{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T21:15:44Z","timestamp":1788383744296,"version":"build-2803163510"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2021,1,3]],"date-time":"2021-01-03T00:00:00Z","timestamp":1609632000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2021,1,3]],"date-time":"2021-01-03T00:00:00Z","timestamp":1609632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology , Ministry of Science and Technology","doi-asserted-by":"publisher","award":["BT\/PR14554\/INF\/22\/125\/2010"],"award-info":[{"award-number":["BT\/PR14554\/INF\/22\/125\/2010"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pharmacol. Rep"],"published-print":{"date-parts":[[2021,4]]},"DOI":"10.1007\/s43440-020-00196-x","type":"journal-article","created":{"date-parts":[[2021,1,3]],"date-time":"2021-01-03T09:02:59Z","timestamp":1609664579000},"page":"615-628","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Repositioning antispasmodic drug Papaverine for the treatment of chronic myeloid leukemia"],"prefix":"10.1007","volume":"73","author":[{"given":"Phani Krishna","family":"Parcha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sailu","family":"Sarvagalla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheemala","family":"Ashok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. J.","family":"Sudharshan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhu","family":"Dyavaiah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0505-568X","authenticated-orcid":false,"given":"Mohane Selvaraj","family":"Coumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baskaran","family":"Rajasekaran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,3]]},"reference":[{"key":"196_CR1","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/243290a0","volume":"243","author":"JD Rowley","year":"1973","unstructured":"Rowley JD. A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature. 1973;243:290\u20133.","journal-title":"Nature"},{"key":"196_CR2","doi-asserted-by":"publisher","first-page":"2033","DOI":"10.1172\/JCI31771","volume":"117","author":"PC Nowell","year":"2007","unstructured":"Nowell PC. Discovery of the Philadelphia chromosome: a personal perspective. J Clin Invest. 2007;117:2033\u20135.","journal-title":"J Clin Invest."},{"key":"196_CR3","doi-asserted-by":"publisher","first-page":"8541","DOI":"10.1038\/sj.onc.1206081","volume":"21","author":"BJ Druker","year":"2002","unstructured":"Druker BJ. Inhibition of the Bcr-Abl tyrosine kinase as a therapeutic strategy for CML. Oncogene. 2002;21:8541\u20136.","journal-title":"Oncogene"},{"key":"196_CR4","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1126\/science.2408149","volume":"247","author":"TG Lugo","year":"1990","unstructured":"Lugo TG, Pendergast AM, Muller AJ, Witte ON. Tyrosine kinase activity and transformation potency of Bcr-Abl oncogene products. Science. 1990;247:1079\u201382.","journal-title":"Science"},{"key":"196_CR5","doi-asserted-by":"publisher","first-page":"2333","DOI":"10.1038\/sj.onc.1201400","volume":"15","author":"D Cortez","year":"1997","unstructured":"Cortez D, Reuther G, Pendergast AM. The Bcr-Abl tyrosine kinase activates mitogenic signaling pathways and stimulates G1-to-S phase transition in hematopoietic cells. Oncogene. 1997;15:2333\u201342.","journal-title":"Oncogene"},{"key":"196_CR6","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/nrd839","volume":"1","author":"R Capdeville","year":"2002","unstructured":"Capdeville R, Buchdunger E, Zimmermann J, Matter A. Glivec (STI571, Imatinib), a rationally developed, targeted anti-cancer drug. Nat Rev Drug Discov. 2002;1:493\u2013502.","journal-title":"Nat Rev Drug Discov."},{"key":"196_CR7","first-page":"3047","volume":"1848","author":"P Pophali","year":"2016","unstructured":"Pophali P, Patnaik M. The Role of New Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia. Cancer J. 2016;1848:3047\u201354.","journal-title":"Cancer J."},{"key":"196_CR8","doi-asserted-by":"publisher","first-page":"4","DOI":"10.3390\/vetsci3010004","volume":"3","author":"N Dervisis","year":"2016","unstructured":"Dervisis N, Klahn S. Therapeutic Innovations: Tyrosine Kinase Inhibitors in Cancer. Vet Sci. 2016;3:4.","journal-title":"Vet Sci."},{"key":"196_CR9","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1158\/1078-0432.CCR-09-3314","volume":"17","author":"T O\u2019Hare","year":"2011","unstructured":"O\u2019Hare T, Deininger MWN, Eide CA, Clackson T, Druker BJ. Targeting the BCR\u2013ABL signaling pathway in therapy-resistant Philadelphia chromosome-positive leukemia. Clin Cancer Res. 2011;17:212\u201321.","journal-title":"Clin Cancer Res."},{"key":"196_CR10","first-page":"328","volume":"3","author":"N Hasima","year":"2012","unstructured":"Hasima N, Aggarwal BB. Cancer-linked targets modulated by curcumin. IJBMB. 2012;3:328\u201351.","journal-title":"IJBMB"},{"key":"196_CR11","doi-asserted-by":"publisher","first-page":"1937","DOI":"10.1039\/c1np00051a","volume":"28","author":"SC Gupta","year":"2011","unstructured":"Gupta SC, Prasad S, Kim JH, Patchva S, Webb LJ, Priyadarsini IK, et al. Multitargeting by curcumin as revealed by molecular interaction studies. Nat Prod Rep. 2011;28:1937\u201355.","journal-title":"Nat Prod Rep."},{"key":"196_CR12","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1038\/nrd1468","volume":"3","author":"TT Ashburn","year":"2004","unstructured":"Ashburn TT, Thor KB. Drug repositioning: identifying and developing new uses for existing drugs. Nat Rev Drug Discov. 2004;3:673\u201383.","journal-title":"Nat Rev Drug Discov."},{"key":"196_CR13","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1093\/pcp\/pct020","volume":"54","author":"JM Hagel","year":"2013","unstructured":"Hagel JM, Facchini PJ. Benzylisoquinoline alkaloid metabolism\u2013a century of discovery and a brave new world. Plant Cell Physiol. 2013;54:647\u201372.","journal-title":"Plant Cell Physiol."},{"key":"196_CR14","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1385\/NCC:2:2:124","volume":"2","author":"JK Liu","year":"2005","unstructured":"Liu JK, Couldwell WT. Intra-arterial papaverine infusions for the treatment of cerebral vasospasm induced by aneurysmal subarachnoid hemorrhage. Neurocrit Care. 2005;2:124\u201332.","journal-title":"Neurocrit Care."},{"key":"196_CR15","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1097\/00005392-199502000-00019","volume":"153","author":"ED Kim","year":"1995","unstructured":"Kim ED, El-Rashidy R, McVary KT. Papaverine topical gel for treatment of erectile dysfunction. J Urol. 1995;153:361\u20135.","journal-title":"J Urol."},{"key":"196_CR16","first-page":"1","volume":"21","author":"SA Mindea","year":"2006","unstructured":"Mindea SA, Yang BP, Bendok BR, Miller JW, Batjer HH. Endovascular treatment strategies for cerebral vasospasm. Neurosurg Focus. 2006;21:1\u20137.","journal-title":"Neurosurg Focus."},{"key":"196_CR17","doi-asserted-by":"publisher","first-page":"388","DOI":"10.3109\/15376516.2015.1045656","volume":"25","author":"S Sajadian","year":"2015","unstructured":"Sajadian S, Vatankhah M, Majdzadeh M, Kouhsari SM, Ghahremani MH, Ostad SN. Cell cycle arrest and apoptogenic properties of opium alkaloids noscapine and Papaverine on breast cancer stem cells. Toxicol Mech Methods. 2015;25:388\u201395.","journal-title":"Toxicol Mech Methods."},{"key":"196_CR18","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s40199-015-0101-1","volume":"23","author":"M Afzali","year":"2015","unstructured":"Afzali M, Ghaeli P, Khanavi M, Parsa M, Montazeri H, Ghahremani MH, et al. Non-addictive opium alkaloids selectively induce apoptosis in cancer cells compared to normal cells. Daru. 2015;23:16.","journal-title":"Daru."},{"key":"196_CR19","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1002\/biof.5520250110","volume":"25","author":"H Nohl","year":"2005","unstructured":"Nohl H, Rohr-Udilova N, Gille L, Bieberschulte W, Jurek D, Marian B, et al. Ubiquinol and the papaverine derivative caroverine prevent the expression of tumour-promoting factors in adenoma and carcinoma colon cancer cells induced by dietary fat. BioFactors. 2005;25:87\u201395.","journal-title":"BioFactors"},{"key":"196_CR20","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1007\/s10637-008-9173-9","volume":"27","author":"B Rubis","year":"2009","unstructured":"Rubis B, Kaczmarek M, Szymanowska N, Galezowska E, Czyrski A, Juskowiak B, et al. The biological activity of G-quadruplex DNA binding papaverine-derived ligand in breast cancer cells. Invest New Drugs. 2009;27:289\u201396.","journal-title":"Invest New Drugs."},{"key":"196_CR21","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1007\/s00284-017-1412-x","volume":"75","author":"P Alugoju","year":"2018","unstructured":"Alugoju P, Janardhanshetty SS, Subaramanian S, Periyasamy L, Dyavaiah M. Quercetin protects yeast saccharomyces cerevisiae pep4 mutant from oxidative and apoptotic stress and extends chronological lifespan. Curr Microbiol. 2018;75:519\u201330.","journal-title":"Curr Microbiol."},{"key":"196_CR22","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1093\/jnci\/djn188","volume":"100","author":"J Wu","year":"2008","unstructured":"Wu J, Meng F, Kong LY, Peng Z, Ying Y, Bornmann WG, et al. Association between imatinib-resistant BCR\u2013ABL mutation-negative leukemia and persistent activation of LYN kinase. J Natl Cancer Inst. 2008;100:926\u201339.","journal-title":"J Natl Cancer Inst."},{"key":"196_CR23","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1111\/cbdd.12983","volume":"90","author":"P Parcha","year":"2017","unstructured":"Parcha P, Sarvagalla S, Madhuri B, Pajaniradje S, Baskaran V, Coumar MS, et al. Identification of natural inhibitors of Bcr-Abl for the treatment of chronic myeloid leukemia. Chem Biol Drug Des. 2017;90:596\u2013608.","journal-title":"Chem Biol Drug Des."},{"key":"196_CR24","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1007\/s10822-014-9807-2","volume":"29","author":"S Sarvagalla","year":"2015","unstructured":"Sarvagalla S, Singh VK, Ke YY, Shiao HY, Lin WH, Hsieh HP, et al. Identification of ligand efficient, fragment-like hits from an HTS library: Structure-based virtual screening and docking investigations of 2H- and 3H-pyrazolo tautomers for Aurora kinase A selectivity. J Comput Aided Mol Des. 2015;29:89\u2013100.","journal-title":"J Comput Aided Mol Des."},{"key":"196_CR25","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1158\/0008-5472.CAN-09-1947","volume":"70","author":"TC Chou","year":"2010","unstructured":"Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 2010;70:440\u20136.","journal-title":"Cancer Res."},{"key":"196_CR26","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.phymed.2017.08.006","volume":"34","author":"S Galadari","year":"2017","unstructured":"Galadari S, Rahman A, Pallichankandy S, Thayyullathil F. Molecular targets and anti-cancer potential of sanguinarine\u2014a benzophenanthridine alkaloid. Phytomedicine. 2017;34:143\u201353.","journal-title":"Phytomedicine"},{"key":"196_CR27","doi-asserted-by":"publisher","first-page":"367","DOI":"10.2174\/1570193X113106660031","volume":"10","author":"J Skrabalova","year":"2013","unstructured":"Skrabalova J, Drastichova Z, Novotny J. Morphine as a potential oxidative stress-causing agent. Mini Rev Org Chem. 2013;10:367\u201372.","journal-title":"Mini Rev Org Chem."},{"key":"196_CR28","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1002\/med.21357","volume":"35","author":"PCG Rida","year":"2015","unstructured":"Rida PCG, Livecche D, Ogden A, Zhou J, Aneja R. The noscapine chronicle: a pharmaco-historic biography of the opiate alkaloid family and its clinical applications. Med Res Rev. 2015;35:1072\u201396.","journal-title":"Med Res Rev."},{"key":"196_CR29","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/s41392-018-0018-5","volume":"3","author":"Q Chen","year":"2018","unstructured":"Chen Q, Kang J, Fu C. The independence of and associations among apoptosis, autophagy, and necrosis. Signal Transduct Target Ther. 2018;3:18.","journal-title":"Signal Transduct Target Ther."},{"key":"196_CR30","doi-asserted-by":"publisher","first-page":"64","DOI":"10.3389\/fonc.2012.00064","volume":"2","author":"G Farrugia","year":"2012","unstructured":"Farrugia G, Balzan R. Oxidative stress and programmed cell death in yeast. Front Oncol. 2012;2:64.","journal-title":"Front Oncol."},{"key":"196_CR31","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1016\/j.cell.2006.06.040","volume":"126","author":"AB Parsons","year":"2006","unstructured":"Parsons AB, Lopez A, Givoni IE, Williams DE, Gray CA, Porter J, et al. Exploring the mode-of-action of bioactive compounds by chemical-genetic profiling in yeast. Cell. 2006;126:611\u201325.","journal-title":"Cell"},{"key":"196_CR32","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1016\/j.cell.2012.11.046","volume":"152","author":"AR Reddi","year":"2013","unstructured":"Reddi AR, Culotta VC. SOD1 integrates signals from oxygen and glucose to repress respiration. Cell. 2013;152:224\u201335.","journal-title":"Cell"},{"key":"196_CR33","first-page":"1327","volume":"127","author":"AJ Weids","year":"2014","unstructured":"Weids AJ, Grant CM. The yeast peroxiredoxin Tsa1 protects against protein-aggregate-induced oxidative stress. J Cell Sci. 2014;127:1327\u201335.","journal-title":"J Cell Sci."},{"key":"196_CR34","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1016\/j.redox.2013.12.019","volume":"2","author":"D Martins","year":"2014","unstructured":"Martins D, English AM. Catalase activity is stimulated by H2O2 in rich culture medium and is required for H2O2 resistance and adaptation in yeast. Redox Biol. 2014;2:308\u201313.","journal-title":"Redox Biol."},{"key":"196_CR35","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.1111\/j.1365-2958.2010.07122.x","volume":"76","author":"C Pereira","year":"2010","unstructured":"Pereira C, Chaves S, Alves S, Salin B, Camougrand N, Manon S, et al. Mitochondrial degradation in acetic acid-induced yeast apoptosis: the role of Pep4 and the ADP\/ATP carrier. Mol Microbiol. 2010;76:1398\u2013410.","journal-title":"Mol Microbiol."},{"key":"196_CR36","doi-asserted-by":"publisher","first-page":"2935","DOI":"10.1016\/j.febslet.2007.05.048","volume":"581","author":"H Kitagaki","year":"2007","unstructured":"Kitagaki H, Araki Y, Funato K, Shimoi H. Ethanol-induced death in yeast exhibits features of apoptosis mediated by mitochondrial fission pathway. FEBS Lett. 2007;581:2935\u201342.","journal-title":"FEBS Lett."},{"key":"196_CR37","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1038\/cdd.2009.219","volume":"17","author":"D Carmona-Gutierrez","year":"2010","unstructured":"Carmona-Gutierrez D, Eisenberg T, B\u00fcttner S, Meisinger C, Kroemer G, Madeo F. Apoptosis in yeast: Triggers, pathways, subroutines. Cell Death Differ. 2010;17:763\u201373.","journal-title":"Cell Death Differ."},{"key":"196_CR38","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1182\/blood-2004-12-4704","volume":"107","author":"BZ Carter","year":"2006","unstructured":"Carter BZ, Mak DH, Schober WD, Cabreira-Hansen M, Beran M, McQueen T, et al. Regulation of survivin expression through Bcr\u2013Abl\/MAPK cascade: targeting survivin overcomes imatinib resistance and increases imatinib sensitivity in imatinib-responsive CML cells. Blood. 2006;107:1555\u201363.","journal-title":"Blood"},{"key":"196_CR39","doi-asserted-by":"publisher","first-page":"9540","DOI":"10.1073\/pnas.92.21.9540","volume":"92","author":"DEH Afar","year":"1995","unstructured":"Afar DEH, Mclaughlin J, Sherr CJ, Witte ON, Roussel MF. Signaling by ABL oncogenes through cyclin D1. Proc Natl Acad Sci USA. 1995;92:9540\u20134.","journal-title":"Proc Natl Acad Sci USA"},{"key":"196_CR40","doi-asserted-by":"publisher","first-page":"417","DOI":"10.3324\/haematol.2013.098442","volume":"99","author":"S Bibi","year":"2014","unstructured":"Bibi S, Arslanhan MD, Langenfeld F, Jeanningros S, Cerny-Reiterer S, Hadzijusufovic E, et al. Co-operating STAT5 and AKT signaling pathways in chronic myeloid leukemia and mastocytosis: possible new targets of therapy. Haematologica. 2014;99:417\u201329.","journal-title":"Haematologica"},{"key":"196_CR41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms19082396","volume":"19","author":"S Mirabilii","year":"2018","unstructured":"Mirabilii S, Ricciardi MR, Piedimonte M, Gianfelici V, Bianchi MP, Tafuri A. Biological aspects of mTOR in leukemia. Int J Mol Sci. 2018;19:1\u201320.","journal-title":"Int J Mol Sci."},{"key":"196_CR42","doi-asserted-by":"crossref","unstructured":"Geyer R, Zlateva T, Lakshmikuttyamma A, Sheridan DP, DeCoteau JF. GNF-2, An Allosteric BCR\u2013ABL inhibitor, identifies a novel myristoylation-mediated mechanism regulating the ability of BCR\u2013ABL to activate HCK and IGF-1 signaling. Blood. 2009;114.","DOI":"10.1182\/blood.V114.22.40.40"},{"key":"196_CR43","doi-asserted-by":"publisher","first-page":"4122","DOI":"10.1182\/blood-2002-10-3208","volume":"101","author":"EY Moon","year":"2003","unstructured":"Moon EY, Lerner A. PDE4 inhibitors activate a mitochondrial apoptotic pathway in chronic lymphocytic leukemia cells that is regulated by protein phosphatase 2A. Blood. 2003;101:4122\u201330.","journal-title":"Blood"}],"container-title":["Pharmacological Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43440-020-00196-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s43440-020-00196-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43440-020-00196-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T09:28:18Z","timestamp":1674811698000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s43440-020-00196-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,3]]},"references-count":43,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["196"],"URL":"https:\/\/doi.org\/10.1007\/s43440-020-00196-x","relation":{},"ISSN":["1734-1140","2299-5684"],"issn-type":[{"value":"1734-1140","type":"print"},{"value":"2299-5684","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,3]]},"assertion":[{"value":"20 February 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 November 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 November 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 January 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}