| Establishment of substituent effects in the DNA binding subunit of CBI analogues of the duocarmycins and CC-1065. | |
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MedLine Citation:
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PMID: 12901927 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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An extensive series of CBI analogues of the duocarmycins and CC-1065 exploring substituent effects within the first indole DNA binding subunit is detailed. In general, substitution at the indole C5 position led to cytotoxic potency enhancements that can be >/=1000-fold providing simplified analogues containing a single DNA binding subunit that are more potent (IC(50)=2-3 pM) than CBI-TMI, duocarmycin SA, or CC-1065. |
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Authors:
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Jay P Parrish; David B Kastrinsky; Frederic Stauffer; Michael P Hedrick; Inkyu Hwang; Dale L Boger |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Bioorganic & medicinal chemistry Volume: 11 ISSN: 0968-0896 ISO Abbreviation: Bioorg. Med. Chem. Publication Date: 2003 Aug |
Date Detail:
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Created Date: 2003-08-06 Completed Date: 2004-04-08 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 9413298 Medline TA: Bioorg Med Chem Country: England |
Other Details:
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Languages: eng Pagination: 3815-38 Citation Subset: IM |
Affiliation:
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Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550North Torrey Pines Road, La Jolla, CA 92037, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alkylation Amides / chemical synthesis, chemistry DNA / drug effects, metabolism* Indoles / chemical synthesis, chemistry*, metabolism, toxicity* Kinetics Models, Molecular Pyrroles / chemical synthesis, chemistry*, metabolism Pyrrolidinones / chemical synthesis, chemistry*, metabolism Sulfones / chemical synthesis, chemistry |
| Grant Support | |
ID/Acronym/Agency:
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CA41986/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amides; 0/Indoles; 0/Pyrroles; 0/Pyrrolidinones; 0/Sulfones; 118292-34-5/duocarmycin A; 130288-24-3/duocarmycin SA; 69866-21-3/CC 1065; 9007-49-2/DNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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