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dc.contributor.authorHanish, Bentley J
dc.contributor.authorHackney Price, Jennifer F
dc.contributor.authorKaneko, Ichiro
dc.contributor.authorMa, Ning
dc.contributor.authorvan der Vaart, Arjan
dc.contributor.authorWagner, Carl E
dc.contributor.authorJurutka, Peter W
dc.contributor.authorMarshall, Pamela A
dc.date.accessioned2018-07-25T00:04:51Z
dc.date.available2018-07-25T00:04:51Z
dc.date.issued2018-07-01
dc.identifier.citationHanish, B.J., Hackney Price, J.F., Kaneko, I., Ma, N., van der Vaart, A., Wagner, C.E., Jurutka, P.W., Marshall, P.A., A novel gene expression analytics-based approach to structure aided design of rexinoids for development as next-generation cancer therapeutics, Steroids (2018), doi: https://doi.org/10.1016/ j.steroids.2018.04.009en_US
dc.identifier.issn1878-5867
dc.identifier.pmid29704526
dc.identifier.doi10.1016/j.steroids.2018.04.009
dc.identifier.urihttp://hdl.handle.net/10150/628299
dc.description.abstractRexinoids are powerful ligands that bind to retinoid-X-receptors (RXRs) and show great promise as therapeutics for a wide range of diseases, including cancer. However, only one rexinoid, bexarotene (Targretin TM) has been successfully transitioned from the bench to the clinic and used to treat cutaneous T-cell lymphoma (CTCL). Our goal is to develop novel potent rexinoids with a less untoward side effect profile than bexarotene. To this end, we have synthesized a wide array of rexinoids with EC50 values and biological activity similar to bexarotene. In order to determine their suitability for additional downstream analysis, and to identify potential candidate analogs for clinical translation, we treated human CTCL cells in culture and employed microarray technology to assess gene expression profiles. We analyzed twelve rexinoids and found they could be stratified into three distinct categories based on their gene expression: similar to bexarotene, moderately different from bexarotene, and substantially different from bexarotene. Surprisingly, small changes in the structure of the bexarotene parent compound led to marked differences in gene expression profiles. Furthermore, specific analogs diverged markedly from our hypothesis in expression of genes expected to be important for therapeutic promise. However, promoter analysis of genes whose expression was analyzed indicates general regulatory trends along structural frameworks. Our results suggest that certain structural motifs, particularly the basic frameworks found in analog 4 and analog 9, represent important starting points to exploit in generating additional rexinoids for future study and therapeutic applications.en_US
dc.description.sponsorshipNational Institutes of Health National Cancer Institute [1 R15 CA139364-01A2]; Women and Philanthropy Grant; Genome Consortium for Active Teaching; NSF MRI [CHE-1531590]en_US
dc.language.isoenen_US
dc.publisherELSEVIER SCIENCE INCen_US
dc.rights© 2018 Elsevier Inc. All rights reserved.en_US
dc.subjectAnalyticsen_US
dc.subjectCanceren_US
dc.subjectGene expressionen_US
dc.subjectMicroarraysen_US
dc.subjectRXRen_US
dc.subjectRexinoidsen_US
dc.titleA novel gene expression analytics-based approach to structure aided design of rexinoids for development as next-generation cancer therapeuticsen_US
dc.typeArticleen_US
dc.contributor.departmentArizona State Universityen_US
dc.contributor.departmentUniv Arizona, Coll Med Phoenix, Dept Basic Med Sci, Phoenix, AZ USAen_US
dc.contributor.departmentUniv Arizona, Canc Ctr, Tucson, AZ USAen_US
dc.identifier.journalSteroidsen_US
dc.description.note12 month embargo; published online 26 April 2018en_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal accepted manuscripten_US
dc.source.journaltitleSteroids


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