{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:51:03Z","timestamp":1790351463169,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,5,14]],"date-time":"2017-05-14T00:00:00Z","timestamp":1494720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology , Ministry of Science and Technology","doi-asserted-by":"publisher","award":["BT\/246\/NE\/TBP\/2011\/77"],"award-info":[{"award-number":["BT\/246\/NE\/TBP\/2011\/77"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology , Ministry of Science and Technology","doi-asserted-by":"publisher","award":["Sanction order No: BT\/PR14554\/INF\/22\/125\/2010 date"],"award-info":[{"award-number":["Sanction order No: BT\/PR14554\/INF\/22\/125\/2010 date"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:p>Chronic myeloid leukemia (<jats:styled-content style=\"fixed-case\">CML<\/jats:styled-content>) is a clonal myeloproliferative disorder of the hematopoietic stem cells, characterized at the molecular level by the <jats:italic>bcr\/abl<\/jats:italic> gene rearrangement. Even though targeting the fusion gene product Bcr\u2010Abl protein is a successful strategy, development of drug resistance and that of drug intolerance are currently the limitations for Bcr\u2010Abl\u2010targeted <jats:styled-content style=\"fixed-case\">CML<\/jats:styled-content> therapy. With an aim to develop natural Bcr\u2010Abl inhibitors, we performed virtual screening (<jats:styled-content style=\"fixed-case\">VS<\/jats:styled-content>) of <jats:styled-content style=\"fixed-case\">ZINC<\/jats:styled-content> natural compound database by docking with Abl kinase using Glide software. Two natural inhibitors <jats:styled-content style=\"fixed-case\">ZINC<\/jats:styled-content>08764498 (hit1) and <jats:styled-content style=\"fixed-case\">ZINC<\/jats:styled-content>12891610 (hit2) were selected by considering their high Glide docking score and critical interaction with the hinge region residue Met\u2010318 of Abl kinase. The reactivity of the two molecules was assessed computationally by density functional theory calculations. Further, the conformational transition, hydrogen bond interactions, and the binding energies were investigated during 10\u2010ns molecular dynamics simulation of the Abl\u2013hit complex. When tested in vitro, hit1 compared to hit2 showed selective inhibition of cell proliferation and induction of apoptosis in Bcr\u2010Abl\u2010positive K\u2010562 leukemia cells. In summary, our results demonstrate that <jats:styled-content style=\"fixed-case\">ZINC<\/jats:styled-content>08764498, a coumarin derivative identified through <jats:styled-content style=\"fixed-case\">VS<\/jats:styled-content>, is a potential natural inhibitor for the treatment of <jats:styled-content style=\"fixed-case\">CML<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/cbdd.12983","type":"journal-article","created":{"date-parts":[[2017,3,24]],"date-time":"2017-03-24T15:21:42Z","timestamp":1490368902000},"page":"596-608","source":"Crossref","is-referenced-by-count":20,"title":["Identification of natural inhibitors of Bcr\u2010Abl for the treatment of chronic myeloid leukemia"],"prefix":"10.1111","volume":"90","author":[{"given":"Phanikrishna","family":"Parcha","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology School of Life Sciences Pondicherry University  Puducherry India"},{"name":"DBT\u2010Interdisciplinary Program in Life Sciences School of Life Sciences Pondicherry University  Puducherry India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sailu","family":"Sarvagalla","sequence":"additional","affiliation":[{"name":"Centre for Bioinformatics School of Life Sciences Pondicherry University  Puducherry India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bindu","family":"Madhuri","sequence":"additional","affiliation":[{"name":"DBT\u2010Interdisciplinary Program in Life Sciences School of Life Sciences Pondicherry University  Puducherry India"},{"name":"Department of Biotechnology School of Life Sciences Pondicherry University  Puducherry India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sankar","family":"Pajaniradje","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology School of Life Sciences Pondicherry University  Puducherry India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinitha","family":"Baskaran","sequence":"additional","affiliation":[{"name":"Department of Medicine and Health Sciences SRM University  Kattankulathur, Chennai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohane Selvaraj","family":"Coumar","sequence":"additional","affiliation":[{"name":"DBT\u2010Interdisciplinary Program in Life Sciences School of Life Sciences Pondicherry University  Puducherry India"},{"name":"Centre for Bioinformatics School of Life Sciences Pondicherry University  Puducherry India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0441-0723","authenticated-orcid":false,"given":"Baskaran","family":"Rajasekaran","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology School of Life Sciences Pondicherry University  Puducherry India"},{"name":"DBT\u2010Interdisciplinary Program in Life Sciences School of Life Sciences Pondicherry University  Puducherry India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,5,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/243290a0"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31771"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.10.3343"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.7.1905b"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.17.6649"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"4947","DOI":"10.1182\/blood.V90.12.4947","volume":"90","author":"Carroll M.","year":"1997","journal-title":"Blood"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio799"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R112.438382"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2012.30"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1062538"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-12-326405"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-4187"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2005.05.011"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-8722-7-2"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2009.52"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402775"},{"issue":"2","key":"e_1_2_8_18_1","first-page":"11","volume":"6","author":"Thomas N. 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