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Design, Synthesis, and Characterization of Brequinar Conjugates as Probes to Study DHODH Inhibition
dc.contributor.authorMadak, Joseph T.
dc.contributor.authorCuthbertson, Christine R.
dc.contributor.authorChen, Wenmin
dc.contributor.authorShowalter, Hollis D.
dc.contributor.authorNeamati, Nouri
dc.date.accessioned2017-10-23T17:31:31Z
dc.date.available2018-12-03T15:34:05Zen
dc.date.issued2017-10-09
dc.identifier.citationMadak, Joseph T.; Cuthbertson, Christine R.; Chen, Wenmin; Showalter, Hollis D.; Neamati, Nouri (2017). "Design, Synthesis, and Characterization of Brequinar Conjugates as Probes to Study DHODH Inhibition." Chemistry – A European Journal 23(56): 13875-13878.
dc.identifier.issn0947-6539
dc.identifier.issn1521-3765
dc.identifier.urihttps://hdl.handle.net/2027.42/138895
dc.description.abstractBrequinar, a potent dihydroorotate dehydrogenase (DHODH) inhibitor, has been evaluated in multiple clinical trials as a potential treatment for cancer. To further understand brequinar‐based DHODH inhibition and DHODH′s therapeutic relevance in cancer, we have developed novel brequinar‐based probes. We disclose a 16‐step convergent synthesis of the first brequinar‐PROTAC and a four‐step approach towards the first mitochondrial‐directed brequinar probe. A PROTAC and mitochondria‐directed probe of brequinar both possess cytotoxicity that is superior to brequinar in a colony formation assay.Brequin′ news: A novel convergent synthesis of brequinar‐based probes to induce protein degradation (16 steps) and improve mitochondria accumulation (four steps) is disclosed.
dc.publisherWiley Periodicals, Inc.
dc.subject.otherPROTAC
dc.subject.othertriphenylphosphonium
dc.subject.otherDHODH
dc.subject.otherbrequinar
dc.titleDesign, Synthesis, and Characterization of Brequinar Conjugates as Probes to Study DHODH Inhibition
dc.typeArticleen_US
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelChemistry
dc.subject.hlbtoplevelScience
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/138895/1/chem201702999_am.pdf
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/138895/2/chem201702999-sup-0001-misc_information.pdf
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/138895/3/chem201702999.pdf
dc.identifier.doi10.1002/chem.201702999
dc.identifier.sourceChemistry – A European Journal
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