{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T11:14:36Z","timestamp":1788606876026,"version":"build-2803163510"},"reference-count":57,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,8,21]],"date-time":"2018-08-21T00:00:00Z","timestamp":1534809600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2018,8,21]],"date-time":"2018-08-21T00:00:00Z","timestamp":1534809600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["30970643"],"award-info":[{"award-number":["30970643"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31300674"],"award-info":[{"award-number":["31300674"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81173093"],"award-info":[{"award-number":["81173093"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81373311"],"award-info":[{"award-number":["81373311"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["J1103518"],"award-info":[{"award-number":["J1103518"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      The aim of this study was to obtain antitumour molecules targeting to activate\n                      <jats:styled-content style=\"fixed-case\">PKM<\/jats:styled-content>\n                      2 through adequate computational methods combined with biological activity experiments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The structure\u2010based virtual screening was utilized to screen effective activator targeting\n                      <jats:styled-content style=\"fixed-case\">PKM<\/jats:styled-content>\n                      2 from\n                      <jats:styled-content style=\"fixed-case\">ZINC<\/jats:styled-content>\n                      database. Molecular dynamics simulations were performed to evaluate the stability of the small molecule\u2010binding\n                      <jats:styled-content style=\"fixed-case\">PKM<\/jats:styled-content>\n                      2 complex systems. Then, cell survival experiments, glutaraldehyde crosslinking reaction, western blot, and\n                      <jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content>\n                      experiments were used to detect the effects of top hits on various cancer cells and the targeting specificity of\n                      <jats:styled-content style=\"fixed-case\">PKM<\/jats:styled-content>\n                      2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Two small molecules in 1,5\u20102H\u2010pyrrole\u2010dione were obtained after virtual screening. In vitro experiments demonstrated that\n                      <jats:styled-content style=\"fixed-case\">ZINC<\/jats:styled-content>\n                      08383544 specifically activated\n                      <jats:styled-content style=\"fixed-case\">PKM<\/jats:styled-content>\n                      2 and affected the expression of upstream and downstream genes of\n                      <jats:styled-content style=\"fixed-case\">PKM<\/jats:styled-content>\n                      2 during glycolysis, leading to the inhibition of tumour cell growth. These results indicate that\n                      <jats:styled-content style=\"fixed-case\">ZINC<\/jats:styled-content>\n                      08383544 conforms to the characteristics of\n                      <jats:styled-content style=\"fixed-case\">PKM<\/jats:styled-content>\n                      2 activator and is potential to be a novel\n                      <jats:styled-content style=\"fixed-case\">PKM<\/jats:styled-content>\n                      2 activator as antitumour drug.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      This work proves that\n                      <jats:styled-content style=\"fixed-case\">ZINC<\/jats:styled-content>\n                      08383544 promotes the formation of\n                      <jats:styled-content style=\"fixed-case\">PKM<\/jats:styled-content>\n                      2 tetramer, effectively blocks\n                      <jats:styled-content style=\"fixed-case\">PKM<\/jats:styled-content>\n                      2 nuclear translocation, and inhibits the growth of tumour, and\n                      <jats:styled-content style=\"fixed-case\">ZINC<\/jats:styled-content>\n                      08383544 may be a novel activator of\n                      <jats:styled-content style=\"fixed-case\">PKM<\/jats:styled-content>\n                      2. This work may provide a good choice of drug or molecular fragments for the antitumour strategy targeting\n                      <jats:styled-content style=\"fixed-case\">PKM<\/jats:styled-content>\n                      2. Screening of targeted drugs by combination of virtual screening and bioactivity experiments is a rapid method for drug discovery.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cpr.12509","type":"journal-article","created":{"date-parts":[[2018,8,22]],"date-time":"2018-08-22T12:05:23Z","timestamp":1534939523000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Computer\u2010aided identification of a novel pyruvate kinase M2 activator compound"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7324-9734","authenticated-orcid":false,"given":"Yuanyuan","family":"Li","sequence":"first","affiliation":[{"name":"College of Life Sciences and Key Laboratory of Bio\u2010resources and Eco\u2010environment Ministry of Education, State Key Laboratory of Biotherapy, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minyue","family":"Bao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlan","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Key Laboratory of Bio\u2010resources and Eco\u2010environment Ministry of Education, State Key Laboratory of Biotherapy, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Key Laboratory of Bio\u2010resources and Eco\u2010environment Ministry of Education, State Key Laboratory of Biotherapy, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Key Laboratory of Bio\u2010resources and Eco\u2010environment Ministry of Education, State Key Laboratory of Biotherapy, Sichuan University  Chengdu China"},{"name":"State Key Laboratory of Biotherapy\/Collaborative Innovation Centre for Biotherapy West China Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Key Laboratory of Bio\u2010resources and Eco\u2010environment Ministry of Education, State Key Laboratory of Biotherapy, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanfang","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Key Laboratory of Bio\u2010resources and Eco\u2010environment Ministry of Education, State Key Laboratory of Biotherapy, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinku","family":"Bao","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Key Laboratory of Bio\u2010resources and Eco\u2010environment Ministry of Education, State Key Laboratory of Biotherapy, Sichuan University  Chengdu China"},{"name":"State Key Laboratory of Oral Diseases National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University  Chengdu China"},{"name":"State Key Laboratory of Biotherapy\/Collaborative Innovation Centre for Biotherapy West China Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,8,21]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"324","article-title":"Understanding the Warburg effect: the metabolic requirements of cell proliferation","volume":"2009","author":"Vander Heiden MG","journal-title":"Science"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2015.12.001"},{"key":"e_1_2_8_4_1","first-page":"242513","article-title":"PKM2, a central point of regulation in cancer metabolism","volume":"2013","author":"Nicholas W","year":"2013","journal-title":"Int J Cell Biol"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2014.01.031"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2010.02.005"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.1975.tb00658.x"},{"key":"e_1_2_8_8_1","first-page":"1043","article-title":"Application of M2\u2010type pyruvate kinase in cancer diagnosis and therapy","volume":"20","author":"Cheng Z","year":"2013","journal-title":"Chinese J Cancer Prev Treat"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-2870"},{"key":"e_1_2_8_10_1","first-page":"377","article-title":"Tumor M2 pyruvate kinase \u2010 A tumor marker and indicator of inflammatory bowel disease activity","volume":"16","author":"Cichy W","year":"2009","journal-title":"Gastroenterologia Polska"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06734"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.2174\/1573406412666160307151535"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/1533034617749418"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2017.5761"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.26182"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2629"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.07.018"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.09.024"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.01.001"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10598"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0091606"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1060"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm901577g"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2012.08.054"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2013.12.028"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1549"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.1563609"},{"issue":"13","key":"e_1_2_8_28_1","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF chimera\u2014a visualization system for exploratory research and analysis","volume":"25","author":"Pettersen EF","year":"2010","journal-title":"J Comput Chem"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp961710n"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-2614(95)01082-K"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0282(2000)56:4<275::AID-BIP10024>3.0.CO;2-E"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1039\/c3mb70577c"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1039\/c2mb25110h"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2012.07.021"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2013.03.090"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/1758-2946-3-33"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts249"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-77"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci800072r"},{"key":"e_1_2_8_40_1","article-title":"A language and environment for statistical computing","author":"R Core Team","year":"2015","journal-title":"Computing"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt055"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.21123"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmgm.2005.12.005"},{"key":"e_1_2_8_44_1","volume-title":"AMBER 12","author":"Case DA","year":"2012"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-5-367"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20291"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1021\/ct700200b"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.470117"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/0263-7855(96)00018-5"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci500020m"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1088\/1749-4699\/5\/1\/015005"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.2144\/04375RV01"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci200227u"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1193494"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.4161\/jkst.20662"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-015-0132-x"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03197"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.14348\/molcells.2015.2314"}],"container-title":["Cell Proliferation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcpr.12509","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cpr.12509","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cpr.12509","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cpr.12509","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T12:54:24Z","timestamp":1778676864000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cpr.12509"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,21]]},"references-count":57,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["10.1111\/cpr.12509"],"URL":"https:\/\/doi.org\/10.1111\/cpr.12509","archive":["Portico"],"relation":{},"ISSN":["0960-7722","1365-2184"],"issn-type":[{"value":"0960-7722","type":"print"},{"value":"1365-2184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,21]]},"assertion":[{"value":"2018-03-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12509"}}