{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T17:57:31Z","timestamp":1763747851806},"reference-count":0,"publisher":"Bentham Science Publishers Ltd.","issue":"13","content-domain":{"domain":["eurekaselect.com"],"crossmark-restriction":true},"short-container-title":["CTMC"],"published-print":{"date-parts":[[2018,10,4]]},"abstract":"<jats:sec>\n<jats:title \/>\n<jats:p>Cancer has become one of the main leading causes of morbidity and mortality worldwide.\nOne of the critical drawbacks of current cancer therapeutics has been the lack of the target-selectivity, as\nthese drugs should have an effect exclusively on cancer cells while not perturbing healthy ones. In addition,\ntheir mechanism of action should be sufficiently fast to avoid the invasion of neighbouring healthy\ntissues by cancer cells. The use of conventional chemotherapeutic agents and other traditional therapies,\nsuch as surgery and radiotherapy, leads to off-target interactions with serious side effects. In this respect,\nrecently developed target-selective Antibody-Drug Conjugates (ADCs) are more effective than traditional\ntherapies, presumably due to their modular structures that combine many chemical properties simultaneously.\nIn particular, ADCs are made up of three different units: a highly selective Monoclonal\nantibody (Mab) which is developed against a tumour-associated antigen, the payload (cytotoxic agent),\nand the linker. The latter should be stable in circulation while allowing the release of the cytotoxic agent\nin target cells. The modular nature of these drugs provides a platform to manipulate and improve selectivity\nand the toxicity of these molecules independently from each other. This in turn leads to generation\nof second- and third-generation ADCs, which have been more effective than the previous ones in terms\nof either selectivity or toxicity or both. Development of ADCs with improved efficacy requires knowledge\nat the atomic level regarding the structure and dynamics of the molecule. As such, we reviewed all\nthe most recent computational methods used to attain all-atom description of the structure, energetics\nand dynamics of these systems. In particular, this includes homology modelling, molecular docking and\nrefinement, atomistic and coarse-grained molecular dynamics simulations, principal component and\ncross-correlation analysis. The full characterization of the structure-activity relationship devoted to\nADCs is critical for antibody-drug conjugate research and development.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/1568026618666180731165222","type":"journal-article","created":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T11:49:04Z","timestamp":1533124144000},"page":"1091-1109","update-policy":"http:\/\/dx.doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Computational Approaches in Antibody-drug Conjugate Optimization for Targeted Cancer Therapy"],"prefix":"10.2174","volume":"18","author":[{"given":"Rita","family":"Melo","sequence":"first","affiliation":[{"name":"Centro de Ciencias e Tecnologias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, CTN, Estrada Nacional 10 (km 139,7), 2695-066 Bobadela LRS, Portugal"}]},{"given":"Agostinho","family":"Lemos","sequence":"additional","affiliation":[{"name":"GIGA Cyclotron Research Centre In Vivo Imaging, University of Liege, 4000 Liege, Belgium"}]},{"given":"Antonio J.","family":"Preto","sequence":"additional","affiliation":[{"name":"CNC - Center for Neuroscience and Cell Biology; Rua Larga, FMUC, Polo I, 1\u00baandar, Universidade de Coimbra, 3004-517, Coimbra, Portugal"}]},{"given":"Jose G.","family":"Almeida","sequence":"additional","affiliation":[{"name":"CNC - Center for Neuroscience and Cell Biology; Rua Larga, FMUC, Polo I, 1\u00baandar, Universidade de Coimbra, 3004-517, Coimbra, Portugal"}]},{"given":"Joao D.G.","family":"Correia","sequence":"additional","affiliation":[{"name":"Centro de Ciencias e Tecnologias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, CTN, Estrada Nacional 10 (km 139,7), 2695-066 Bobadela LRS, Portugal"}]},{"given":"Ozge","family":"Sensoy","sequence":"additional","affiliation":[{"name":"Istanbul Medipol University, The School of Engineering and Natural Sciences, 34810, Istanbul, Turkey"}]},{"given":"Irina S.","family":"Moreira","sequence":"additional","affiliation":[{"name":"CNC - Center for Neuroscience and Cell Biology; Rua Larga, FMUC, Polo I, 1\u00baandar, Universidade de Coimbra, 3004-517, Coimbra, Portugal"}]}],"member":"965","container-title":["Current Topics in Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/eurekaselect.com\/article\/download\/164213","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.eurekaselect.com\/164213\/article","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eurekaselect.com\/article\/download\/164213","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,26]],"date-time":"2020-12-26T09:07:17Z","timestamp":1608973637000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.eurekaselect.com\/164213\/article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,4]]},"references-count":0,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2018,10,4]]}},"alternative-id":["LiveAll1"],"URL":"https:\/\/doi.org\/10.2174\/1568026618666180731165222","relation":{},"ISSN":["1568-0266"],"issn-type":[{"value":"1568-0266","type":"print"}],"subject":[],"published":{"date-parts":[[2018,10,4]]},"assertion":[{"value":"Peer Reviewed","order":0,"name":"review_status","label":"Review Status","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Single blind","order":1,"name":"review_process","label":"Review Process","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Checked with iThenticate","order":0,"name":"screening_status","label":"Screening Status","group":{"name":"plagiarism_screening","label":"Plagiarism Screening"}},{"value":"2018-05-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-08","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}