{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:37:45Z","timestamp":1790764665181,"version":"4.1.0"},"reference-count":49,"publisher":"American Chemical Society (ACS)","issue":"23","license":[{"start":{"date-parts":[[2015,5,12]],"date-time":"2015-05-12T00:00:00Z","timestamp":1431388800000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["HHSN26120080001E"],"award-info":[{"award-number":["HHSN26120080001E"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,6,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Identifying small molecules that selectively bind to structured RNA motifs remains an important challenge in developing potent and specific therapeutics. Most strategies to find RNA-binding molecules have identified highly charged compounds or aminoglycosides that commonly have modest selectivity. Here we demonstrate a strategy to screen a large unbiased library of druglike small molecules in a microarray format against an RNA target. This approach has enabled the identification of a novel chemotype that selectively targets the HIV transactivation response (TAR) RNA hairpin in a manner not dependent on cationic charge. Thienopyridine 4 binds to and stabilizes the TAR hairpin with a Kd of 2.4 \u03bcM. Structure\u2013activity relationships demonstrate that this compound achieves activity through hydrophobic and aromatic substituents on a heterocyclic core, rather than cationic groups typically required. Selective 2\u2032-hydroxyl acylation analyzed by primer extension (SHAPE) analysis was performed on a 365-nucleotide sequence derived from the 5\u2032 untranslated region (UTR) of the HIV-1 genome to determine global structural changes in the presence of the molecule. Importantly, the interaction of compound 4 can be mapped to the TAR hairpin without broadly disrupting any other structured elements of the 5\u2032 UTR. Cell-based anti-HIV assays indicated that 4 inhibits HIV-induced cytopathicity in T lymphocytes with an EC50 of 28 \u03bcM, while cytotoxicity was not observed at concentrations approaching 1 mM.<\/jats:p>","DOI":"10.1021\/ja502754f","type":"journal-article","created":{"date-parts":[[2014,5,12]],"date-time":"2014-05-12T16:41:37Z","timestamp":1399912897000},"page":"8402-8410","source":"Crossref","is-referenced-by-count":138,"title":["Identification\nof Biologically Active, HIV TAR RNA-Binding\nSmall Molecules Using Small Molecule Microarrays"],"prefix":"10.1021","volume":"136","author":[{"given":"Joanna","family":"Sztuba-Solinska","sequence":"first","affiliation":[{"name":"National Cancer Institute , , , ,","place":["Frederick, Maryland, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpa R.","family":"Shenoy","sequence":"additional","affiliation":[{"name":"National Cancer Institute , , , ,","place":["Frederick, Maryland, United States"]},{"name":"Frederick National Laboratory , , , ,","place":["Frederick, Maryland, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Gareiss","sequence":"additional","affiliation":[{"name":"Yale University , , , ,","place":["New Haven, Connecticut, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren R. H.","family":"Krumpe","sequence":"additional","affiliation":[{"name":"National Cancer Institute , , , ,","place":["Frederick, Maryland, United States"]},{"name":"Frederick National Laboratory , , , ,","place":["Frederick, Maryland, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart F. 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