{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:47:20Z","timestamp":1792000040016,"version":"4.4.0"},"reference-count":58,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2016,8,17]],"date-time":"2016-08-17T00:00:00Z","timestamp":1471392000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005968","name":"Leukemia Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007780","name":"Indian Institute of Science","doi-asserted-by":"publisher","award":["DBT\/BF\/PR\/INS\/2011\u201012\/IISc"],"award-info":[{"award-number":["DBT\/BF\/PR\/INS\/2011\u201012\/IISc"]}],"id":[{"id":"10.13039\/100007780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research","doi-asserted-by":"publisher","award":["37(1579)\/13\/EMR\u2010II"],"award-info":[{"award-number":["37(1579)\/13\/EMR\u2010II"]}],"id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001427","name":"All India Council for Technical Education","doi-asserted-by":"publisher","award":["8023\/BOR\/RID\/RPS\u2010169\/2008\u201009"],"award-info":[{"award-number":["8023\/BOR\/RID\/RPS\u2010169\/2008\u201009"]}],"id":[{"id":"10.13039\/501100001427","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002183","name":"Department of Electronics and Information Technology, Ministry of Communications and Information Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002183","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:p>The antiapoptotic protein <jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>2 is overexpressed in several cancers and contributes to prolonged cell survival and chemoresistance, lending itself as an excellent target for cancer therapy. Here, we report the design, synthesis, and characterization of Disarib, a novel <jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>2 inhibitor. Disarib showed selective cytotoxicity in <jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>2 high cancer cell lines, and <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content> patient primary cells, as compared to <jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>2 low cell lines. <jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>2 knockdown in cells rendered remarkable resistance to Disarib, while sensitivity was regained upon its ectopic expression, establishing target specificity. <jats:italic>In silico<\/jats:italic>, biochemical and biophysical studies demonstrated strong affinity of Disarib to <jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>2, but not to other antiapoptotic <jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>2 family members viz., <jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">xL<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> BCL<\/jats:styled-content>2A1 etc. Interestingly, biophysical studies showed that <jats:styled-content style=\"fixed-case\">BH<\/jats:styled-content>1 domain deletion mutant demonstrated ~ 67\u2010fold reduction in <jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>2\u2010Disarib interaction, while it was only ~ 20\u2010fold in the case of <jats:styled-content style=\"fixed-case\">BH<\/jats:styled-content>3 deletion mutant, suggesting predominant involvement of the <jats:styled-content style=\"fixed-case\">BH<\/jats:styled-content>1 domain for Disarib binding. Thus, we report identification of a novel <jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>2 inhibitor with a unique mechanism of <jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>2 inhibition, as opposed to the well\u2010studied <jats:styled-content style=\"fixed-case\">BH<\/jats:styled-content>3 domain targeting.<\/jats:p>","DOI":"10.1111\/febs.13815","type":"journal-article","created":{"date-parts":[[2016,7,22]],"date-time":"2016-07-22T07:37:02Z","timestamp":1469173022000},"page":"3408-3437","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Identification of a novel <scp>BCL<\/scp>2\u2010specific inhibitor that binds predominantly to the <scp>BH<\/scp>1 domain"],"prefix":"10.1111","volume":"283","author":[{"given":"Divyaanka","family":"Iyer","sequence":"first","affiliation":[{"name":"Department of Biochemistry Indian Institute of Science Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supriya V.","family":"Vartak","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Indian Institute of Science Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archita","family":"Mishra","sequence":"additional","affiliation":[{"name":"Molecular Biophysics Unit Indian Institute of Science Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunaseelan","family":"Goldsmith","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics and Applied Biotechnology, Electronics City Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujeet","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry KLE University's College of Pharmacy Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mrinal","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Indian Institute of Science Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahesh","family":"Hegde","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Indian Institute of Science Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidya","family":"Gopalakrishnan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Indian Institute of Science Bangalore India"},{"name":"Institute of Bioinformatics and Applied Biotechnology, Electronics City Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Glenn","sequence":"additional","affiliation":[{"name":"Haematology Department of Molecular and Clinical Cancer Medicine University of Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahesh","family":"Velusamy","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics and Applied Biotechnology, Electronics City Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bibha","family":"Choudhary","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics and Applied Biotechnology, Electronics City Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagesh","family":"Kalakonda","sequence":"additional","affiliation":[{"name":"Haematology Department of Molecular and Clinical Cancer Medicine University of Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhas S.","family":"Karki","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry KLE University's College of Pharmacy Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avadhesha","family":"Surolia","sequence":"additional","affiliation":[{"name":"Molecular Biophysics Unit Indian Institute of Science Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sathees C.","family":"Raghavan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Indian Institute of Science Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,8,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2663"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1101-e255"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1133289"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.15.1899"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2007.12"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V81.11.3091.3091"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2003.08.009"},{"key":"e_1_2_9_9_1","first-page":"9","article-title":"Bcl\u20102 family proteins: regulators of apoptosis and chemoresistance in hematologic malignancies","volume":"34","author":"Reed JC","year":"1997","journal-title":"Semin Hematol"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2005.05.039"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.12.3929"},{"key":"e_1_2_9_12_1","first-page":"71","article-title":"Bcl\u20102\u2010related antisense therapy","volume":"29","author":"Gutierrez\u2010Puente Y","year":"2002","journal-title":"Semin Oncol"},{"key":"e_1_2_9_13_1","first-page":"1498","article-title":"Cell permeable Bcl\u20102 binding peptides: a chemical approach to apoptosis induction in tumor cells","volume":"60","author":"Wang JL","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi025605h"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2005.03.001"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-0945"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2006.08.027"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3048"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-3060"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401937"},{"key":"e_1_2_9_21_1","volume-title":"Targeted Cancer Therapy: The Role of BCL2 Inhibitors","author":"Iyer D","year":"2013"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2009.07.051"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2010.01.011"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2004.07.048"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.140350"},{"key":"e_1_2_9_26_1","first-page":"647","article-title":"Regulation of bcl\u20102, bcl\u2010XL and bax in the control of apoptosis by hematopoietic cytokines and dexamethasone","volume":"6","author":"Lotem J","year":"1995","journal-title":"Cell Growth Differ"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605224103"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.321"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00838a006"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0708800104"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V82.6.1820.1820"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1309\/491W-L1TN-UFQX-T61B"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.21867"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2008.09.002"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-09-113647"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1104778108"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2005.11.024"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2013.06.002"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.377"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-13-0609"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2014.1"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2011.02.064"},{"key":"e_1_2_9_44_1","first-page":"253","article-title":"Synthesis and cardiotonic activity of certain imidazo[2,1\u2010b]\u20101,3,4\u2010thiadiazole derivatives","volume":"136","author":"el\u2010Sherbeny MA","year":"1997","journal-title":"Boll Chim Farm"},{"key":"e_1_2_9_45_1","first-page":"777","article-title":"Preparation and reactivity of imidazo[2,1\u2010b]\u20101,3,4\u2010thiadiazoles","volume":"105","author":"Pentimalli L","year":"1975","journal-title":"Gazz Chim Ital"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21256"},{"key":"e_1_2_9_47_1","volume-title":"AMBER 14","author":"Case DA","year":"2014"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep06147"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.11.054"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2010.08.084"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-008-9212-6"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12457"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.004770"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pep.2008.04.005"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.307363"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2010.07.117"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2008.11.001"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2008.10.018"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0069103"}],"container-title":["The FEBS Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Ffebs.13815","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.13815","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T06:58:15Z","timestamp":1696316295000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1111\/febs.13815"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,17]]},"references-count":58,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2016,9]]}},"alternative-id":["10.1111\/febs.13815"],"URL":"https:\/\/doi.org\/10.1111\/febs.13815","archive":["Portico"],"relation":{},"ISSN":["1742-464X","1742-4658"],"issn-type":[{"value":"1742-464X","type":"print"},{"value":"1742-4658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,17]]},"assertion":[{"value":"2016-06-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-07-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-08-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}