ACS Med. Chem. Lett.All Publications/WebsiteOR SEARCH CITATIONS Recently ViewedYou have not visited any articles yet, Please visit some articles to see contents here. Received28 May 2013Accepted12 September 2013Published online17 September 2013Published inissue 14 November 2013https://doi.org/10.1021/ml400204nCopyright © 2013 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views2500Altmetric-Citations82LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.Get e-AlertsAbstractThe rhodacyanine, MKT-077, has antiproliferative activity against cancer cell lines through its ability to inhibit members of the heat shock protein 70 (Hsp70) family of molecular chaperones. However, MKT-077 is rapidly metabolized, which limits its use as either a chemical probe or potential therapeutic. We report the synthesis and characterization of MKT-077 analogues designed for greater stability. The most potent molecules, such as 30 (JG-98), were at least 3-fold more active than MKT-077 against the breast cancer cell lines MDA-MB-231 and MCF-7 (EC50 values of 0.4 ± 0.03 and 0.7 ± 0.2 μM, respectively). The analogues modestly destabilized the chaperone clients, Akt1 and Raf1, and induced apoptosis in these cells. Further, the microsomal half-life of JG-98 was improved at least 7-fold (t1/2 = 37 min) compared to MKT-077 (t1/2 5 min). Finally, NMR titration experiments suggested that these analogues bind an allosteric site that is known to accommodate MKT-077. These studies advance MKT-077 analogues as chemical probes for studying Hsp70s roles in cancer.KEYWORDS:Breast cancer mortalin Hsp90 proteostasis p53Supporting InformationARTICLE SECTIONSJump ToCompound characterization and methods for syntheses and biological studies. This material is available free of charge via the Internet at http://pubs.acs.org.ml400204n_si_001.pdf (268.52 kb) Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). 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Future Medicinal Chemistry 2014, 6 (13) , 1499-1513. https://doi.org/10.4155/fmc.14.100Export articles to MendeleyGet article recommendations from ACS based on references in your Mendeley library.Export articles to MendeleyGet article recommendations from ACS based on references in your Mendeley library. Please note: If you switch to a different device, you may be asked to login again with only your ACS ID. Please note: If you switch to a different device, you may be asked to login again with only your ACS ID. Please note: If you switch to a different device, you may be asked to login again with only your ACS ID. Please login with your ACS ID before connecting to your Mendeley account.Login with ACS ID This website uses cookies to improve your user experience. By continuing to use the site, you are accepting our use of cookies. Read the ACS privacy policy. CONTINUE