{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T06:01:17Z","timestamp":1760853677467},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Infect Agents Cancer"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Bcr-Abl plays a central role in the development of chromosome positive leukaemia. Chronic Myeloid leukaemia occurs due to increase proliferation and resistance to apoptosis by Bcr-Abl positive cells. Imatinib (STI571) is the first drug in the family of Bcr-Abl tyrosine kinase inhibitors while Nilotinib (AMN107) and Dasatinib (BMS-345825) are second generation drugs that are intended to have less resistance and intolerance than imatinib. Ponatinib (AP24534) an orally active Bcr-Abl Tyrosine Kinase Inhibitor and Bafetinib (INNO-406) have efficacy against various point mutations in the Bcr-Abl kinase. 1, 3, 4 thiadiazole derivatives has also displayed moderate inhibitory action on both Abl and Src kinase family. However there are varieties of Bcr-Abl inhibitors but Nilotinib is still the frontline tyrosine kinase inhibitors.<\/jats:p>","DOI":"10.1186\/1750-9378-8-23","type":"journal-article","created":{"date-parts":[[2013,6,20]],"date-time":"2013-06-20T08:14:29Z","timestamp":1371716069000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Bcr-Abl tyrosine kinase inhibitors- current status"],"prefix":"10.1186","volume":"8","author":[{"given":"Anum","family":"Mughal","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hafiz Muhammad","family":"Aslam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aga Muhammad Hammad","family":"Khan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shafaq","family":"Saleem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ribak","family":"Umah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Saleem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,6,20]]},"reference":[{"issue":"51","key":"443_CR1","first-page":"103","volume":"132","author":"P Nowell","year":"2004","unstructured":"Nowell P, Hungerford D: A minute chromosome in human chronic granulocytic leukemia. Landmarks in Medical Genetics: Classic Papers with Commentaries. 2004, 132 (51): 103-","journal-title":"Landmarks in Medical Genetics: Classic Papers with Commentaries"},{"issue":"4841 Pt 1","key":"443_CR2","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1126\/science.3422516","volume":"239","author":"SS Clark","year":"1988","unstructured":"Clark SS, McLaughlin J, Timmons M, Pendergast AM, Ben-Neriah Y, Dow LW, Crist W, Rovera G, Smith SD, Witte ON: Expression of a distinctive BCR-ABL oncogene in Ph1-positive acute lymphocytic leukemia (ALL). Science (New York, NY). 1988, 239 (4841 Pt 1): 775-","journal-title":"Science (New York, NY)"},{"issue":"3","key":"443_CR3","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1016\/0092-8674(84)90438-0","volume":"37","author":"JB Konopka","year":"1984","unstructured":"Konopka JB, Watanabe SM, Witte ON: An alteration of the human c-abl protein in K562 leukemia cells unmasks associated tyrosine kinase activity. Cell. 1984, 37 (3): 1035-10.1016\/0092-8674(84)90438-0.","journal-title":"Cell"},{"issue":"51","key":"443_CR4","first-page":"104","volume":"243","author":"JD Rowley","year":"2004","unstructured":"Rowley JD: A new consistent chromosomal adnormality in chronic myelogeneus leukaemia identified by quinacrine fluorescence and Giemsa staining. Landmarks in Medical Genetics: Classic Papers with Commentaries. 2004, 243 (51): 104-","journal-title":"Landmarks in Medical Genetics: Classic Papers with Commentaries"},{"issue":"8","key":"443_CR5","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1182\/blood.V83.8.2038.2038","volume":"83","author":"A Bedi","year":"1994","unstructured":"Bedi A, Zehnbauer BA, Barber JP, Sharkis S, Jones R: Inhibition of apoptosis by BCR-ABL in chronic myeloid leukemia. Blood. 1994, 83 (8): 2038-2044.","journal-title":"Blood"},{"issue":"3","key":"443_CR6","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/sj.onc.1201490","volume":"16","author":"N Cambier","year":"1998","unstructured":"Cambier N, Chopra R, Strasser A, Metcalf D, Elefanty AG: BCR-ABL activates pathways mediating cytokine independence and protection against apoptosis in murine hematopoietic cells in a dose-dependent manner. Oncogene. 1998, 16 (3): 335-10.1038\/sj.onc.1201490.","journal-title":"Oncogene"},{"issue":"12","key":"443_CR7","first-page":"2589","volume":"13","author":"D Cortez","year":"1996","unstructured":"Cortez D, Stoica G, Pierce JH, Pendergast AM: The BCR-ABL tyrosine kinase inhibits apoptosis by activating a Ras-dependent signaling pathway. Oncogene. 1996, 13 (12): 2589-","journal-title":"Oncogene"},{"issue":"2","key":"443_CR8","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1172\/JCI118820","volume":"98","author":"G Bazzoni","year":"1996","unstructured":"Bazzoni G, Carlesso N, Griffin JD, Hemler ME: Bcr\/Abl expression stimulates integrin function in hematopoietic cell lines. J Clin Investig. 1996, 98 (2): 521-10.1172\/JCI118820.","journal-title":"J Clin Investig"},{"issue":"Suppl 1","key":"443_CR9","first-page":"393a","volume":"90","author":"R Zhao","year":"1997","unstructured":"Zhao R, Tarone G, Verfaillie C: Presence of the adhesion inhibitory \u03b21B integrin isoform on CML but not normal progenitors is at least in part responsible for the decreased CML progenitor adhesion. Blood. 1997, 90 (Suppl 1): 393a-","journal-title":"Blood"},{"issue":"4946","key":"443_CR10","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1126\/science.2408149","volume":"247","author":"TG Lugo","year":"1990","unstructured":"Lugo TG, Pendergast A-M, Muller AJ, Witte ON: Tyrosine kinase activity and transformation potency of bcr-abl oncogene products. Science (New York, NY). 1990, 247 (4946): 1079-10.1126\/science.2408149.","journal-title":"Science (New York, NY)"},{"issue":"10","key":"443_CR11","doi-asserted-by":"publisher","first-page":"5531","DOI":"10.1128\/MCB.15.10.5531","volume":"15","author":"D Cortez","year":"1995","unstructured":"Cortez D, Kadlec L, Pendergast AM: Structural and signaling requirements for BCR-ABL-mediated transformation and inhibition of apoptosis. Mol Cell Biol. 1995, 15 (10): 5531-5541.","journal-title":"Mol Cell Biol"},{"issue":"1","key":"443_CR12","first-page":"461","volume":"2009","author":"D Bixby","year":"2009","unstructured":"Bixby D, Talpaz M: Mechanisms of resistance to tyrosine kinase inhibitors in chronic myeloid leukemia and recent therapeutic strategies to overcome resistance. ASH Education Program Book. 2009, 2009 (1): 461-476.","journal-title":"ASH Education Program Book"},{"key":"443_CR13","doi-asserted-by":"publisher","first-page":"S19","DOI":"10.1016\/S0959-8049(02)80599-8","volume":"38","author":"P Manley","year":"2002","unstructured":"Manley P, Cowan-Jacob S, Buchdunger E, Fabbro D, Fendrich G, Furet P, Meyer T, Zimmermann J: Imatinib: a selective tyrosine kinase inhibitor. Eur J Cancer. 2002, 38: S19-S27.","journal-title":"Eur J Cancer"},{"issue":"5","key":"443_CR14","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1016\/j.bmcl.2005.11.042","volume":"16","author":"T Asaki","year":"2006","unstructured":"Asaki T, Sugiyama Y, Hamamoto T, Higashioka M, Umehara M, Naito H, Niwa T: Design and synthesis of 3-substituted benzamide derivatives as Bcr-Abl kinase inhibitors. Bioorg Med Chem Lett. 2006, 16 (5): 1421-1425. 10.1016\/j.bmcl.2005.11.042.","journal-title":"Bioorg Med Chem Lett"},{"issue":"2","key":"443_CR15","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.ceb.2009.01.014","volume":"21","author":"MJ Eck","year":"2009","unstructured":"Eck MJ, Manley PW: The interplay of structural information and functional studies in kinase drug design: insights from BCR-Abl. Curr Opin Cell Biol. 2009, 21 (2): 288-10.1016\/j.ceb.2009.01.014.","journal-title":"Curr Opin Cell Biol"},{"issue":"10","key":"443_CR16","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1016\/j.leukres.2010.04.016","volume":"34","author":"X An","year":"2010","unstructured":"An X, Tiwari AK, Sun Y, Ding P-R, Ashby CR, Chen Z-S: BCR-ABL tyrosine kinase inhibitors in the treatment of Philadelphia chromosome positive chronic myeloid leukemia: a review. Leuk Res. 2010, 34 (10): 1255-1268. 10.1016\/j.leukres.2010.04.016.","journal-title":"Leuk Res"},{"issue":"5","key":"443_CR17","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1016\/j.clinthera.2010.05.003","volume":"32","author":"B Stein","year":"2010","unstructured":"Stein B, Douglas Smith B: Treatment options for patients with chronic myeloid leukemia who are resistant to or unable to tolerate imatinib. Clin Ther. 2010, 32 (5): 804-820. 10.1016\/j.clinthera.2010.05.003.","journal-title":"Clin Ther"},{"issue":"12","key":"443_CR18","doi-asserted-by":"publisher","first-page":"3739","DOI":"10.1182\/blood-2003-12-4276","volume":"104","author":"J Thomas","year":"2004","unstructured":"Thomas J, Wang L, Clark RE, Pirmohamed M: Active transport of imatinib into and out of cells: implications for drug resistance. Blood. 2004, 104 (12): 3739-3745. 10.1182\/blood-2003-12-4276.","journal-title":"Blood"},{"key":"443_CR19","doi-asserted-by":"publisher","first-page":"207","DOI":"10.2147\/CE.S6003","volume":"4","author":"E Jabbour","year":"2009","unstructured":"Jabbour E, Cortes J, Kantarjian H: Nilotinib for the treatment of chronic myeloid leukemia: An evidence-based review. Core evidence. 2009, 4: 207-","journal-title":"Core evidence"},{"issue":"1\u20132","key":"443_CR20","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.bbapap.2005.07.040","volume":"1754","author":"PW Manley","year":"2005","unstructured":"Manley PW, Cowan-Jacob SW, Mestan J: Advances in the structural biology, design and clinical development of Bcr-Abl kinase inhibitors for the treatment of chronic myeloid leukaemia. Biochim Biophys Acta. 2005, 1754 (1\u20132): 3-13.","journal-title":"Biochim Biophys Acta"},{"issue":"19","key":"443_CR21","doi-asserted-by":"publisher","first-page":"6977","DOI":"10.1016\/j.bmc.2010.08.026","volume":"18","author":"PW Manley","year":"2010","unstructured":"Manley PW, Stiefl N, Cowan-Jacob SW, Kaufman S, Mestan J, Wartmann M, Wiesmann M, Woodman R, Gallagher N: Structural resemblances and comparisons of the relative pharmacological properties of imatinib and nilotinib. Bioorg Med Chem. 2010, 18 (19): 6977-6986. 10.1016\/j.bmc.2010.08.026.","journal-title":"Bioorg Med Chem"},{"issue":"2","key":"443_CR22","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.leukres.2009.08.031","volume":"34","author":"M Breccia","year":"2010","unstructured":"Breccia M, Alimena G: Nilotinib: a second-generation tyrosine kinase inhibitor for chronic myeloid leukemia. Leuk Res. 2010, 34 (2): 129-134. 10.1016\/j.leukres.2009.08.031.","journal-title":"Leuk Res"},{"issue":"suppl 6","key":"443_CR23","doi-asserted-by":"crossref","first-page":"vi42","DOI":"10.1093\/annonc\/mdm223","volume":"18","author":"A Olivieri","year":"2007","unstructured":"Olivieri A, Manzione L: Dasatinib: a new step in molecular target therapy. Ann Oncol. 2007, 18 (suppl 6): vi42-vi46.","journal-title":"Ann Oncol"},{"issue":"8","key":"443_CR24","doi-asserted-by":"publisher","first-page":"2532","DOI":"10.1182\/blood-2004-05-1851","volume":"104","author":"T O\u2019Hare","year":"2004","unstructured":"O\u2019Hare T, Pollock R, Stoffregen EP, Keats JA, Abdullah OM, Moseson EM, Rivera VM, Tang H, Metcalf CA, Bohacek RS: Inhibition of wild-type and mutant Bcr-Abl by AP23464, a potent ATP-based oncogenic protein kinase inhibitor: implications for CML. Blood. 2004, 104 (8): 2532-2539. 10.1182\/blood-2004-05-1851.","journal-title":"Blood"},{"issue":"12","key":"443_CR25","doi-asserted-by":"publisher","first-page":"3948","DOI":"10.1182\/blood-2005-06-2209","volume":"106","author":"S Kimura","year":"2005","unstructured":"Kimura S, Naito H, Segawa H, Kuroda J, Yuasa T, Sato K, Yokota A, Kamitsuji Y, Kawata E, Ashihara E: NS-187, a potent and selective dual Bcr-Abl\/Lyn tyrosine kinase inhibitor, is a novel agent for imatinib-resistant leukemia. Blood. 2005, 106 (12): 3948-3954. 10.1182\/blood-2005-06-2209.","journal-title":"Blood"},{"issue":"10","key":"443_CR26","doi-asserted-by":"publisher","first-page":"2712","DOI":"10.1016\/j.bmcl.2007.03.002","volume":"17","author":"T Horio","year":"2007","unstructured":"Horio T, Hamasaki T, Inoue T, Wakayama T, Itou S, Naito H, Asaki T, Hayase H, Niwa T: Structural factors contributing to the Abl\/Lyn dual inhibitory activity of 3-substituted benzamide derivatives. Bioorg Med Chem Lett. 2007, 17 (10): 2712-2717. 10.1016\/j.bmcl.2007.03.002.","journal-title":"Bioorg Med Chem Lett"},{"issue":"3","key":"443_CR27","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1016\/j.bmcl.2007.11.112","volume":"18","author":"M Radi","year":"2008","unstructured":"Radi M, Crespan E, Botta G, Falchi F, Maga G, Manetti F, Corradi V, Mancini M, Santucci MA, Schenone S: Discovery and SAR of 1, 3, 4-thiadiazole derivatives as potent Abl tyrosine kinase inhibitors and cytodifferentiating agents. Bioorg Med Chem Lett. 2008, 18 (3): 1207-1211. 10.1016\/j.bmcl.2007.11.112.","journal-title":"Bioorg Med Chem Lett"},{"issue":"10","key":"443_CR28","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1111\/j.1365-2362.2010.02328.x","volume":"40","author":"P Valent","year":"2010","unstructured":"Valent P: Standard treatment of Ph+ CML in 2010: how, when and where not to use what BCR\/ABL1 kinase inhibitor?. Eur J Clin Investig. 2010, 40 (10): 918-931. 10.1111\/j.1365-2362.2010.02328.x.","journal-title":"Eur J Clin Investig"}],"container-title":["Infectious Agents and Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1750-9378-8-23.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T00:35:43Z","timestamp":1630542943000},"score":1,"resource":{"primary":{"URL":"https:\/\/infectagentscancer.biomedcentral.com\/articles\/10.1186\/1750-9378-8-23"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6,20]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["443"],"URL":"https:\/\/doi.org\/10.1186\/1750-9378-8-23","relation":{},"ISSN":["1750-9378"],"issn-type":[{"value":"1750-9378","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,6,20]]},"assertion":[{"value":"11 April 2013","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2013","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 June 2013","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"23"}}