{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T14:33:20Z","timestamp":1775486000132,"version":"3.50.1"},"reference-count":34,"publisher":"Proceedings of the National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,4,24]]},"abstract":"<jats:p>\n            The telomerase enzyme is a potential therapeutic target in\n many human cancers. A series of potent inhibitors has been designed by\n computer modeling, which exploit the unique structural features of\n quadruplex DNA. These 3,6,9-trisubstituted acridine inhibitors are\n predicted to interact selectively with the human DNA quadruplex\n structure, as a means of specifically inhibiting the action of human\n telomerase in extending the length of single-stranded telomeric DNA.\n The anilino substituent at the 9-position of the acridine chromophore\n is predicted to lie in a third groove of the quadruplex. Calculated\n relative binding energies predict enhanced selectivity compared with\n earlier 3,6-disubstituted compounds, as a result of this substituent.\n The ranking order of energies is in accord with equilibrium binding\n constants for quadruplex measured by surface plasmon resonance\n techniques, which also show reduced duplex binding compared with the\n disubstituted compounds. The 3,6,9-trisubstututed acridines have potent\n            <jats:italic>in vitro<\/jats:italic>\n            inhibitory activity against human telomerase,\n with EC\n            <jats:sub>50<\/jats:sub>\n            values of up to 60 nM.\n          <\/jats:p>","DOI":"10.1073\/pnas.081560598","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:44:19Z","timestamp":1027694659000},"page":"4844-4849","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":419,"title":["Structure-based design of selective and potent G quadruplex-mediated telomerase inhibitors"],"prefix":"10.1073","volume":"98","author":[{"given":"Martin","family":"Read","sequence":"first","affiliation":[{"name":"Cancer Research Campaign Biomolecular Structure Unit, Chester\r Beatty Laboratories, The Institute of Cancer Research, London SW3 6JB,\r United Kingdom; Cancer Research Campaign Centre for\r Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey\r SM2 5NG, United Kingdom; and Department of Chemistry\r and Center for Biotechnology and Drug Design, Georgia State University,\r Atlanta, GA 30303-3083"}]},{"given":"R. John","family":"Harrison","sequence":"additional","affiliation":[{"name":"Cancer Research Campaign Biomolecular Structure Unit, Chester\r Beatty Laboratories, The Institute of Cancer Research, London SW3 6JB,\r United Kingdom; Cancer Research Campaign Centre for\r Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey\r SM2 5NG, United Kingdom; and Department of Chemistry\r and Center for Biotechnology and Drug Design, Georgia State University,\r Atlanta, GA 30303-3083"}]},{"given":"Barbara","family":"Romagnoli","sequence":"additional","affiliation":[{"name":"Cancer Research Campaign Biomolecular Structure Unit, Chester\r Beatty Laboratories, The Institute of Cancer Research, London SW3 6JB,\r United Kingdom; Cancer Research Campaign Centre for\r Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey\r SM2 5NG, United Kingdom; and Department of Chemistry\r and Center for Biotechnology and Drug Design, Georgia State University,\r Atlanta, GA 30303-3083"}]},{"given":"Farial A.","family":"Tanious","sequence":"additional","affiliation":[{"name":"Cancer Research Campaign Biomolecular Structure Unit, Chester\r Beatty Laboratories, The Institute of Cancer Research, London SW3 6JB,\r United Kingdom; Cancer Research Campaign Centre for\r Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey\r SM2 5NG, United Kingdom; and Department of Chemistry\r and Center for Biotechnology and Drug Design, Georgia State University,\r Atlanta, GA 30303-3083"}]},{"given":"Sharon H.","family":"Gowan","sequence":"additional","affiliation":[{"name":"Cancer Research Campaign Biomolecular Structure Unit, Chester\r Beatty Laboratories, The Institute of Cancer Research, London SW3 6JB,\r United Kingdom; Cancer Research Campaign Centre for\r Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey\r SM2 5NG, United Kingdom; and Department of Chemistry\r and Center for Biotechnology and Drug Design, Georgia State University,\r Atlanta, GA 30303-3083"}]},{"given":"Anthony P.","family":"Reszka","sequence":"additional","affiliation":[{"name":"Cancer Research Campaign Biomolecular Structure Unit, Chester\r Beatty Laboratories, The Institute of Cancer Research, London SW3 6JB,\r United Kingdom; Cancer Research Campaign Centre for\r Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey\r SM2 5NG, United Kingdom; and Department of Chemistry\r and Center for Biotechnology and Drug Design, Georgia State University,\r Atlanta, GA 30303-3083"}]},{"given":"W. David","family":"Wilson","sequence":"additional","affiliation":[{"name":"Cancer Research Campaign Biomolecular Structure Unit, Chester\r Beatty Laboratories, The Institute of Cancer Research, London SW3 6JB,\r United Kingdom; Cancer Research Campaign Centre for\r Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey\r SM2 5NG, United Kingdom; and Department of Chemistry\r and Center for Biotechnology and Drug Design, Georgia State University,\r Atlanta, GA 30303-3083"}]},{"given":"Lloyd R.","family":"Kelland","sequence":"additional","affiliation":[{"name":"Cancer Research Campaign Biomolecular Structure Unit, Chester\r Beatty Laboratories, The Institute of Cancer Research, London SW3 6JB,\r United Kingdom; Cancer Research Campaign Centre for\r Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey\r SM2 5NG, United Kingdom; and Department of Chemistry\r and Center for Biotechnology and Drug Design, Georgia State University,\r Atlanta, GA 30303-3083"}]},{"given":"Stephen","family":"Neidle","sequence":"additional","affiliation":[{"name":"Cancer Research Campaign Biomolecular Structure Unit, Chester\r Beatty Laboratories, The Institute of Cancer Research, London SW3 6JB,\r United Kingdom; Cancer Research Campaign Centre for\r Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey\r SM2 5NG, United Kingdom; and Department of Chemistry\r and Center for Biotechnology and Drug Design, Georgia State University,\r Atlanta, GA 30303-3083"}]}],"member":"341","published-online":{"date-parts":[[2001,4,17]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.34.1.331"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bb.23.060194.003415"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80760-6"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(99)80043-X"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/345458a0"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80538-3"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7605428"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/22780"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/13495"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.18.2388"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.25.14276"},{"key":"e_1_3_2_12_2","first-page":"341","volume":"14","author":"Neidle S","year":"1999","unstructured":"S Neidle, L R Kelland Anti-Cancer Drug Des 14, 341\u2013347 (1999).","journal-title":"Anti-Cancer Drug Des"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1997.1292"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/350718a0"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/3949"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm970199z"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7258(99)00065-0"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm990084q"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(99)00394-7"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm990287e"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi981330n"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja984153m"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/26.16.3724"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0969-2126(93)90015-9"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi001584k"},{"key":"e_1_3_2_26_2","volume-title":"amber","author":"Case D A","year":"2000","unstructured":"D A Case, D A Pearlman, J C Caldwell, T E Cheatham, W S Ross, C Simmerling, T Darden, K M Merz, R V Stanton, A Cheng, et al. amber (Univ. of California, San Francisco, , Version 6.0. 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