{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T13:08:44Z","timestamp":1783602524197,"version":"3.55.0"},"reference-count":27,"publisher":"American Chemical Society (ACS)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ACS Med. Chem. Lett."],"published-print":{"date-parts":[[2010,4,8]]},"DOI":"10.1021\/ml900028r","type":"journal-article","created":{"date-parts":[[2010,1,19]],"date-time":"2010-01-19T10:10:17Z","timestamp":1263895817000},"page":"39-43","source":"Crossref","is-referenced-by-count":341,"title":["Discovery of GSK2126458, a Highly Potent Inhibitor of PI3K and the Mammalian Target of Rapamycin"],"prefix":"10.1021","volume":"1","author":[{"given":"Steven D.","family":"Knight","sequence":"first","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas D.","family":"Adams","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joelle L.","family":"Burgess","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amita M.","family":"Chaudhari","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Darcy","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla A.","family":"Donatelli","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan I.","family":"Luengo","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken A.","family":"Newlander","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia A.","family":"Parrish","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lance H.","family":"Ridgers","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha A.","family":"Sarpong","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley J.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn S.","family":"Van Aller","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D.","family":"Carson","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melody A.","family":"Diamond","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia A.","family":"Elkins","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M.","family":"Gardiner","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Garver","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth A.","family":"Gilbert","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard R.","family":"Gontarek","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey R.","family":"Jackson","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin L.","family":"Kershner","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lusong","family":"Luo","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaushik","family":"Raha","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian S.","family":"Sherk","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiu-Mei","family":"Sung","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sutton","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Tummino","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald J.","family":"Wegrzyn","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt R.","family":"Auger","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dashyant","family":"Dhanak","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2010,1,19]]},"reference":[{"key":"ref1\/cit1","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/nrg1879","volume":"7","author":"Engelman J. A.","year":"2006","journal-title":"Nat. Rev. Genet."},{"key":"ref2\/cit2","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/0092-8674(89)90182-7","volume":"57","author":"Auger K. R.","year":"1989","journal-title":"Cell"},{"key":"ref3\/cit3","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/nrc1819","volume":"6","author":"Cully M.","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"ref4\/cit4","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1126\/science.1096502","volume":"304","author":"Samuels Y.","year":"2004","journal-title":"Science"},{"key":"ref5\/cit5","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1073\/pnas.0408864102","volume":"102","author":"Kang S.","year":"2005","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref6\/cit6","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1073\/pnas.0510857103","volume":"103","author":"Bader A. G.","year":"2006","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref7\/cit7","doi-asserted-by":"crossref","first-page":"18443","DOI":"10.1073\/pnas.0508988102","volume":"102","author":"Zhao J. J.","year":"2005","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref8\/cit8","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.tibs.2007.05.005","volume":"32","author":"Vogt P. K.","year":"2007","journal-title":"Trends Biochem. Sci."},{"key":"ref9\/cit9","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/sj.bjc.6602970","volume":"94","author":"Karakas B.","year":"2006","journal-title":"Br. J. Cancer"},{"key":"ref10\/cit10","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1146\/annurev.cellbio.17.1.615","volume":"17","author":"Katso R.","year":"2001","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref11\/cit11","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.coph.2008.08.004","volume":"8","author":"Yap T. A.","year":"2008","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref12\/cit12","doi-asserted-by":"crossref","first-page":"2839","DOI":"10.2174\/092986709788803222","volume":"16","author":"Kong D.","year":"2009","journal-title":"Curr. Med. Chem."},{"key":"ref13\/cit13","doi-asserted-by":"crossref","unstructured":"Auger, K. R.; Luo, L.; Knight, S. D.; Van Aller, G.; Tummino, P. J.; Copeland, R. A.; Diamond, M.; Sutton, D.; Lu, H.; Oleykowski, K.; Sudakin, V.; Dhanak, D.; Jackson, J. R. GSK1059615: A Novel Inhibitor of Phosphoinositide 3-Kinase for the Treatment of Cancer. EORTC-NCI-AACR International Conference on Molecular Targets and Cancer, Geneva Palexpo, Geneva, Switzerland, October, 2008.","DOI":"10.1016\/S1359-6349(08)72153-0"},{"key":"ref14\/cit14","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/46319","volume":"402","author":"Walker E. H.","year":"1999","journal-title":"Nature"},{"key":"ref15\/cit15","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/S1097-2765(05)00089-4","volume":"6","author":"Walker E. H.","year":"2000","journal-title":"Mol. Cell"},{"key":"ref16\/cit16","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.cell.2006.03.035","volume":"125","author":"Knight Z. A.","year":"2006","journal-title":"Cell"},{"key":"ref17\/cit17","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1126\/science.1150799","volume":"318","author":"Huang C.-H.","year":"2007","journal-title":"Science"},{"key":"ref18\/cit18","unstructured":"Adams, N. D.; Burgess, J. L.; Darcy, M. G.; Donatelli, C. A.; Knight, S. D.; Newlander, K. A.; Ridgers, L.; Sarpong, M.; Schmidt, S. J. Preparation of quinoline derivatives as PI3 kinase inhibitors. WO2008144463, November 27, 2008."},{"key":"ref19\/cit19","unstructured":"Adams, N. D.; Chaudhari, A. M.; Donatelli, C. A.; Knight, S. D.; Newlander, K. A.; Parrish, C. A.; Ridgers, L.; Sarpong, M. A. Preparation of quinoline derivatives as PI3 kinase inhibitors. WO2008144464, November 27, 2008."},{"key":"ref20\/cit20","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/S0003-2697(02)00607-3","volume":"313","author":"Gray A.","year":"2003","journal-title":"Anal. Biochem."},{"key":"ref21\/cit21","volume-title":"The PyMOL Molecular Graphics System","author":"DeLano W. L.","year":"2002"},{"key":"ref22\/cit22","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1158\/1535-7163.MCT-08-0017","volume":"7","author":"Maira S.-M.","year":"2008","journal-title":"Mol. Cancer Ther."},{"key":"ref23\/cit23","doi-asserted-by":"crossref","first-page":"5522","DOI":"10.1021\/jm800295d","volume":"51","author":"Folkes A. J.","year":"2008","journal-title":"J. Med. Chem."},{"key":"ref25\/cit25","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1038\/nature04869","volume":"441","author":"Shaw R. J.","year":"2006","journal-title":"Nature"},{"key":"ref26\/cit26","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1126\/science.1106148","volume":"307","author":"Sarbassov D. D.","year":"2005","journal-title":"Science"},{"key":"ref27\/cit27","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1006\/excr.1999.4701","volume":"253","author":"Vanhaesebroeck B.","year":"1999","journal-title":"Exp. Cell Res."},{"key":"ref28\/cit28","unstructured":"For additional in vivo characterization, see the following: Hardwicke, M. A.; Lu, H.; Luo, L.; Diamond, M.; Sung, C.M.; Carson, J. D.; Plant, R.; Gardiner, C.; Wang, J.; Oleykowski, K.; Gontarek, R. R.; Van Aller, G.; Gilbert, S.; Sutton, D.; Tummino, P. J.; Wooster, R.; Knight, S. D.; Jackson, J. R.; Dhanak, D.; Auger, K. R. Biological Characterization of GSK2126458, A Novel and Potent Inhibitor of Phosphoinositide 3-Kinase and the Mammalian Target of Rapamycin (mTOR). EORTC-NCI-AACR International Conference on Molecular Targets and Cancer, Boston, MA, November, 2009."}],"container-title":["ACS Medicinal Chemistry Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/ml900028r","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T02:02:17Z","timestamp":1679536937000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/doi\/10.1021\/ml900028r"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,1,19]]},"references-count":27,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,4,8]]}},"alternative-id":["10.1021\/ml900028r"],"URL":"https:\/\/doi.org\/10.1021\/ml900028r","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1789957.1319055","asserted-by":"object"}]},"ISSN":["1948-5875","1948-5875"],"issn-type":[{"value":"1948-5875","type":"print"},{"value":"1948-5875","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,1,19]]}}}