Abstract:
:Hsp90 C-terminal inhibitors represent a novel and alternative chemotherapeutic approach for the treatment of cancer. Novobiocin was the first natural product identified as an Hsp90 C-terminal inhibitor; however, it manifests poor antiproliferative activity. In contrast to N-terminal inhibitors, novobiocin does not induce the pro-survival heat shock response. Structural investigations on novobiocin have elucidated some structure-activity relationships and several promising compounds. On the basis of structure-activity relationships and computational studies, a library of ring-constrained novobiocin analogues was designed, synthesized, and evaluated in antiproliferative assays. Results obtained from these studies provide insights into the Hsp90 C-terminal binding site, and new analogues that were developed manifest low micromolar to mid-nanomolar antiproliferative activity resulting from Hsp90 inhibition.
journal_name
ACS Med Chem Lettjournal_title
ACS medicinal chemistry lettersauthors
Garg G,Zhao H,Blagg BSdoi
10.1021/ml5004475subject
Has Abstractpub_date
2014-12-12 00:00:00pages
204-9issue
2issn
1948-5875journal_volume
6pub_type
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