{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T20:26:42Z","timestamp":1758400002927,"version":"3.37.3"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2019,3,15]],"date-time":"2019-03-15T00:00:00Z","timestamp":1552608000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2019,3,15]],"date-time":"2019-03-15T00:00:00Z","timestamp":1552608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Protein J"],"published-print":{"date-parts":[[2019,4,15]]},"DOI":"10.1007\/s10930-019-09820-z","type":"journal-article","created":{"date-parts":[[2019,3,15]],"date-time":"2019-03-15T23:12:12Z","timestamp":1552691532000},"page":"142-150","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Synergistic Combination Against Chronic Myeloid Leukemia: An Intra-molecular Mechanism of Communication in BCR\u2013ABL1 Resistance"],"prefix":"10.1007","volume":"38","author":[{"given":"Ahmed A.","family":"El Rashedy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Appiah-Kubi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0619-2109","authenticated-orcid":false,"given":"Mahmoud E. S.","family":"Soliman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,3,15]]},"reference":[{"key":"9820_CR1","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1016\/S0140-6736(13)62120-0","volume":"385","author":"JF Apperley","year":"2015","unstructured":"Apperley JF (2015) Chronic myeloid leukaemia. Lancet 385:1447\u20131459. https:\/\/doi.org\/10.1016\/S0140-6736(13)62120-0","journal-title":"Lancet"},{"issue":"Suppl 1","key":"9820_CR2","first-page":"S14","volume":"7","author":"BJ Druker","year":"2001","unstructured":"Druker BJ (2001) Current treatment approaches for chronic myelogenous leukemia. Cancer J 7(Suppl 1):S14\u2013S18","journal-title":"Cancer J"},{"key":"9820_CR3","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/243290a0","volume":"243","author":"JD Rowley","year":"1973","unstructured":"Rowley JD (1973) A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 243:290","journal-title":"Nature"},{"key":"9820_CR4","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1038\/nrc1567","volume":"5","author":"R Ren","year":"2005","unstructured":"Ren R (2005) Mechanisms of BCR\u2013ABL in the pathogenesis of chronic myelogenous leukaemia. Nat Rev Cancer 5:172","journal-title":"Nat Rev Cancer"},{"key":"9820_CR5","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/S0092-8674(05)80094-7","volume":"75","author":"AM Pendergast","year":"1993","unstructured":"Pendergast AM, Quilliam LA, Cripe LD et al (1993) BCR\u2013ABL-induced oncogenesis is mediated by direct interaction with the SH2 domain of the GRB-2 adaptor protein. Cell 75:175\u2013185","journal-title":"Cell"},{"key":"9820_CR6","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1126\/science.3460176","volume":"233","author":"Y Ben-Neriah","year":"1986","unstructured":"Ben-Neriah Y, Daley GQ, Mes-Masson AM et al (1986) The chronic myelogenous leukemia-specific P210 protein is the product of the bcr\/abl hybrid gene. Science 233:212\u2013214","journal-title":"Science"},{"key":"9820_CR7","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1002\/ajh.25011","volume":"93","author":"E Jabbour","year":"2018","unstructured":"Jabbour E, Kantarjian H (2018) Chronic myeloid leukemia: 2018 update on diagnosis, therapy and monitoring. Am J Hematol 93:442\u2013459","journal-title":"Am J Hematol"},{"key":"9820_CR8","doi-asserted-by":"publisher","first-page":"197","DOI":"10.4082\/kjfm.2015.36.5.197","volume":"36","author":"A Granatowicz","year":"2015","unstructured":"Granatowicz A, Piatek CI, Moschiano E et al (2015) An overview and update of chronic myeloid leukemia for primary care physicians. Korean J Fam Med 36:197\u2013202","journal-title":"Korean J Fam Med"},{"key":"9820_CR9","doi-asserted-by":"publisher","first-page":"5443","DOI":"10.1074\/jbc.R112.438382","volume":"288","author":"S Panjarian","year":"2013","unstructured":"Panjarian S, Iacob RE, Chen S et al (2013) Structure and dynamic regulation of Abl kinases. J Biol Chem 288:5443\u20135450. https:\/\/doi.org\/10.1074\/jbc.R112.438382","journal-title":"J Biol Chem"},{"key":"9820_CR10","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/S0092-8674(02)00741-9","volume":"109","author":"M Huse","year":"2002","unstructured":"Huse M, Kuriyan J (2002) The Conformational Plasticity of Protein Kinases. Cell 109:275\u2013282. https:\/\/doi.org\/10.1016\/S0092-8674(02)00741-9","journal-title":"Cell"},{"key":"9820_CR11","first-page":"4236","volume":"62","author":"B Nagar","year":"2002","unstructured":"Nagar B, Bornmann WG, Pellicena P et al (2002) Crystal structures of the kinase domain of c-Abl in complex with the small molecule inhibitors PD173955 and imatinib (STI-571). Cancer Res 62:4236\u20134243","journal-title":"Cancer Res"},{"key":"9820_CR12","doi-asserted-by":"publisher","first-page":"1938","DOI":"10.1126\/science.289.5486.1938","volume":"289","author":"T Schindler","year":"2000","unstructured":"Schindler T, Bornmann W, Pellicena P et al (2000) Structural mechanism for STI-571 inhibition of abelson tyrosine kinase. Science 289:1938\u20131942","journal-title":"Science"},{"key":"9820_CR13","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1038\/nrc2559","volume":"9","author":"J Zhang","year":"2009","unstructured":"Zhang J, Yang PL, Gray NS (2009) Targeting cancer with small molecule kinase inhibitors. Nat Rev Cancer 9:28\u201339. https:\/\/doi.org\/10.1038\/nrc2559","journal-title":"Nat Rev Cancer"},{"key":"9820_CR14","doi-asserted-by":"publisher","first-page":"1518S","DOI":"10.1093\/jn\/137.6.1518S","volume":"137","author":"B Nagar","year":"2007","unstructured":"Nagar B (2007) c-Abl tyrosine kinase and inhibition by the cancer drug imatinib (Gleevec\/STI-571). J Nutr 137:1518S\u20131523S. (discussion 1548S)","journal-title":"J Nutr"},{"key":"9820_CR15","doi-asserted-by":"publisher","first-page":"3123","DOI":"10.1002\/cncr.26679","volume":"118","author":"X Huang","year":"2012","unstructured":"Huang X, Cortes J, Kantarjian H (2012) Estimations of the increasing prevalence and plateau prevalence of chronic myeloid leukemia in the era of tyrosine kinase inhibitor therapy. Cancer 118:3123\u20133127. https:\/\/doi.org\/10.1002\/cncr.26679","journal-title":"Cancer"},{"key":"9820_CR16","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1517\/14728214.2015.1031217","volume":"20","author":"C Fava","year":"2015","unstructured":"Fava C, Morotti A, Dogliotti I et al (2015) Update on emerging treatments for chronic myeloid leukemia. Expert Opin Emerg Drugs 20:183\u2013196","journal-title":"Expert Opin Emerg Drugs"},{"key":"9820_CR17","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1248\/bpb.b15-00103","volume":"38","author":"M Miura","year":"2015","unstructured":"Miura M (2015) Therapeutic drug monitoring of imatinib, nilotinib, and dasatinib for patients with chronic myeloid leukemia. Biol Pharm Bull 38:645\u2013654","journal-title":"Biol Pharm Bull"},{"key":"9820_CR18","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.phrs.2015.10.021","volume":"103","author":"R Roskoski Jr","year":"2016","unstructured":"Roskoski R Jr (2016) Classification of small molecule protein kinase inhibitors based upon the structures of their drug-enzyme complexes. Pharmacol Res 103:26\u201348","journal-title":"Pharmacol Res"},{"key":"9820_CR19","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/S1535-6108(02)00096-X","volume":"2","author":"NP Shah","year":"2002","unstructured":"Shah NP, Nicoll JM, Nagar B et al (2002) Multiple BCR\u2013ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia. Cancer Cell 2:117\u2013125","journal-title":"Cancer Cell"},{"key":"9820_CR20","doi-asserted-by":"publisher","first-page":"8120","DOI":"10.1021\/acs.jmedchem.8b01040","volume":"61","author":"J Schoepfer","year":"2018","unstructured":"Schoepfer J, Jahnke W, Berellini G et al (2018) Discovery of Asciminib (ABL001), an Allosteric Inhibitor of the Tyrosine Kinase Activity of BCR\u2013ABL1. J Med Chem 61:8120\u20138135. https:\/\/doi.org\/10.1021\/acs.jmedchem.8b01040","journal-title":"J Med Chem"},{"key":"9820_CR21","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1038\/nature21702","volume":"543","author":"AA Wylie","year":"2017","unstructured":"Wylie AA, Schoepfer J, Jahnke W et al (2017) The allosteric inhibitor ABL001 enables dual targeting of BCR\u2013ABL1. Nature 543:733\u2013737. https:\/\/doi.org\/10.1038\/nature21702","journal-title":"Nature"},{"key":"9820_CR22","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1182\/blood.V124.21.398.398","volume":"124","author":"A Wylie","year":"2014","unstructured":"Wylie A, Schoepfer J, Berellini G et al (2014) ABL001, a potent allosteric inhibitor of BCR\u2013ABL, prevents emergence of resistant disease when administered in combination with nilotinib in an in vivo murine model of chronic myeloid leukemia. Blood 124:398\u2013398","journal-title":"Blood"},{"key":"9820_CR23","doi-asserted-by":"crossref","first-page":"4841","DOI":"10.1182\/blood.V126.23.4841.4841","volume":"126","author":"LN Eadie","year":"2015","unstructured":"Eadie LN, Saunders VA, Leclercq TM et al (2015) The allosteric inhibitor ABL001 is susceptible to resistance in vitro mediated by overexpression of the drug efflux transporters ABCB1 and ABCG2. Blood 126:4841\u20134841","journal-title":"Blood"},{"key":"9820_CR24","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1182\/blood.V126.23.138.138","volume":"126","author":"OG Ottmann","year":"2015","unstructured":"Ottmann OG, Alimena G, DeAngelo DJ et al (2015) ABL001, a potent, allosteric inhibitor of BCR\u2013ABL, exhibits safety and promising single- agent activity in a phase I study of patients with CML with failure of prior TKI therapy. Blood 126:138\u2013138","journal-title":"Blood"},{"key":"9820_CR25","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1182\/blood-2016-01-694265","volume":"128","author":"TP Hughes","year":"2016","unstructured":"Hughes TP, Goh Y-T, Ottmann OG et al (2016) Expanded phase 1 Study of ABL001, a potent, allosteric inhibitor of BCR\u2013ABL, reveals significant and durable responses in patients with CML-chronic phase with failure of prior TKI therapy. Blood 128:625\u2013625","journal-title":"Blood"},{"key":"9820_CR26","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1056\/NEJM200104053441402","volume":"344","author":"BJ Druker","year":"2001","unstructured":"Druker BJ, Sawyers CL, Kantarjian H et al (2001) Activity of a specific inhibitor of the BCR\u2013ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the philadelphia chromosome. N Engl J Med 344:1038\u20131042. https:\/\/doi.org\/10.1056\/NEJM200104053441402","journal-title":"N Engl J Med"},{"key":"9820_CR27","doi-asserted-by":"publisher","first-page":"3734","DOI":"10.4161\/cc.9.18.13232","volume":"9","author":"AQ Hassan","year":"2010","unstructured":"Hassan AQ, Sharma SV, Warmuth M (2010) Allosteric inhibition of BCR\u2013ABL. Cell Cycle 9:3734\u20133738. https:\/\/doi.org\/10.4161\/cc.9.18.13232","journal-title":"Cell Cycle"},{"key":"9820_CR28","first-page":"1","volume":"47","author":"B Webb","year":"2014","unstructured":"Webb B, Sali A (2014) Protein structure modeling with MODELLER. Protein Struct Predict 47:1\u201315","journal-title":"Protein Struct Predict"},{"key":"9820_CR29","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1002\/jcc.20084","volume":"25","author":"EF Pettersen","year":"2004","unstructured":"Pettersen EF, Goddard TD, Huang CC et al (2004) UCSF Chimera\u2014a visualization system for exploratory research and analysis. J Comput Chem 25:1605\u20131612","journal-title":"J Comput Chem"},{"key":"9820_CR30","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1021\/cr040426m","volume":"106","author":"SA Adcock","year":"2006","unstructured":"Adcock SA, McCammon JA (2006) Molecular dynamics: survey of methods for simulating the activity of proteins. Chem Rev 106:1589\u20131615. https:\/\/doi.org\/10.1021\/cr040426m","journal-title":"Chem Rev"},{"key":"9820_CR31","doi-asserted-by":"publisher","first-page":"1668","DOI":"10.1002\/jcc.20290","volume":"26","author":"DA Case","year":"2005","unstructured":"Case DA, Cheatham TE, Darden T et al (2005) The Amber biomolecular simulation programs. J Comput Chem 26:1668\u20131688. https:\/\/doi.org\/10.1002\/jcc.20290","journal-title":"J Comput Chem"},{"key":"9820_CR32","doi-asserted-by":"publisher","first-page":"14960","DOI":"10.1021\/jp409568h","volume":"117","author":"SK Burger","year":"2013","unstructured":"Burger SK, Schofield J, Ayers PW (2013) Quantum mechanics\/molecular mechanics restrained electrostatic potential fitting. J Phys Chem B 117:14960\u201314966","journal-title":"J Phys Chem B"},{"key":"9820_CR33","doi-asserted-by":"publisher","first-page":"5882","DOI":"10.1021\/acs.jpcb.5b00689","volume":"119","author":"KG Sprenger","year":"2015","unstructured":"Sprenger KG, Jaeger VW, Pfaendtner J (2015) The general AMBER force field (GAFF) can accurately predict thermodynamic and transport properties of many ionic liquids. J Phys Chem B 119:5882\u20135895","journal-title":"J Phys Chem B"},{"key":"9820_CR34","doi-asserted-by":"publisher","first-page":"3172","DOI":"10.1039\/B517914A","volume":"8","author":"Y Shao","year":"2006","unstructured":"Shao Y, Molnar LF, Jung Y et al (2006) Advances in methods and algorithms in a modern quantum chemistry program package. Phys Chem Chem Phys 8:3172\u20133191","journal-title":"Phys Chem Chem Phys"},{"key":"9820_CR35","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1063\/1.445869","volume":"79","author":"WL Jorgensen","year":"1983","unstructured":"Jorgensen WL, Chandrasekhar J, Madura JD et al (1983) Comparison of simple potential functions for simulating liquid water. J Chem Phys 79:926\u2013935. https:\/\/doi.org\/10.1063\/1.445869","journal-title":"J Chem Phys"},{"key":"9820_CR36","doi-asserted-by":"publisher","first-page":"3084","DOI":"10.1021\/ct400341p","volume":"9","author":"DR Roe","year":"2013","unstructured":"Roe DR, Cheatham TE (2013) PTRAJ and CPPTRAJ: Software for Processing and Analysis of Molecular Dynamics Trajectory Data. J Chem Theory Comput 9:3084\u20133095","journal-title":"J Chem Theory Comput"},{"key":"9820_CR37","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1021\/ci500161d","volume":"54","author":"E Seifert","year":"2014","unstructured":"Seifert E (2014) OriginPro 9.1: Scientific data analysis and graphing software\u2014Software review. J Chem Inf Model 54:1552\u20131552. https:\/\/doi.org\/10.1021\/ci500161d","journal-title":"J Chem Inf Model"},{"key":"9820_CR38","doi-asserted-by":"publisher","first-page":"2626","DOI":"10.1021\/ci4002475","volume":"53","author":"M Ylilauri","year":"2013","unstructured":"Ylilauri M, Pentik\u00e4inen OT (2013) MMGBSA as a tool to understand the binding affinities of filamin-peptide interactions. J Chem Inf Model 53:2626\u20132633. https:\/\/doi.org\/10.1021\/ci4002475","journal-title":"J Chem Inf Model"},{"key":"9820_CR39","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1021\/ci100275a","volume":"51","author":"T Hou","year":"2011","unstructured":"Hou T, Wang J, Li Y, Wang W (2011) Assessing the performance of the MM\/PBSA and MM\/GBSA methods. 1. The accuracy of binding free energy calculations based on molecular dynamics simulations. J Chem Inf Model 51:69\u201382. https:\/\/doi.org\/10.1021\/ci100275a","journal-title":"J Chem Inf Model"},{"key":"9820_CR40","doi-asserted-by":"publisher","DOI":"10.5772\/37107","author":"JM Hayes","year":"2011","unstructured":"Hayes JM, Archontis G (2011) MM-GB (PB) SA calculations of protein-ligand binding free energies. InTech. https:\/\/doi.org\/10.5772\/37107","journal-title":"InTech"},{"key":"9820_CR41","doi-asserted-by":"publisher","first-page":"70681","DOI":"10.1371\/journal.pone.0070681","volume":"8","author":"L Pan","year":"2013","unstructured":"Pan L, Patterson JC, Deshpande A et al (2013) Molecular dynamics study of Zn(A\u03b2) and Zn(A\u03b2)2. PLoS ONE 8:70681\u201370688. https:\/\/doi.org\/10.1371\/journal.pone.0070681","journal-title":"PLoS ONE"},{"key":"9820_CR42","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1080\/15216540500138246","volume":"57","author":"G Wijffels","year":"2005","unstructured":"Wijffels G, Dalrymple B, Kongsuwan K, Dixon N (2005) Conservation of eubacterial replicases. IUBMB Life 57:413\u2013419. https:\/\/doi.org\/10.1080\/15216540500138246","journal-title":"IUBMB Life"},{"key":"9820_CR43","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/0022-2836(84)90231-6","volume":"178","author":"TJ Richmond","year":"1984","unstructured":"Richmond TJ (1984) Solvent accessible surface area and excluded volume in proteins. Analytical equations for overlapping spheres and implications for the hydrophobic effect. J Mol Biol 178:63\u201389","journal-title":"J Mol Biol"}],"container-title":["The Protein Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10930-019-09820-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10930-019-09820-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10930-019-09820-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T00:23:16Z","timestamp":1667521396000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10930-019-09820-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,15]]},"references-count":43,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,4,15]]}},"alternative-id":["9820"],"URL":"https:\/\/doi.org\/10.1007\/s10930-019-09820-z","relation":{},"ISSN":["1572-3887","1875-8355"],"issn-type":[{"type":"print","value":"1572-3887"},{"type":"electronic","value":"1875-8355"}],"subject":[],"published":{"date-parts":[[2019,3,15]]},"assertion":[{"value":"15 March 2019","order":1,"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 conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}