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A history of cancer chemotherapy. Cancer Res.<\/i>, 68<\/b>, 8643\u20138653 (2008).","DOI":"10.1158\/0008-5472.CAN-07-6611"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2) Sawyers C. Targeted cancer therapy. Nature<\/i>, 432<\/b>, 294\u2013297 (2004).","DOI":"10.1038\/nature03095"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3) Capdeville R, Buchdunger E, Zimmermann J, Matter A. Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug. Nat. Rev. Drug Discov.<\/i>, 1<\/b>, 493\u2013502 (2002).","DOI":"10.1038\/nrd839"},{"key":"4","unstructured":"4) Iqbal N, Iqbal N. Imatinib: a breakthrough of targeted therapy in cancer. Chemother. Res. Pract.<\/i>, 2014<\/b>, 357027 (2014)."},{"key":"5","unstructured":"5) Manley PW, Cowan-Jacob SW, Buchdunger E, Fabbro D, Fendrich G, Furet P, Meyer T, Zimmermann J. Imatinib: a selective tyrosine kinase inhibitor. Eur. J. Cancer<\/i>, 38<\/b> (Suppl. 5), 19\u201327 (2002)."},{"key":"6","doi-asserted-by":"crossref","unstructured":"6) Lambert GK, Duhme-Klair AK, Morgan T, Ramjee MK. The background, discovery and clinical development of BCR-ABL inhibitors. Drug Discov. Today<\/i>, 18<\/b>, 992\u20131000 (2013).","DOI":"10.1016\/j.drudis.2013.06.001"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7) Sherbenou DW, Druker BJ. Applying the discovery of the Philadelphia chromosome. J. Clin. Invest.<\/i>, 117<\/b>, 2067\u20132074 (2007).","DOI":"10.1172\/JCI31988"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8) Sirvent A, Benistant C, Roche S. Cytoplasmic signalling by the c-Abl tyrosine kinase in normal and cancer cells. Biol. Cell<\/i>, 100<\/b>, 617\u2013631 (2008).","DOI":"10.1042\/BC20080020"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9) Gorre ME, Mohammed M, Ellwood K, Hsu N, Paquette R, Rao PN, Sawyers CL. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science<\/i>, 293<\/b>, 876\u2013880 (2001).","DOI":"10.1126\/science.1062538"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10) Melo JV, Chuah C. Resistance to imatinib mesylate in chronic myeloid leukaemia. Cancer Lett.<\/i>, 249<\/b>, 121\u2013132 (2007).","DOI":"10.1016\/j.canlet.2006.07.010"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11) Hochhaus A, O\u2019Brien SG, Guilhot F, Druker BJ, Branford S, Foroni L, Goldman JM, Muller MC, Radich JP, Rudoltz M, Mone M, Gathmann I, Hughes TP, Larson RA, IRIS Investigators. Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia<\/i>, 23<\/b>, 1054\u20131061 (2009).","DOI":"10.1038\/leu.2009.38"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Weisberg E, Manley PW, Cowan-Jacob SW, Hochhaus A, Griffin JD. Second generation inhibitors of BCR-ABL for the treatment of imatinib-resistant chronic myeloid leukaemia. Nat. Rev. Cancer<\/i>, 7<\/b>, 345\u2013356 (2007).","DOI":"10.1038\/nrc2126"},{"key":"13","unstructured":"13) Bitencourt R, Zalcberg I, Louro ID. Imatinib resistance: a review of alternative inhibitors in chronic myeloid leukemia. Rev. Bras. Hematol. Hemoter.<\/i>, 33<\/b>, 470\u2013475 (2011)."},{"key":"14","unstructured":"14) Valent P. Imatinib-resistant chronic myeloid leukemia (CML): Current concepts on pathogenesis and new emerging pharmacologic approaches. Biologics<\/i>, 1<\/b>, 433\u2013448 (2007)."},{"key":"15","unstructured":"15) Quintas-Cardama A, Kantarjian H, Cortes J. Flying under the radar: the new wave of BCR-ABL inhibitors. Nat. Rev. Drug Discov.<\/i>, 6<\/b>, 834\u2013848 (2007)."},{"key":"16","unstructured":"16) An X, Tiwari AK, Sun Y, Ding PR, Ashby CR Jr, Chen ZS. BCR-ABL tyrosine kinase inhibitors in the treatment of Philadelphia chromosome positive chronic myeloid leukemia: a review. Leuk. Res.<\/i>, 34<\/b>, 1255\u20131268 (2010)."},{"key":"17","doi-asserted-by":"crossref","unstructured":"17) Dzubak P, Hajduch M, Vydra D, Hustova A, Kvasnica M, Biedermann D, Markova L, Urban M, Sarek J. Pharmacological activities of natural triterpenoids and their therapeutic implications. Nat. Prod. Rep.<\/i>, 23<\/b>, 394\u2013411 (2006).","DOI":"10.1039\/b515312n"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18) Radwan MO, Ismail MAH, El-Mekkawy S, Ismail NSM, Hanna AG. Synthesis and biological activity of new 18\u03b2-glycyrrhetinic acid derivatives. Arab. J. Chem.<\/i>, 9<\/b>, 390\u2013399 (2016).","DOI":"10.1016\/j.arabjc.2013.06.032"},{"key":"19","unstructured":"19) Holl\u00f3sy F, Meszaros G, Bokonyi G, Idei M, Seprodi A, Szende B, Keri G. Cytostatic, cytotoxic and protein tyrosine kinase inhibitory activity of ursolic acid in A431 human tumor cells. Anticancer Res.<\/i>, 20<\/b> (6B), 4563\u20134570 (2000)."},{"key":"20","doi-asserted-by":"crossref","unstructured":"20) Zhou BN, Johnson RK, Mattern MR, Fisher PW, Kingston DG. The first naturally occurring Tie2 kinase inhibitor. Org. Lett.<\/i>, 3<\/b>, 4047\u20134049 (2001).","DOI":"10.1021\/ol016775+"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21) Emirda\u011f-\u00d6zt\u00fcrk S, Babahan I, Ozmen A. Synthesis, characterization and in vitro<\/i> anti-neoplastic activity of gypsogenin derivatives. Bioorg. Chem.<\/i>, 53<\/b>, 15\u201323 (2014).","DOI":"10.1016\/j.bioorg.2013.12.001"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22) Arslan I, Celik A, Melzig MF. Nebulosides A-B, novel triterpene saponins from under-ground parts of Gypsophila arrostii<\/i> Guss. var. nebulosa. Bioorg. Med. Chem.<\/i>, 21<\/b>, 1279\u20131283 (2013).","DOI":"10.1016\/j.bmc.2012.12.036"},{"key":"23","unstructured":"23) Henry M. Saponins and phylogeny: Example of the \u201cgypsogenin group\u201d saponins. Phytochem. Rev.<\/i>, 4<\/b>, 89\u201394 (2005)."},{"key":"24","unstructured":"24) Xie LX, Sun DF, Wang HY, Yao QQ, Sun JY. Research progress on chemical constituents in plants of Gypsophila L. and their pharmacological activities. Zhong. Cao. Yao.<\/i>, 46<\/b>, 280\u2013292 (2015)."},{"key":"25","doi-asserted-by":"crossref","unstructured":"25) Emirda\u011f-\u00d6zt\u00fcrk S, Karayildirim T, Capci-Karagoz A, Alankus-Caliskan O, Ozmen A, Poyrazoglu-Coban E. Synthesis, antimicrobial and cytotoxic activities, and structure\u2013activity relationships of gypsogenin derivatives against human cancer cells. Eur. J. Med. Chem.<\/i>, 82<\/b>, 565\u2013573 (2014).","DOI":"10.1016\/j.ejmech.2014.05.084"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26) Klein E, Ben-Bassat H, Neumann H, Ralph P, Zeuthen J, Polliack A, Vanky F. Properties of the K562 cell line, derived from a patient with chronic myeloid leukemia. Int. J. Cancer<\/i>, 18<\/b>, 421\u2013431 (1976).","DOI":"10.1002\/ijc.2910180405"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27) Karabacak M, Altintop MD, Ibrahim Ciftci H, Koga R, Otsuka M, Fujita M, Ozdemir A. Synthesis and evaluation of new pyrazoline derivatives as potential anticancer agents. Molecules<\/i>, 20<\/b>, 19066\u201319084 (2015).","DOI":"10.3390\/molecules201019066"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28) Ali TF, Iwamaru K, Ciftci HI, Koga R, Matsumoto M, Oba Y, Kurosaki H, Fujita M, Okamoto Y, Umezawa K, Nakao M, Hide T, Makino K, Kuratsu J, Abdel-Aziz M, Abuo-Rahma Gel D, Beshr EA, Otsuka M. 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Contribution of BCR-ABL-independent activation of ERK1\/2 to acquired imatinib resistance in K562 chronic myeloid leukemia cells. Cancer Sci.<\/i>, 101<\/b>, 137\u2013142 (2010).","DOI":"10.1111\/j.1349-7006.2009.01365.x"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34) Ma L, Shan Y, Bai R, Xue L, Eide CA, Ou J, Zhu LJ, Hutchinson L, Cerny J, Khoury HJ, Sheng Z, Druker BJ, Li S, Green MR. A therapeutically targetable mechanism of BCR-ABL-independent imatinib resistance in chronic myeloid leukemia. Sci. Transl. Med.<\/i>, 6<\/b>, 252ra121 (2014).","DOI":"10.1126\/scitranslmed.3009073"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35) Airiau K, Turcq B, Mahon FX, Belloc F. A new mechanism of resistance to ABL1 tyrosine kinase inhibitors in a BCR-ABL1-positive cell line. Leuk. Res.<\/i>, 61<\/b>, 44\u201352 (2017).","DOI":"10.1016\/j.leukres.2017.08.014"},{"key":"36","doi-asserted-by":"crossref","unstructured":"36) O\u2019Hare T, Eide CA, Deininger MWN. Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia. Blood<\/i>, 110<\/b>, 2242\u20132249 (2007).","DOI":"10.1182\/blood-2007-03-066936"},{"key":"37","unstructured":"37) Soverini S, Hochhaus A, Nicolini FE, Gruber F, Lange T, Saglio G, Pane F, M\u00fcller MC, Ernst T, Rosti G, Porkka K, Baccarani M, Cross NCP, Martinelli G. BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhbitors: recommendations from an expert panel on behalf of European LeukemiaNet. Blood<\/i>, 118<\/b>, 1208\u20131215 (2011)."},{"key":"38","doi-asserted-by":"crossref","unstructured":"38) Kitagawa D, Yokota K, Gouda M, Narumi Y, Ohmoto H, Nishiwaki E, Akita K, Kirii Y. Activity-based kinase profiling of approved tyrosine kinase inhibitors. 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