| Design and synthesis of Pictet-Spengler condensation products that exhibit oncogenic-RAS synthetic lethality and induce non-apoptotic cell death. | |
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MedLine Citation:
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PMID: 22832321 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A series of Pictet-Spengler condensation derivatives (tetrahydro-β-carbolines) was designed, synthesized and evaluated for lethality against a panel of seven cancer cell lines. Seven compounds (2a, 13, 20, 21, 27, 29 and 34) showed lethality in at least five cell lines. Among these, compound 27 showed a unique selectivity towards oncogenic-RAS expressing BJ-TERT/LT/ST/RAS(V12) tumor cells, compared to non-transformed BJ-TERT cells. Further investigation revealed that 27 induces cell death without activation of caspases. This represents a useful new probe of non-apoptotic cell death and oncogenic-RAS synthetic lethality. |
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Authors:
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Rachid Skouta; Miki Hayano; Kenichi Shimada; Brent R Stockwell |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-06-30 |
Journal Detail:
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Title: Bioorganic & medicinal chemistry letters Volume: 22 ISSN: 1464-3405 ISO Abbreviation: Bioorg. Med. Chem. Lett. Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-08-20 Completed Date: 2013-01-07 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 9107377 Medline TA: Bioorg Med Chem Lett Country: England |
Other Details:
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Languages: eng Pagination: 5707-13 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Biological Sciences, Columbia University, 550 West 120th Street, Northwest Corner Building, MC 4846, New York, NY 10027, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
/
chemical synthesis,
chemistry*,
pharmacology* Carbolines / chemical synthesis, chemistry*, pharmacology* Cell Death / drug effects Cell Line, Tumor Cell Survival / drug effects Drug Design Gene Expression Regulation, Neoplastic / drug effects Genes, ras / drug effects* Humans Neoplasms / drug therapy*, genetics |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA097061/CA/NCI NIH HHS; R01 CA161061/CA/NCI NIH HHS; R01 GM085081/GM/NIGMS NIH HHS; R01CA097061/CA/NCI NIH HHS; R01CA161061/CA/NCI NIH HHS; R01GM085081/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Carbolines |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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