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xp_Complete_Ac_29273.pride.mztab.gzftp://ftp.pride.ebi.ac.uk/pride/data/archive/2014/06/PXD000216/PRIDE_Exp_Complete_Ac_29270.pride.mztab.gzprimaryOK200003770Pieter-Jan De BockMass SpectrometryBottom-up proteomicsunknown unknownHumanImatinibK562Lc-msmsLong columnsSilachttp://www.ebi.ac.uk/pride/archive/projects/PXD000216Not availablePrideNot available6x(13)C labeled residuemonohydroxylated residuemono N-acetylated residue2-pyrrolidone-5-carboxylic acid (Gln)Not availableProteomicsLTQ Orbitrapinstrument modelCOMPLETEHomo Sapiens (human)Not availablepieter-jan.debock@cea.frBiomedicalBiochemistry10.6019/PXD000216377Not Available, Unavailable.leukemia, BCR-ABL Positive chronic myelogenous leukemia, human being, chronic myelocytic leukemia, total expressed protein, 4-(4-METHYL-PIPERAZIN-1-YLMETHYL)-N-[4-METHYL-3-(4-PYRIDIN-3-YL-PYRIMIDIN-2-YLAMINO)-PHENYL]-BENZAMIDE, BCR-ABL1 positive, chronic granulocytic leukaemia, K-562, chronic myeloid leukemia, somatic, chronic myelogenous leukemias, Philadelphia chromosome-positive, chronic, alpha-(4-methyl-1-piperazinyl)-3'-((4-(3-pyridyl)-2-pyrimidinyl)amino)-p-toluidide, CML, K562, hematopoeitic - chronic myelocytic leukaemia (CML), chronic myelogenous, STI 571, imatinib, chronic myelogenous leukemia, BCR-ABL1 Positive, resistant to imatinib, Cell., 4-[(4-methylpiperazin-1-yl)methyl]-N-{4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl}benzamide, atypical, K.562, RCB0027, chronic myelocytic leukaemia, CML - chronic myelogenous leukaemia, GM05372E, myeloid leukemia, hematopoeitic - chronic myelocytic leukemia (CML), K562 cell, chronic myeloid, K-562 cell, Somatic mutation, Philadelphia chromosome positive, CML - chronic myelogenous leukemia, BCR-ABL Positive chronic myelogenous leukaemia, chronic myelogenous leukemia (CML), man, human, KO, chronic granulocytic leukemia, K 562, chronic myelogenous leukaemia, CML - chronic Myelogenous Leukemia, chronic myeloid leukaemia, Myeloid Leukemia, chronic myelogenous leukaemia (CML), RCB1897, Proteomes, GM05372Not Available, Unavailable.v-abl, para Tyrosine, DIMETHYL SULFOXIDE, Raw, Lysine Hydrochloride, Polypeptides, protein polypeptide chains, chronic myelogenous, L-glutamine, Lysine Acetate, C-abl, Drug Tolerance, BCR-ABL1 Positive, p150, BCR, L-2-aminoglutaramic acid, 2, CG40494, JTK7, Kinase, Analysis, myd, WMS, L Lysine, C79691, (S)-2-amino-5-guanidinopentanoic acid, F, amino acids, AI325092, Abl, Analyses, ABL, K, anabolism, M, 2-amino-3-(4-hydroxyphenyl)propanoic acid, 3-(p-Hydroxyphenyl)alanine, Q, R, dimethyl sulphoxide, Mbp-1, Arginine, Kitl, proteins, Monohydrate DL-Arginine Acetate, Y, Mast cell growth factor, Lccp, AI853148, LYS, column, medicine, abl, Lysin, adult chronic leukemia, Homo sapiens disease, stage, ATP Phosphotransferases, drug tolerance, Dimethylsulfoxid, SGS, DMSO, dmso, immune system tolerance, acetylation, D-Abl, somatomedin, arginine, para-Tyrosine, IBP1, Spectrum Analysis, alpha-amino carboxylic acids, ACMICD, Imatinib, STI571, (CH3)2SO, imatinib, mKIAA0609, Methionin, methionine, D-abl, Hmet, DmelCG4032, Hydrogen Oxide, AI561783, fg, Acid, 4674, Amino acids, MTP deficiency, Stem cell factor, CML - chronic myelogenous leukemia, expanded, Spectrometry, MASCOT, chronic myelogenous leukemia (CML), alpha, STAT5, (S)-2, human, L isomer, MDC1D, stem cell factor, abetalipoproteinemia, Self Tolerance, enr, Gleevec, CML - chronic Myelogenous Leukemia, Cells, chronic myelogenous leukaemia (CML), L-Tyrosine, Acids, CGP57148, Liquimeth, Gb, Comparative Studies, big, CLL, GLUTAMINE, Clo, 2-amino-4-(methylsulfanyl)butanoic acid, abl1, False, Slf, SLF, SK23-mel, developmental stage, 5133400C09Rik, Levoglutamide, dimethylsulfoxyde, biosynthesis, precursor, Isotope-Coded Affinity, protein-containing complex, Philadelphia chromosome-positive, l(3)04674, CML, large, cAbl, Bassen-Kornzweig syndrome, CGP 57148, disease or disorder, congenital betalipoprotein deficiency syndrome, atypical, Lysine, Isotopically-Coded Affinity, DmelCG40494, sulfinylbis(methane), dAbl, imatinib mesylate, MDDGB6, (2S)-2, Somatic mutation, PHL, Abl1, man, microsomal triglyceride transfer Protein deficiency, synthesis, mKIAA0989, dimetil sulfoxido, Con, drugs, 2-amino-4-(methylthio)butanoic acid, Mesylate, blz, L-Arg, peptidos, Tyrosin, Imatinib Methanesulfonate, metionina, 4-[(4-methylpiperazin-1-yl)methyl]-N-{4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl}benzamide methanesulfonate, AblK, leukemia, ALL, Betalipoprotein deficiency disease, Dabl, c-abl, ST 1571, hematopoietic growth factor KL, chronic leukemia (disease), disorders, BCR-ABL1 positive, alpha-amino acids, DAbl, L-Isomer, chronic, Cell, polypeptide, K562, hematopoeitic - chronic myelocytic leukaemia (CML), STI 571, native protein, Immune Tolerance, chronic myelogenous leukemia, tirosina, L-Isomer Arginine, Stable Isotope, Acetate, Glutamic acid 5-amide, condition, MFS1, L-Lysine, Mass Spectrum Analyses, Met, Xcml, Col4a-1, Glutamic acid amide, (2S)-2-amino-5-guanidinopentanoic acid, bcr|abl, dimethyl sulfoxide, Isotope Labeling, Isotopically-Coded, plan specification, chronic myelogenous leukaemia, MGF, Mgf, chronic myeloid leukaemia, abetalipoproteinemia neuropathy, Enisyl, Immunological Tolerance, Bru, BCR-ABL Positive chronic myelogenous leukemia, Ableson, single-organism developmental process, L-arginine, DL-Arginine Acetate, Aminosaeure, apolipoprotein B deficiency, Bassen Kornzweig syndrome, Somatomedin-C, Mbp1, cleavage, Amino acid, Methanesulfonate, 4-(4-METHYL-PIPERAZIN-1-YLMETHYL)-N-[4-METHYL-3-(4-PYRIDIN-3-YL-PYRIMIDIN-2-YLAMINO)-PHENYL]-BENZAMIDE, Monohydrate, protein, acanthocytosis, contrasted, L-(+)-glutamine, peptide, L-Isomer Methionine, L-Glutaminsaeure-5-amid, Methionine, ClvPrd, peptido, diseases, diseases and disorders, Arg, protein aggregate, chronic myelocytic leukaemia, Isotopically-Coded Affinity Tagging, multicellular organismal biosynthetic process, BCR1, myeloid leukemia, Mass Spectrum Analysis, Svc, single-organism biosynthetic process, human disease, peptides, D-Glutamine, (S)-2-Amino-5-guanidinovaleric acid, BCR-ABL Positive chronic myelogenous leukaemia, somatomedin-C, SF, epsilon-diaminocaproic acid, Glivec, adult chronic leukaemia, c-ABL, c-Abl, CG4032, IGF1, Tyr, ppm, Mechano growth factor, Soluble KIT ligand, leukemia (disease), Tagging, Sl, GPHYSD2, Racemethionine, Stable Isotope Labeling, ATP, L-Arginin, IGF-I, steel factor, chronic myelocytic leukemia, dimethyli sulfoxidum, gyltl1b-b, Am ABL, Aminokarbonsaeure, methylsulfinylmethane, 2-Amino-3-(p-hydroxyphenyl)propionic acid, 2-Amino-4-(methylthio)butyric acid, Arginine Hydrochloride, late, somatic, STI-571, imatinib mesilate, results, sKITLG, Tyrosine, Spectroscopy, D22S662, MDDGA6, mechano growth factor, Diseases, lysine, Immunologic Tolerance, resistant to imatinib, 4-[(4-methylpiperazin-1-yl)methyl]-N-{4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl}benzamide, D-ash, Igf-1, fixed, tyrosine, L Glutamine, parent ion, L-Arginine, bcr/abl, Amino Acid, Transphosphorylases, Epistemology, SHEP7, (methanesulfinyl)methane, gyltl1b, mast cell growth factor, L-isomer, mdc1d, MASS, CG17960, leukaemia (disease), L-glutamic acid gamma-amide, imatinib., Dsrc7, disease, Kitlg, chronic granulocytic leukemia, KL-1, precursor ion, Tolerance, enlarged, CGP-57148, KITLG, Polypeptide, Protein Kinase, Alpha-(4-methyl-1-piperazinyl)-3'-((4-(3-pyridyl)-2-pyrimidinyl)amino)-p-tolu-p-toluidide, Proteomes, Dmel_CG00000, other disease, human being, AW549739, 5-diamino-5-oxopentanoic acid, Aminocarbonsaeure, L Isomer, FBN, FPH2, chronic granulocytic leukaemia, Spectrum Analyses, alpha-amino acid, chronic myeloid leukemia, (2S)-2-amino-4-carbamoylbutanoic acid, chronic myelogenous leukemias, froggy, Gyltl1a, L-(+)-arginine, method, CG17617, polypeptide chain, (2S)-2-amino-5-(carbamimidamido)pentanoic acid, ECTOL1, imatinib methansulfonate, method used in an experiment, resistance, Mass, L-Methionine, rhoGAP1A, Del(8)44H, imatinib monomesylate, Phosphotransferase, Pedameth, Mass Spectroscopy, S(O)Me2, study, chronic myeloid, formation, chronic leukemia, D22S11, Philadelphia chromosome positive, Acetylations, EG:23E12.5, Transphosphorylase, ATP-protein phosphotransferase, EG:23E12.2, non-neoplastic, OCTD, BPFD#36, 10^[-6], L Tyrosine, Stable, great, Myeloid Leukemia, Isotope-Coded Affinity Tagging, disorder, L-Glutamine, E430008G22Rik, familial hypobetalipoproteinemia, data, ST1571, DL-Methionine, protein complex, synthesize, Dash, total expressed protein, l(3)73Ba, medical condition, L-2-Aminoglutaramic acid, DL Arginine Acetate, homozygous familial hypobetalipoproteinemia, Labeling, Phosphotransferases, Peptide, alpha-(4-methyl-1-piperazinyl)-3'-((4-(3-pyridyl)-2-pyrimidinyl)amino)-p-toluidide, development, Isotope, CGP57148B, natural protein, Protein, CG40453, Hydrochloride, L Arginine, L-Glutamin, Dimethyl sulfoxide, CML - chronic myelogenous leukaemia, chronic leukaemia (disease), Bassen-Kornzweig disease, Isotope Coded Affinity Tagging, WMS2, hematopoeitic - chronic myelocytic leukemia (CML), Mass Spectrum, l(3)c-abl, Kinases, cml-A, Amino, Affinity Tagging, Ddash/abl, D Glutamine, c-Kit ligand, SSKS, DROTKABL3, alpha-amino-gamma-methylmercaptobutyric acid, Isotope-Coded, Peptid, microsomal triglyceride transfer protein deficiency disease, mKIAA3017, SCF, c-ABL1, variable, dimethyl sulfur oxide, 6-diaminohexanoic acid0trueProteome Changes Induced by Imatinib and Novel Imatinib Derivatives in K562 Human Chronic Myeloid Leukemia CellsInhibition of deregulated protein kinases by small molecule drugs has evolved into a major therapeutic strategy for the treatment of human malignancies. Imatinib mesylate has emerged as the leading compound to treat chronic myeloid leukemia (CML), through its inhibition of Bcr- Abl tyrosine kinases, and other cancers. However, resistance to imatinib develops frequently, particularly in late-stage disease and has necessitated the development of new BCR-ABL inhibitors. The synthesis of a new series of phenylaminopyrimidines, structurally related to imatinib showed large interest since the introduction of the nilotibin. To identify the cellular pathways affected by new synthesized compounds, we applied mass spectrometry together with stable isotope labeling by amino acids in cell culture (SILAC) for the comparative study of protein expression in K562 cells that were untreated or treated with imatinib and imatinib derivates. Further, the global proteome of the K562 cells treated with imatinib were quantitatively compared with the cells treated with the new compounds. This study enriched our knowledge about direct cellular targets of kinase selective drugs. Further the results offered important new knowledge for gaining insights into the structural effects of action of the new compounds. Samples were analyzed on a longer column (30cm) and a longer gradient (180min). Raw data files were processed with Mascot distiller 2.3. The mgf files were searched with Mascot daemon 2.3. The quantification was also done by Mascot Distiller. All data was stored in ms_lims. The manual validation of false peptide ratios was done with Rover (part of ms_lims). Fixed modifications: none. Variable modifications: acetylation of peptide N-terminus, pyroglutamate formation of N-terminal glutamine, methionine oxidation. Enzyme: trypsine with one missed cleavage allowed. Precursor mass tolerance: 10 ppm. Peptide fragment mass tolerance: 0.5 Da Quantitation method: SILAC arginine and lysine +6 Da. Overview of the 17 different analyses: B SK23 vs DMSO C Y22 vs DMSO D SK20 vs DMSO E Y18 vs DMSO I SK20 vs DMSO K Y18 vs DMSO O Y22 vs DMSO R Imatinib vs Water Z Imatinib vs Water J SK20 vs Imatinib M SK23 vs Imatinib N Y22 vs Imatinib P SK23 vs Imatinib Q Y18 vs Imatinib S Y22 vs Imatinib T SK20 vs Imatinib Y Y18 vs Imatinib2014-06-302013-04-18PXD0002164454464152446644991755825805931173880433309286643235929535883906288705108061119459932716024619624619716032933206375811363399981036358945327583851187947398007NCBITaxon:12805723071351225117750585557146835167971836491673871349215891030629159291583641515849388580332715910022638886915135588475187043511232949309451464796928123977133216413328038103430436548135833398580818894621432059179392118259028788929502714936329579069026373717493469381247818662725632273219286728139545132949112471904007274081691804541619345374571390363453011431140206411981087135547714245073264422953321043555127443214967142831666943694559729100392375146157546478422422089641392317447127013901143193382935508230741114811946694896935293725264999712646904106617275802405507216599366581216595214053294128213312832965431282128033952321832171843183292043531522246281124543575547874980195759284593307972536231706671436733115955644421432138184922394882426191454813112404791096976NCBITaxon:21572261551531117957334720596879866233098005888455862652818178081736309431796989361604885661409859454745664162425678251187023175131187053204963035554320465650506326331299NCBITaxon:131345658606886076993894246887955453512014887519795921612962141410016023587002642032890969456941016763410210762285316435186763185431100291187002157457744491760445246794144242324113NCBITaxon:177321409292979310239101178709NCBITaxon:405597499079913278839652611227349821717018736745498216101161035856915693132842626587249821110360983341392696133679535889108944866330315819NCBITaxon:4932992530688391000589873299404458611535711471612249113430531156312017126375543039114155421932993512993872631787236669872464261513458872742157267872862354762422314146862111510416079129831530554689111800665564841255228562198822136162997677633631689825102169982313288811174673897641167610807723264241155786184468944447415367767446859600393765209611822635735784582730688086377216632666898626NCBITaxon:2697049339862410312NCBITaxon:138983819201124136810893161009975961286445464148643307731974794640986099586522832917619662776689605960615729513722144670171101256737863912334353354810523110090405449317998686553878386544306154703342491042986357884019373349615508771198215973975749870878229719721540782119085707520618998507648025631841898571587762395165586588622381902649464546352864076746360NCBITaxon:110719646375939288357461287460113450664912538458814594319722196381116752638588596NCBITaxon:61574084408797787237953496794408126322690038039452641145953612351786169407722724323074691123869869597854096409795418694NCBITaxon:220030895442432778697627912924970361240905180426430409286924093200302747679274596153284812313625426428257313150475269796102993886599034694171344338626347515415540363299796628773239644042628993062186441954866331495755846282382352286287173623196693994636010688420436010439947968583558595932184799689544404696811260710173294118696141633316780781440772118694NCBITaxon:6191118698840231719118691931281183610036105023185579969484851908021878783749907038476641004116922595534706345910659212257862607046183260705334542260707NCBITaxon:780NCBITaxon:15024515166584578853187029442712115869103716478496209285747078124966842528619212638541094343197504457NCBITaxon:10357383379192875NCBITaxon:10359NCBITaxon:714282927263412680639560295987044830064180224275226643731055524235443159084122430814336122823344690081502575412983964271191364516996328104121697927262327262430085212389936436801097791356223347471821314269704958331361858030NCBITaxon:56938268830640297605277963818583342409061147787127441415368163940674588858130767494029554622432640817212816140559204254687613837081274423434271408170285099011912744201274426519534911370249240543734131641660817562615282352567506033376028532189517731193501846451450511492412153239564818822996731709158002571256148015490313847360338481423166385962859631015101450520493227591428693732664179332648373153NCBITaxon:961529722109767714126220029811211144937608333419110792762833325186610065812375612666255559292484791486917749200360094917226175661435340731203258352472259447517503754513678303983649908515151438992NCBITaxon:1155237453747