals Antibodies Antineoplastic agents Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Biological and medical sciences Cancer Cancer diagnosis Cell lines Cultured cells Deoxyribonucleic acid Diagnosis DNA DNA - metabolism Epitopes Gene mutation Gene mutations General aspects Genes Genes, p53 Genomics Heat Humans Ice Inductive reasoning Medical sciences Mice Mutation Neoplasm Transplantation Neoplasms, Experimental - drug therapy Neoplasms, Experimental - genetics Neoplasms, Experimental - metabolism Neoplasms, Experimental - pathology Pharmacology. Drug treatments Protein Conformation Protein Folding Protein Structure, Tertiary Pyrimidines - chemistry Pyrimidines - pharmacology Pyrimidines - therapeutic use Reporter genes Temperature Transcription, Genetic Transfection Transplantation, Heterologous Tumor Cells, Cultured Tumor Suppressor Protein p53 - chemistry Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism Tumors Vehicles |
| title | Pharmacological Rescue of Mutant p53 Conformation and Function |
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