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dc.contributor.authorHall, Jessica Ann
dc.contributor.authorSeedarala, Sahithi
dc.contributor.authorZhao, Huiping
dc.contributor.authorGarg, Gaurav
dc.contributor.authorGhosh, Suman
dc.contributor.authorBlagg, Brian S. J.
dc.identifier.citationHall, J. A., Seedarala, S., Zhao, H., Garg, G., Ghosh, S., & Blagg, B. S. J. (2016). Novobiocin Analogs That Inhibit the MAPK Pathway. Journal of Medicinal Chemistry, 59(3), 925–933.
dc.descriptionThis document is the Accepted Manuscript version of a Published Work that appeared in final form in the Journal of Medicinal Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see
dc.description.abstractHeat shock protein 90 (Hsp90) inhibition by modulation of the N-or C-terminal binding site has become an attractive strategy for the development of anti-cancer chemotherapeutics. The first Hsp90 C-terminus inhibitor, novobiocin, manifested a relatively high IC50 value of ~700 μM. Therefore, investigation of the novobiocin scaffold has led to analogs with improved antiproliferative activity (nanomolar concentrations) against several cancer cell lines. During these studies, novobiocin analogs that do not inhibit Hsp90 were identified; however, these analogs demonstrated potent anti-proliferative activity. Compound 2, a novobiocin analog, was identified as a MAPK pathway signaling disruptor that lacked Hsp90 inhibitory activity. In addition, structural modifications of compound 2 were identified that segregated Hsp90 inhibition from MAPK signaling disruption. These studies indicate that compound 2 represents a novel scaffold for disruption of MAPK pathway signaling and may serve as a useful structure for the generation of new anti-cancer agents.en_US
dc.publisherAmerican Chemical Societyen_US
dc.subjectClient proteinen_US
dc.subjectMAPK signaling pathwayen_US
dc.subjectFeed-back mechanismen_US
dc.subjectStructure-activity relationshipen_US
dc.titleNovobiocin Analogs That Inhibit the MAPK Pathwayen_US
kusw.kuauthorHall, Jessica A.
kusw.kuauthorSeedarala, Sahithi
kusw.kuauthorZhao, Huiping
kusw.kuauthorGarg, Gaurav
kusw.kuauthorGhosh, Suman
kusw.kuauthorBlagg, Brian S. J.
kusw.kudepartmentMedicinal Chemistryen_US
kusw.oanotesPer SHERPA/RoMEO 6/6/2017: Author's Pre-print: grey tick subject to Restrictions below, author can archive pre-print (ie pre-refereeing) Restrictions:

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On author's personal website, pre-print servers, institutional website, institutional repositories or subject repositories Non-Commercial Must be accompanied by set statement (see policy) Must link to publisher version Publisher's version/PDF cannot be used
kusw.oaversionScholarly/refereed, author accepted manuscripten_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US

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