{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T12:55:38Z","timestamp":1767963338938,"version":"3.49.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Human breast cancer resistance protein (BCRP) is an ATP-binding cassette (ABC) efflux transporter that confers multidrug resistance in cancers and also plays an important role in the absorption, distribution and elimination of drugs. Prediction as to if drugs or new molecular entities are BCRP substrates should afford a cost-effective means that can help evaluate the pharmacokinetic properties, efficacy, and safety of these drugs or drug candidates. At present, limited studies have been done to develop <jats:italic>in silico<\/jats:italic> prediction models for BCRP substrates.<\/jats:p>\n            <jats:p>In this study, we developed support vector machine (SVM) models to predict wild-type BCRP substrates based on a total of 263 known BCRP substrates and non-substrates collected from literature. The final SVM model was integrated to a free web server.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We showed that the final SVM model had an overall prediction accuracy of ~73% for an independent external validation data set of 40 compounds. The prediction accuracy for wild-type BCRP substrates was ~76%, which is higher than that for non-substrates. The free web server (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/bcrp.althotas.com\" ext-link-type=\"uri\">http:\/\/bcrp.althotas.com<\/jats:ext-link>) allows the users to predict whether a query compound is a wild-type BCRP substrate and calculate its physicochemical properties such as molecular weight, logP value, and polarizability.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>We have developed an SVM prediction model for wild-type BCRP substrates based on a relatively large number of known wild-type BCRP substrates and non-substrates. This model may prove valuable for screening substrates and non-substrates of BCRP, a clinically important ABC efflux drug transporter.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2105-14-130","type":"journal-article","created":{"date-parts":[[2013,4,15]],"date-time":"2013-04-15T18:00:45Z","timestamp":1366048845000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Predicting substrates of the human breast cancer resistance protein using a support vector machine method"],"prefix":"10.1186","volume":"14","author":[{"given":"Eszter","family":"Hazai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Istvan","family":"Hazai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Ragueneau-Majlessi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie P","family":"Chung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zsolt","family":"Bikadi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingcheng","family":"Mao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,4,15]]},"reference":[{"issue":"7","key":"5843_CR1","doi-asserted-by":"publisher","first-page":"603","DOI":"10.2174\/138920010792927325","volume":"11","author":"Z Ni","year":"2010","unstructured":"Ni Z, Bikadi Z, Rosenberg MF, Mao Q: Structure and function of the human breast cancer resistance protein (BCRP\/ABCG2). Curr Drug Metab. 2010, 11 (7): 603-617. 10.2174\/138920010792927325.","journal-title":"Curr Drug Metab"},{"issue":"8","key":"5843_CR2","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1016\/j.bcp.2012.01.002","volume":"83","author":"K Natarajan","year":"2012","unstructured":"Natarajan K, Xie Y, Baer MR, Ross DD: Role of breast cancer resistance protein (BCRP\/ABCG2) in cancer drug resistance. Biochem Pharmacol. 2012, 83 (8): 1084-1103. 10.1016\/j.bcp.2012.01.002.","journal-title":"Biochem Pharmacol"},{"issue":"8","key":"5843_CR3","first-page":"3458","volume":"61","author":"M Maliepaard","year":"2001","unstructured":"Maliepaard M, Scheffer GL, Faneyte IF, van Gastelen MA, Pijnenborg AC, Schinkel AH, van De Vijver MJ, Scheper RJ, Schellens JH: Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues. Cancer Res. 2001, 61 (8): 3458-3464.","journal-title":"Cancer Res"},{"issue":"3","key":"5843_CR4","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1038\/nrd3028","volume":"9","author":"KM Giacomini","year":"2010","unstructured":"Giacomini KM, Huang SM, Tweedie DJ, Benet LZ, Brouwer KL, Chu X, Dahlin A, Evers R, Fischer V, Hillgren KM: Membrane transporters in drug development. Nat Rev Drug Discov. 2010, 9 (3): 215-236. 10.1038\/nrd3028.","journal-title":"Nat Rev Drug Discov"},{"issue":"4","key":"5843_CR5","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1016\/j.str.2010.01.017","volume":"18","author":"MF Rosenberg","year":"2010","unstructured":"Rosenberg MF, Bikadi Z, Chan J, Liu X, Ni Z, Cai X, Ford RC, Mao Q: The human breast cancer resistance protein (BCRP\/ABCG2) shows conformational changes with mitoxantrone. Structure. 2010, 18 (4): 482-493. 10.1016\/j.str.2010.01.017.","journal-title":"Structure"},{"issue":"3","key":"5843_CR6","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1208\/s12248-009-9132-1","volume":"11","author":"YA Gandhi","year":"2009","unstructured":"Gandhi YA, Morris ME: Structure-activity relationships and quantitative structure-activity relationships for breast cancer resistance protein (ABCG2). AAPS J. 2009, 11 (3): 541-552. 10.1208\/s12248-009-9132-1.","journal-title":"AAPS J"},{"issue":"6","key":"5843_CR7","doi-asserted-by":"publisher","first-page":"505","DOI":"10.2174\/138955712800493825","volume":"12","author":"T Ishikawa","year":"2012","unstructured":"Ishikawa T, Hirano H, Saito H, Sano K, Ikegami Y, Yamaotsu N, Hirono S: Quantitative structure-activity relationship (QSAR) analysis to predict drug-drug interactions of ABC transporter ABCG2. Mini Rev Med Chem. 2012, 12 (6): 505-514. 10.2174\/138955712800493825.","journal-title":"Mini Rev Med Chem"},{"issue":"1","key":"5843_CR8","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.addr.2008.10.004","volume":"61","author":"E Nicolle","year":"2009","unstructured":"Nicolle E, Boumendjel A, Macalou S, Genoux E, Ahmed-Belkacem A, Carrupt PA, Di Pietro A: QSAR analysis and molecular modeling of ABCG2-specific inhibitors. Adv Drug Deliv Rev. 2009, 61 (1): 34-46. 10.1016\/j.addr.2008.10.004.","journal-title":"Adv Drug Deliv Rev"},{"issue":"4","key":"5843_CR9","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/j.bcp.2005.05.017","volume":"70","author":"S Zhang","year":"2005","unstructured":"Zhang S, Yang X, Coburn RA, Morris ME: Structure activity relationships and quantitative structure activity relationships for the flavonoid-mediated inhibition of breast cancer resistance protein. Biochem Pharmacol. 2005, 70 (4): 627-639. 10.1016\/j.bcp.2005.05.017.","journal-title":"Biochem Pharmacol"},{"issue":"1","key":"5843_CR10","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S0960-894X(00)00588-6","volume":"11","author":"A van Loevezijn","year":"2001","unstructured":"van Loevezijn A, Allen JD, Schinkel AH, Koomen GJ: Inhibition of BCRP-mediated drug efflux by fumitremorgin-type indolyl diketopiperazines. Bioorg Med Chem Lett. 2001, 11 (1): 29-32. 10.1016\/S0960-894X(00)00588-6.","journal-title":"Bioorg Med Chem Lett"},{"issue":"1","key":"5843_CR11","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1124\/jpet.107.124768","volume":"323","author":"P Matsson","year":"2007","unstructured":"Matsson P, Englund G, Ahlin G, Bergstrom CA, Norinder U, Artursson P: A global drug inhibition pattern for the human ATP-binding cassette transporter breast cancer resistance protein (ABCG2). J Pharmacol Exp Ther. 2007, 323 (1): 19-30. 10.1124\/jpet.107.124768.","journal-title":"J Pharmacol Exp Ther"},{"issue":"12","key":"5843_CR12","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1002\/cmdc.200700160","volume":"2","author":"J Cramer","year":"2007","unstructured":"Cramer J, Kopp S, Bates SE, Chiba P, Ecker GF: Multispecificity of drug transporters: probing inhibitor selectivity for the human drug efflux transporters ABCB1 and ABCG2. ChemMedChem. 2007, 2 (12): 1783-1788. 10.1002\/cmdc.200700160.","journal-title":"ChemMedChem"},{"issue":"17","key":"5843_CR13","doi-asserted-by":"publisher","first-page":"8224","DOI":"10.1016\/j.bmc.2008.07.034","volume":"16","author":"A Pick","year":"2008","unstructured":"Pick A, Muller H, Wiese M: Structure-activity relationships of new inhibitors of breast cancer resistance protein (ABCG2). Bioorg Med Chem. 2008, 16 (17): 8224-8236. 10.1016\/j.bmc.2008.07.034.","journal-title":"Bioorg Med Chem"},{"issue":"11","key":"5843_CR14","doi-asserted-by":"publisher","first-page":"4852","DOI":"10.1158\/0008-5472.CAN-04-1817","volume":"65","author":"A Ahmed-Belkacem","year":"2005","unstructured":"Ahmed-Belkacem A, Pozza A, Munoz-Martinez F, Bates SE, Castanys S, Gamarro F, Di Pietro A, Perez-Victoria JM: Flavonoid structure-activity studies identify 6-prenylchrysin and tectochrysin as potent and specific inhibitors of breast cancer resistance protein ABCG2. Cancer Res. 2005, 65 (11): 4852-4860. 10.1158\/0008-5472.CAN-04-1817.","journal-title":"Cancer Res"},{"issue":"8","key":"5843_CR15","doi-asserted-by":"publisher","first-page":"1933","DOI":"10.1021\/jm061450q","volume":"50","author":"A Ahmed-Belkacem","year":"2007","unstructured":"Ahmed-Belkacem A, Macalou S, Borrelli F, Capasso R, Fattorusso E, Taglialatela-Scafati O, Di Pietro A: Nonprenylated rotenoids, a new class of potent breast cancer resistance protein inhibitors. J Med Chem. 2007, 50 (8): 1933-1938. 10.1021\/jm061450q.","journal-title":"J Med Chem"},{"issue":"1","key":"5843_CR16","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.canlet.2005.05.052","volume":"234","author":"H Nakagawa","year":"2006","unstructured":"Nakagawa H, Saito H, Ikegami Y, Aida-Hyugaji S, Sawada S, Ishikawa T: Molecular modeling of new camptothecin analogues to circumvent ABCG2-mediated drug resistance in cancer. Cancer Lett. 2006, 234 (1): 81-89. 10.1016\/j.canlet.2005.05.052.","journal-title":"Cancer Lett"},{"issue":"6","key":"5843_CR17","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1021\/ci2001583","volume":"51","author":"Z Wang","year":"2011","unstructured":"Wang Z, Chen Y, Liang H, Bender A, Glen RC, Yan A: P-glycoprotein substrate models using support vector machines based on a comprehensive data set. J Chem Inf Model. 2011, 51 (6): 1447-1456. 10.1021\/ci2001583.","journal-title":"J Chem Inf Model"},{"issue":"4","key":"5843_CR18","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1021\/ci049971e","volume":"44","author":"Y Xue","year":"2004","unstructured":"Xue Y, Yap CW, Sun LZ, Cao ZW, Wang JF, Chen YZ: Prediction of P-glycoprotein substrates by a support vector machine approach. J Chem Inf Comput Sci. 2004, 44 (4): 1497-1505. 10.1021\/ci049971e.","journal-title":"J Chem Inf Comput Sci"},{"issue":"4","key":"5843_CR19","doi-asserted-by":"publisher","first-page":"1638","DOI":"10.1021\/ci700083n","volume":"47","author":"J Huang","year":"2007","unstructured":"Huang J, Ma G, Muhammad I, Cheng Y: Identifying P-glycoprotein substrates using a support vector machine optimized by a particle swarm. J Chem Inf Model. 2007, 47 (4): 1638-1647. 10.1021\/ci700083n.","journal-title":"J Chem Inf Model"},{"issue":"10","key":"5843_CR20","doi-asserted-by":"publisher","first-page":"e25815","DOI":"10.1371\/journal.pone.0025815","volume":"6","author":"Z Bikadi","year":"2011","unstructured":"Bikadi Z, Hazai I, Malik D, Jemnitz K, Veres Z, Hari P, Ni Z, Loo TW, Clarke DM, Hazai E: Predicting P-glycoprotein-mediated drug transport based on support vector machine and three-dimensional crystal structure of P-glycoprotein. PLoS One. 2011, 6 (10): e25815-10.1371\/journal.pone.0025815.","journal-title":"PLoS One"},{"issue":"11","key":"5843_CR21","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1016\/j.compbiomed.2011.08.009","volume":"41","author":"L Zhong","year":"2011","unstructured":"Zhong L, Ma CY, Zhang H, Yang LJ, Wan HL, Xie QQ, Li LL, Yang SY: A prediction model of substrates and non-substrates of breast cancer resistance protein (BCRP) developed by GA-CG-SVM method. Comput Biol Med. 2011, 41 (11): 1006-1013. 10.1016\/j.compbiomed.2011.08.009.","journal-title":"Comput Biol Med"},{"key":"5843_CR22","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/1471-2210-10-8","volume":"10","author":"NK Mishra","year":"2010","unstructured":"Mishra NK, Agarwal S, Raghava GP: Prediction of cytochrome P450 isoform responsible for metabolizing a drug molecule. BMC Pharmacol. 2010, 10: 8-","journal-title":"BMC Pharmacol"},{"issue":"18","key":"5843_CR23","first-page":"6635","volume":"61","author":"Y Honjo","year":"2001","unstructured":"Honjo Y, Hrycyna CA, Yan QW, Medina-Perez WY, Robey RW, van de Laar A, Litman T, Dean M, Bates SE: Acquired mutations in the MXR\/BCRP\/ABCP gene alter substrate specificity in MXR\/BCRP\/ABCP-overexpressing cells. Cancer Res. 2001, 61 (18): 6635-6639.","journal-title":"Cancer Res"},{"issue":"10","key":"5843_CR24","doi-asserted-by":"publisher","first-page":"1971","DOI":"10.1038\/sj.bjc.6601370","volume":"89","author":"RW Robey","year":"2003","unstructured":"Robey RW, Honjo Y, Morisaki K, Nadjem TA, Runge S, Risbood M, Poruchynsky MS, Bates SE: Mutations at amino-acid 482 in the ABCG2 gene affect substrate and antagonist specificity. Br J Cancer. 2003, 89 (10): 1971-1978. 10.1038\/sj.bjc.6601370.","journal-title":"Br J Cancer"},{"issue":"1","key":"5843_CR25","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.bbamem.2004.11.005","volume":"1668","author":"C Ozvegy-Laczka","year":"2005","unstructured":"Ozvegy-Laczka C, Koblos G, Sarkadi B, Varadi A: Single amino acid (482) variants of the ABCG2 multidrug transporter: major differences in transport capacity and substrate recognition. Biochim Biophys Acta. 2005, 1668 (1): 53-63. 10.1016\/j.bbamem.2004.11.005.","journal-title":"Biochim Biophys Acta"},{"key":"5843_CR26","doi-asserted-by":"publisher","first-page":"3219","DOI":"10.1016\/0040-4020(80)80168-2","volume":"36","author":"JMM Gasteiger","year":"1980","unstructured":"Gasteiger JMM: Iterative partial equalization of orbital electronegativity - a rapid access to atomic charges. Tetrahedron. 1980, 36: 3219-3228. 10.1016\/0040-4020(80)80168-2.","journal-title":"Tetrahedron"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2105-14-130.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T23:34:31Z","timestamp":1630539271000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/1471-2105-14-130"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4,15]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["5843"],"URL":"https:\/\/doi.org\/10.1186\/1471-2105-14-130","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,4,15]]},"assertion":[{"value":"6 November 2012","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 April 2013","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 April 2013","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"130"}}