{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T01:04:32Z","timestamp":1777424672810,"version":"3.51.4"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2013,5,16]],"date-time":"2013-05-16T00:00:00Z","timestamp":1368662400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Cancer"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>It has been shown in many solid tumors that the overexpression of the pro-survival Bcl-2 family members Bcl-2\/Bcl-xL and Mcl-1 confers resistance to a variety of chemotherapeutic agents. We designed the BH3 \u03b1-helix mimetic JY-1-106 to engage the hydrophobic BH3-binding grooves on the surfaces of both Bcl-xL and Mcl-1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>JY-1-106\u2013protein complexes were studied using molecular dynamics (MD) simulations and the SILCS methodology. We have evaluated the in vitro effects of JY-1-106 by using a fluorescence polarization (FP) assay, an XTT assay, apoptosis assays, and immunoprecipitation and western-blot assays. A preclinical human cancer xenograft model was used to test the efficacy of JY-1-106 in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MD and SILCS simulations of the JY-1-106\u2013protein complexes indicated the importance of the aliphatic side chains of JY-1-106 to binding and successfully predicted the improved affinity of the ligand for Bcl-xL over Mcl-1. Ligand binding affinities were measured via an FP assay using a fluorescently labeled Bak-BH3 peptide<jats:italic>in vitro<\/jats:italic>. Apoptosis induction via JY-1-106 was evidenced by TUNEL assay and PARP cleavage as well as by Bax\u2013Bax dimerization. Release of multi-domain Bak from its inhibitory binding to Bcl-2\/Bcl-xL and Mcl-1 using JY-1-106 was detected via immunoprecipitation (IP) western blotting.<\/jats:p><jats:p>At the cellular level, we compared the growth proliferation IC<jats:sub>50<\/jats:sub>s of JY-1-106 and ABT-737 in multiple cancer cell lines with various Bcl-xL and Mcl-1 expression levels. JY-1-106 effectively induced cell death regardless of the Mcl-1 expression level in ABT-737 resistant solid tumor cells, whilst toxicity toward normal human endothelial cells was limited. Furthermore, synergistic effects were observed in A549 cells using a combination of JY-1-106 and multiple chemotherapeutic agents. We also observed that JY-1-106 was a very effective agent in inducing apoptosis in metabolically stressed tumors. Finally, JY-1-106 was evaluated in a tumor-bearing nude mouse model, and was found to effectively repress tumor growth. Strong TUNEL signals in the tumor cells demonstrated the effectiveness of JY-1-106 in this animal model. No significant side effects were observed in mouse organs after multiple injections.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Taken together, these observations demonstrate that JY-1-106 is an effective pan-Bcl-2 inhibitor with very promising clinical potential.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1476-4598-12-42","type":"journal-article","created":{"date-parts":[[2013,5,17]],"date-time":"2013-05-17T00:14:58Z","timestamp":1368749698000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["The novel BH3 \u03b1-helix mimetic JY-1-106 induces apoptosis in a subset of cancer cells (lung cancer, colon cancer and mesothelioma) by disrupting Bcl-xL and Mcl-1 protein\u2013protein interactions with Bak"],"prefix":"10.1186","volume":"12","author":[{"given":"Xiaobo","family":"Cao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy L","family":"Yap","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M Karen","family":"Newell-Rogers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chander","family":"Peddaboina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weihua","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harry T","family":"Papaconstantinou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Jupitor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arun","family":"Rai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwan-Young","family":"Jung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard P","family":"Tubin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenbo","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenno","family":"Vanommeslaeghe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul T","family":"Wilder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"JR","given":"Alexander D","family":"MacKerell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Fletcher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roy W","family":"Smythe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,5,16]]},"reference":[{"key":"1111_CR1","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1038\/348334a0","volume":"348","author":"D Hockenbery","year":"1990","unstructured":"Hockenbery D, Nunez G, Milliman C, Schreiber RD, Korsmeyer SJ: Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature. 1990, 348: 334-336. 10.1038\/348334a0","journal-title":"Nature"},{"key":"1111_CR2","first-page":"6101","volume":"60","author":"SA Amundson","year":"2000","unstructured":"Amundson SA, Myers TG, Scudiero D, Kitada S, Reed JC, Fornace AJ: An informatics approach identifying markers of chemosensitivity in human cancer cell lines. Cancer Res. 2000, 60: 6101-6110.","journal-title":"Cancer Res"},{"key":"1111_CR3","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1038\/nature03579","volume":"435","author":"T Oltersdorf","year":"2005","unstructured":"Oltersdorf T, Elmore SW, Shoemaker AR, Armstrong RC, Augeri DJ, Belli BA, Bruncko M, Deckwerth TL, Dinges J, Hajduk PJ: An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature. 2005, 435: 677-681. 10.1038\/nature03579","journal-title":"Nature"},{"key":"1111_CR4","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1158\/1535-7163.MCT-11-0693","volume":"11","author":"M Wong","year":"2012","unstructured":"Wong M, Tan N, Zha J, Peale FV, Yue P, Fairbrother WJ, Belmont LD: Navitoclax (ABT-263) reduces Bcl-x(L)-mediated chemoresistance in ovarian cancer models. Mol Cancer Ther. 2012, 11: 1026-1035. 10.1158\/1535-7163.MCT-11-0693","journal-title":"Mol Cancer Ther"},{"key":"1111_CR5","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1186\/1471-2407-12-541","volume":"12","author":"C Peddaboina","year":"2012","unstructured":"Peddaboina C, Jupiter D, Fletcher S, Yap JL, Rai A, Tobin R, Jiang W, Rascoe P, Rogers MK, Smythe WR, Cao X: The downregulation of Mcl-1 via USP9X inhibition sensitizes solid tumors to Bcl-xl inhibition. BMC Cancer. 2012, 12: 541- 10.1186\/1471-2407-12-541","journal-title":"BMC Cancer"},{"key":"1111_CR6","doi-asserted-by":"publisher","first-page":"e12","DOI":"10.1017\/erm.2012.6","volume":"14","author":"PA Rascoe","year":"2012","unstructured":"Rascoe PA, Jupiter D, Cao X, Littlejohn JE, Smythe WR: Molecular pathogenesis of malignant mesothelioma. Expert Rev Mol Med. 2012, 14: e12-","journal-title":"Expert Rev Mol Med"},{"key":"1111_CR7","doi-asserted-by":"publisher","first-page":"2226","DOI":"10.1158\/1078-0432.CCR-06-1574","volume":"13","author":"RM Mohammad","year":"2007","unstructured":"Mohammad RM, Goustin AS, Aboukameel A, Chen B, Banerjee S, Wang G, Nikolovska-Coleska Z, Wang S, Al-Katib A: Preclinical studies of TW-37, a new nonpeptidic small-molecule inhibitor of Bcl-2, in diffuse large cell lymphoma xenograft model reveal drug action on both Bcl-2 and Mcl-1. Clin Cancer Res. 2007, 13: 2226-2235. 10.1158\/1078-0432.CCR-06-1574","journal-title":"Clin Cancer Res"},{"key":"1111_CR8","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.jmb.2007.06.069","volume":"372","author":"W Feng","year":"2007","unstructured":"Feng W, Huang S, Wu H, Zhang M: Molecular basis of Bcl-xL\u2019s target recognition versatility revealed by the structure of Bcl-xL in complex with the BH3 domain of Beclin-1. J Mol Biol. 2007, 372: 223-235. 10.1016\/j.jmb.2007.06.069","journal-title":"J Mol Biol"},{"key":"1111_CR9","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1517\/14728214.2010.515210","volume":"16","author":"AS Azmi","year":"2011","unstructured":"Azmi AS, Wang Z, Philip PA, Mohammad RM, Sarkar FH: Emerging Bcl-2 inhibitors for the treatment of cancer. Expert Opin Emerg Drugs. 2011, 16: 59-70. 10.1517\/14728214.2010.515210","journal-title":"Expert Opin Emerg Drugs"},{"key":"1111_CR10","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.3390\/cancers3021527","volume":"3","author":"A Masood","year":"2011","unstructured":"Masood A, Azmi AS, Mohammad RM: Small molecule inhibitors of Bcl-2 family proteins for pancreatic cancer therapy. Cancers (Basel). 2011, 3: 1527-1549. 10.3390\/cancers3021527.","journal-title":"Cancers (Basel)"},{"key":"1111_CR11","doi-asserted-by":"publisher","first-page":"6","DOI":"10.2174\/1874196701205010006","volume":"5","author":"R-G Hawley","year":"2012","unstructured":"Hawley R-G, Chen Y, Riz I, Zeng C: An Integrated Bioinformatics and Computational Biology Approach Identifies New BH3-Only Protein Candidates. Open Biol J. 2012, 5: 6-16. 10.2174\/1874196701205010006","journal-title":"Open Biol J"},{"key":"1111_CR12","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1126\/science.275.5302.983","volume":"275","author":"M Sattler","year":"1997","unstructured":"Sattler M, Liang H, Nettesheim D, Meadows RP, Harlan JE, Eberstadt M, Yoon HS, Shuker SB, Chang BS, Minn AJ, Thompson CB, Fesik SW:Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis. Science. 1997, 275: 983-986. 10.1126\/science.275.5302.983","journal-title":"Science"},{"key":"1111_CR13","doi-asserted-by":"publisher","first-page":"9382","DOI":"10.1074\/jbc.M110.203638","volume":"286","author":"A Kazi","year":"2011","unstructured":"Kazi A, Sun J, Doi K, Sung SS, Takahashi Y, Yin H, Rodriguez JM, Becerril J, Berndt N, Hamilton AD, Wang HG, Sebti SM: The BH3 \u03b1-Helical Mimic BH3-M6 Disrupts Bcl-XL, Bcl-2, and MCL-1 Protein-Protein Interactions with Bax, Bak, Bad, or Bim and Induces Apoptosis in a Bax- and Bim-dependent Manner. J Biol Chem. 2011, 286: 9382-9392. 10.1074\/jbc.M110.203638","journal-title":"J Biol Chem"},{"key":"1111_CR14","doi-asserted-by":"publisher","first-page":"8502","DOI":"10.1021\/jm3010306","volume":"55","author":"J Chen","year":"2012","unstructured":"Chen J, Zhou H, Aguilar A, Liu L, Bai L, McEachern D, Yang CY, Meagher JL, Stuckey JA, Wang S: Structure-based discovery of BM-957 as a potent small-molecule inhibitor of Bcl-2 and Bcl-xL capable of achieving complete tumor regression. J Med Chem. 2012, 55: 8502-8514. 10.1021\/jm3010306","journal-title":"J Med Chem"},{"key":"1111_CR15","doi-asserted-by":"publisher","first-page":"2928","DOI":"10.1039\/c2ob07125h","volume":"10","author":"JL Yap","year":"2012","unstructured":"Yap JL, Cao X, Vanommeslaeghe K, Jung KY, Peddaboina C, Wilder PT, Nan A, MacKerell AD, Smythe WR, Fletcher S: Relaxation of the rigid backbone of an oligoamide-foldamer-based alpha-helix mimetic: identification of potent Bcl-xL inhibitors. Org Biomol Chem. 2012, 10: 2928-2933. 10.1039\/c2ob07125h","journal-title":"Org Biomol Chem"},{"key":"1111_CR16","doi-asserted-by":"publisher","first-page":"e1000435","DOI":"10.1371\/journal.pcbi.1000435","volume":"5","author":"O Guvench","year":"2009","unstructured":"Guvench O, MacKerell AD: Computational Fragment-Based Binding Site Identification by Ligand Competitive Saturation. PLoS Comput Biol. 2009, 5: e1000435- 10.1371\/journal.pcbi.1000435","journal-title":"PLoS Comput Biol"},{"key":"1111_CR17","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1021\/ci100462t","volume":"51","author":"EP Raman","year":"2011","unstructured":"Raman EP, Yu W, Guvench O, MacKerell AD: Reproducing Crystal Binding Modes of Ligand Functional Groups Using Site-Identification by Ligand Competitive Saturation (SILCS) Simulations. J Chem Inf Model. 2011, 51: 877-896. 10.1021\/ci100462t","journal-title":"J Chem Inf Model"},{"key":"1111_CR18","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1021\/ml200301w","volume":"3","author":"C-Y Yang","year":"2012","unstructured":"Yang C-Y, Wang S: Analysis of Flexibility and Hotspots in Bcl-xL and Mcl-1 Proteins for the Design of Selective Small-Molecule Inhibitors. ACS Med Chem Lett. 2012, 3: 308-312. 10.1021\/ml200301w.","journal-title":"ACS Med Chem Lett"},{"key":"1111_CR19","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1007\/978-1-62703-236-0_8","volume-title":"p53 Protocols. Volume 962","author":"Q Zhang","year":"2013","unstructured":"Zhang Q, Lu H: Identification of Small Molecules Affecting p53-MDM2\/MDMX Interaction by Fluorescence Polarization. p53 Protocols. Volume 962. 2013, 95-111. Humana Press; Methods in Molecular Biology."},{"key":"1111_CR20","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/369321a0","volume":"369","author":"XM Yin","year":"1994","unstructured":"Yin XM, Oltvai ZN, Korsmeyer SJ: BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax. Nature. 1994, 369: 321-333. 10.1038\/369321a0","journal-title":"Nature"},{"key":"1111_CR21","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1016\/j.jmb.2008.05.071","volume":"380","author":"CL Day","year":"2008","unstructured":"Day CL, Smits C, Fan FC, Lee EF, Fairlie WD, Hinds MG: Structure of the BH3 Domains from the p53-Inducible BH3-Only Proteins Noxa and Puma in Complex with Mcl-1. J Mol Biol. 2008, 380: 958-971. 10.1016\/j.jmb.2008.05.071","journal-title":"J Mol Biol"},{"key":"1111_CR22","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1177\/1947601911417177","volume":"2","author":"R Elkholi","year":"2011","unstructured":"Elkholi R, Floros KV, Chipuk JE: The Role of BH3-Only Proteins in Tumor Cell Development, Signaling, and Treatment. Genes & Cancer. 2011, 2: 523-537. 10.1177\/1947601911417177","journal-title":"Genes & Cancer"},{"key":"1111_CR23","doi-asserted-by":"publisher","first-page":"7985","DOI":"10.1158\/0008-5472.CAN-08-1418","volume":"68","author":"O Kutuk","year":"2008","unstructured":"Kutuk O, Letai A: Alteration of the Mitochondrial Apoptotic Pathway Is Key to Acquired Paclitaxel Resistance and Can Be Reversed by ABT-737. Cancer Res. 2008, 68: 7985-7994. 10.1158\/0008-5472.CAN-08-1418","journal-title":"Cancer Res"},{"key":"1111_CR24","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/j.bbamcr.2010.08.011","volume":"1813","author":"EF Mason","year":"2011","unstructured":"Mason EF, Rathmell JC: Cell metabolism: An essential link between cell growth and apoptosis. Biochimica et Biophysica Acta (BBA) Molecular Cell Research. 2011, 1813: 645-654. 10.1016\/j.bbamcr.2010.08.011.","journal-title":"Biochimica et Biophysica Acta (BBA) Molecular Cell Research"},{"key":"1111_CR25","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1038\/ncb2330","volume":"13","author":"KN Alavian","year":"2011","unstructured":"Alavian KN, Li H, Collis L, Bonanni L, Zeng L, Sacchetti S, Lazrove E, Nabili P, Flaherty B, Graham M: Bcl-xL regulates metabolic efficiency of neurons through interaction with the mitochondrial F1FO ATP synthase. Nat Cell Biol. 2011, 13: 1224-1233. 10.1038\/ncb2330","journal-title":"Nat Cell Biol"},{"key":"1111_CR26","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1038\/ncb2488","volume":"14","author":"RM Perciavalle","year":"2012","unstructured":"Perciavalle RM, Stewart DP, Koss B, Lynch J, Milasta S, Bathina M, Temirov J, Cleland MM, Pelletier S, Schuetz JD: Anti-apoptotic MCL-1 localizes to the mitochondrial matrix and couples mitochondrial fusion to respiration. Nat Cell Biol. 2012, 14: 575-583. 10.1038\/ncb2488","journal-title":"Nat Cell Biol"},{"key":"1111_CR27","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1002\/jcc.21287","volume":"30","author":"BR Brooks","year":"2009","unstructured":"Brooks BR, Brooks CL, Mackerell AD, Nilsson L, Petrella RJ, Roux B, Won Y, Archontis G, Bartels C, Boresch S: CHARMM: the biomolecular simulation program. J Comput Chem. 2009, 30: 1545-1614. 10.1002\/jcc.21287","journal-title":"J Comput Chem"},{"key":"1111_CR28","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1002\/jcc.20289","volume":"26","author":"JC Phillips","year":"2005","unstructured":"Phillips JC, Braun R, Wang W, Gumbart J, Tajkhorshid E, Villa E, Chipot C, Skeel RD, Kal\u00e9 L, Schulten K: Scalable molecular dynamics with NAMD. J Comput Chem. 2005, 26: 1781-1802. 10.1002\/jcc.20289","journal-title":"J Comput Chem"},{"key":"1111_CR29","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1002\/jcc.21367","volume":"31","author":"K Vanommeslaeghe","year":"2010","unstructured":"Vanommeslaeghe K, Hatcher E, Acharya C, Kundu S, Zhong S, Shim J, Darian E, Guvench O, Lopes P, Vorobyov I, Mackerell AD: CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields. J Comput Chem. 2010, 31: 671-690.","journal-title":"J Comput Chem"},{"key":"1111_CR30","doi-asserted-by":"publisher","first-page":"2451","DOI":"10.1002\/jcc.23067","volume":"33","author":"W Yu","year":"2012","unstructured":"Yu W, He X, Vanommeslaeghe K, MacKerell AD: Extension of the CHARMM general force field to sulfonyl-containing compounds and its utility in biomolecular simulations. J Comput Chem. 2012, 33: 2451-2468. 10.1002\/jcc.23067","journal-title":"J Comput Chem"},{"key":"1111_CR31","doi-asserted-by":"publisher","first-page":"3513","DOI":"10.1021\/ct300088r","volume":"8","author":"EP Raman","year":"2012","unstructured":"Raman EP, Vanommeslaeghe K, Mackerell AD: Site-specific fragment identification guided by single-step free energy perturbation calculations. J Chem Theory Comput. 2012, 8: 3513-3525. 10.1021\/ct300088r","journal-title":"J Chem Theory Comput"},{"key":"1111_CR32","doi-asserted-by":"publisher","first-page":"3586","DOI":"10.1021\/jp973084f","volume":"102","author":"AD MacKerell","year":"1998","unstructured":"MacKerell AD, Bashford D, Bellott T, Dunbrack RL, Evanseck JD, Field MJ, Fischer S, Gao J, Guo H, Ha S: All-atom empirical potential for molecular modeling and dynamics studies of proteins?. J Phys Chem B. 1998, 102: 3586-3616. 10.1021\/jp973084f.","journal-title":"J Phys Chem B"},{"key":"1111_CR33","doi-asserted-by":"publisher","first-page":"e48817","DOI":"10.1371\/journal.pone.0048817","volume":"7","author":"A Cossu","year":"2012","unstructured":"Cossu A, Posadino AM, Giordo R, Emanueli C, Sanguinetti AM, Piscopo A, Poiana M, Capobianco G, Piga A, Pintus G: Apricot melanoidins prevent oxidative endothelial cell death by counteracting mitochondrial oxidation and membrane depolarization. PLoS One. 2012, 7: e48817- 10.1371\/journal.pone.0048817","journal-title":"PLoS One"}],"container-title":["Molecular Cancer"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1476-4598-12-42.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1476-4598-12-42\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1476-4598-12-42.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T20:58:51Z","timestamp":1715374731000},"score":1,"resource":{"primary":{"URL":"https:\/\/molecular-cancer.biomedcentral.com\/articles\/10.1186\/1476-4598-12-42"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5,16]]},"references-count":33,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["1111"],"URL":"https:\/\/doi.org\/10.1186\/1476-4598-12-42","relation":{},"ISSN":["1476-4598"],"issn-type":[{"value":"1476-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,5,16]]},"assertion":[{"value":"20 February 2013","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 May 2013","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 May 2013","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"42"}}