| Quinazoline Sulfonamides as Dual Binders of the Proteins B-Cell Lymphoma 2 and B-Cell Lymphoma Extra Large with Potent Proapoptotic Cell-Based Activity. | |
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MedLine Citation:
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PMID: 21366295 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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ABT-737 and ABT-263 are potent inhibitors of the BH3 antiapoptotic proteins, Bcl-x(L) and Bcl-2. This class of putative anticancer agents invariantly contains an acylsulfonamide core. We have designed and synthesized a series of novel quinazoline-based inhibitors of Bcl-2 and Bcl-x(L) that contain a heterocyclic alternative to the acylsulfonamide. These compounds exhibit submicromolar, mechanism-based activity in human small-cell lung carcinoma cell lines in the presence of 10% human serum. This comprises the first successful demonstration of a quinazoline sulfonamide core serving as an effective benzoylsulfonamide bioisostere. Additionally, these novel quinazolines comprise only the second known class of Bcl-2 family protein inhibitors to induce mechanism-based cell death. |
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Authors:
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Brad E Sleebs; Peter E Czabotar; Wayne J Fairbrother; W Douglas Fairlie; John A Flygare; David C S Huang; Wilhelmus J A Kersten; Michael F T Koehler; Guillaume Lessene; Kym Lowes; John P Parisot; Brian J Smith; Morey L Smith; Andrew J Souers; Ian P Street; Hong Yang; Jonathan B Baell |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-2 |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: - ISSN: 1520-4804 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-3-3 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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