115354PathwayDasatinib Inhibition of BCR-ABL Dasatinib is a tyrosine kinase inhibitor used to treat chronic myelogenous leukemia (CML), a cancer characterized by increased and unregulated growth of white blood cells in the bone marrow and the accumulation of these cells in the blood and acute lymphoblastic leukemia . The cause of CML pathophysiology is the BCR-ABL fusion protein - the result of a genetic abnormality known as the Philadelphia chromosome in which Abelson Murine Leukemia viral oncogene homolog 1 (ABL1) translocates within the Breakpoint Cluster Region (BCR) gene on chromosome 22. BCR-ABL is a cytoplasm-targeted constitutively active tyrosine kinase that activates several oncogenic pathways which promote increased cell proliferation and survival including the MAPK/ERK Pathway, the JAK-STAT Pathway, and the PI3K/Akt pathway. For greater detail, refer to the pathway titled BCR-ABL Action in CML Pathogenesis. Dasatinib is able to bind ABL with greater affinity than Imatinib (25-55 times more potent). It is therefore administered to patients with Imatinib resistance.
Drug ActionPW124513CenterPathwayVisualizationContext12478923502500#000099PathwayVisualization115217115354Dasatinib Inhibition of BCR-ABL Dasatinib is a tyrosine kinase inhibitor used to treat chronic myelogenous leukemia (CML), a cancer characterized by increased and unregulated growth of white blood cells in the bone marrow and the accumulation of these cells in the blood and acute lymphoblastic leukemia . The cause of CML pathophysiology is the BCR-ABL fusion protein - the result of a genetic abnormality known as the Philadelphia chromosome in which Abelson Murine Leukemia viral oncogene homolog 1 (ABL1) translocates within the Breakpoint Cluster Region (BCR) gene on chromosome 22. BCR-ABL is a cytoplasm-targeted constitutively active tyrosine kinase that activates several oncogenic pathways which promote increased cell proliferation and survival including the MAPK/ERK Pathway, the JAK-STAT Pathway, and the PI3K/Akt pathway. For greater detail, refer to the pathway titled BCR-ABL Action in CML Pathogenesis. Dasatinib is able to bind ABL with greater affinity than Imatinib (25-55 times more potent). It is therefore administered to patients with Imatinib resistance.
Drug133602932289275Braun TP, Eide CA, Druker BJ: Response and Resistance to BCR-ABL1-Targeted Therapies. Cancer Cell. 2020 Apr 13;37(4):530-542. doi: 10.1016/j.ccell.2020.03.006.115354Pathway33603017853901Quintas-Cardama A, Kantarjian H, Cortes J: Flying under the radar: the new wave of BCR-ABL inhibitors. Nat Rev Drug Discov. 2007 Oct;6(10):834-48. doi: 10.1038/nrd2324.115354Pathway33603121098337O'Hare T, Deininger MW, Eide CA, Clackson T, Druker BJ: Targeting the BCR-ABL signaling pathway in therapy-resistant Philadelphia chromosome-positive leukemia. Clin Cancer Res. 2011 Jan 15;17(2):212-21. doi: 10.1158/1078-0432.CCR-09-3314. Epub 2010 Nov 22.115354Pathway33603222156549Cilloni D, Saglio G: Molecular pathways: BCR-ABL. Clin Cancer Res. 2012 Feb 15;18(4):930-7. doi: 10.1158/1078-0432.CCR-10-1613. Epub 2011 Dec 8.115354Pathway34674329126136Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.115354Pathway1CellCL:00000004CardiomyocyteCL:00007465HepatocyteCL:00001826MyocyteCL:000018728MacrophageCL:00002351Homo sapiens9606EukaryoteHuman4Arabidopsis thaliana3702EukaryoteThale cress6Caenorhabditis elegans6239EukaryoteRoundworm5CytoplasmGO:00057371CytosolGO:000582919Sarcoplasmic ReticulumGO:001652925Golgi ApparatusGO:000579415NucleusGO:000563410Cell MembraneGO:000588611Extracellular SpaceGO:00056155cardiocyteBTO:00015391LiverBTO:00007597299MuscleBTO:0000887141188Blood VesselBTO:0001102741124BrainBTO:000014289168511PW_BS0000082111PW_BS0000023551914PW_BS000035432511PW_BS000043231511PW_BS0000231644PW_BS00016414101PW_BS000014209106PW_BS000024261115PW_BS0000265291016PW_BS00005227151PW_BS000027711PW_BS000007151141PW_BS000151509516PW_BS0000501171815128PW_BS0005838424111PW_BS00008474082BafetinibHMDB0240206Bafetinib is a tyrosine kinase inhibitor used to treat chronic myelogenous leukemia (CML), a cancer characterized by increased and unregulated growth of white blood cells in the bone marrow and the accumulation of these cells in the blood. Bafetinib is able to bind ABL with greater affinity than Imatinib (25-55 times more potent). It is therefore administered to patients with Imatinib resistance. Notably, Bafetinib is ineffective against the T315I mutation in BCR-ABL, and further research is necessary.859212-16-1113876059562515DB11851CN(C)[C@H]1CCN(CC2=C(C=C(C=C2)C(=O)NC2=CC(NC3=NC=CC(=N3)C3=CN=CN=C3)=C(C)C=C2)C(F)(F)F)C1C30H31F3N8OInChI=1S/C30H31F3N8O/c1-19-4-7-23(13-27(19)39-29-36-10-8-26(38-29)22-14-34-18-35-15-22)37-28(42)20-5-6-21(25(12-20)30(31,32)33)16-41-11-9-24(17-41)40(2)3/h4-8,10,12-15,18,24H,9,11,16-17H2,1-3H3,(H,37,42)(H,36,38,39)/t24-/m0/s1ZGBAJMQHJDFTQJ-DEOSSOPVSA-N576.6153576.257292269INNO 406;NS 187PW_C074082Bafeti438298338RasProteinComplex955ProteinComplexPW_EC000337ChEBIRas800688342AktProteinComplex982ProteinComplexPW_EC000342Akt339RAFProteinComplex1030ProteinComplexPW_EC000339RAF800698340MEKProteinComplex1031ProteinComplexPW_EC000340MEK341MAPKProteinComplex948ProteinComplexPW_EC000341MAPK343FOXOProteinComplex6625ProteinComplexPW_EC000343FOXO13539Bcr-abl1 fusion proteinA8E194Bcr-abl1 fusion protein is a cytoplasm-targeted constitutively active tyrosine kinase that causes uninhibited cell proliferation. This fusion protein is the result of Abelson Murine Leukemia viral oncogene homolog 1 (ABL1) translocating within the Breakpoint Cluster Region (BCR) gene on chromosome 22 and is necessary for Chronic Myeloid Leukemia (CML) pathogenesis.BCR-ABL1143797814629825154Growth factor receptor-bound protein 2P62993Isoform GRB3-3 does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits EGF-induced transactivation of a RAS-responsive element. Isoform GRB3-3 acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active programmed cell deathHMDBP11487GRB217q24-q25AF063614142312655335116548139602435783GRB2-associated-binding protein 2Q9UQC2Adapter protein which acts downstream of several membrane receptors including cytokine, antigen, hormone, cell matrix and growth factor receptors to regulate multiple signaling pathways. Regulates osteoclast differentiation mediating the TNFRSF11A/RANK signaling. In allergic response, it plays a role in mast cells activation and degranulation through PI-3-kinase regulation. Also involved in the regulation of cell proliferation and hematopoiesis.GAB21421624380983798Son of sevenless homolog 1Q07889Promotes the exchange of Ras-bound GDP by GTPHMDBP08580SOS12p21L138571423221165588566Adapter molecule crkP46108
The Crk-I and Crk-II forms differ in their biological activities. Crk-II has less transforming activity than Crk-I. Crk-II mediates attachment-induced MAPK8 activation, membrane ruffling and cell motility in a Rac-dependent manner. Involved in phagocytosis of apoptotic cells and cell motility via its interaction with DOCK1 and DOCK4. May regulate the EFNA5-EPHA3 signaling.
CRK14381088618Crk-like proteinP46109
May mediate the transduction of intracellular signals.
CRKL1438118144865232779E3 ubiquitin-protein ligase CBLP22681Participates in signal transduction in hematopoietic cells. Adapter protein that functions as a negative regulator of many signaling pathways that start from receptors at the cell surface. Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Recognizes activated receptor tyrosine kinases, including PDGFA, EGF and CSF1, and terminates signalingHMDBP07558CBL11q23.3BC13273316.3.2.-92701644381282388Phosphatidylinositol 3-kinase regulatory subunit alphaP27986Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissuesHMDBP03978PIK3R15q13.1AF2793671252814257021166588022320914160826141654529530Signal transducer and activator of transcription 5AP42229
Carries out a dual function: signal transduction and activation of transcription. Mediates cellular responses to the cytokine KITLG/SCF and other growth factors. Mediates cellular responses to ERBB4. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the GAS element and activates PRL-induced transcription. Regulates the expression of milk proteins during lactation.
STAT5A14381388059223889941489156279422971121Tyrosine-protein kinase JAK2O60674Non-receptor tyrosine kinase involved in various processes such as cell cycle progression, apoptosis, mitotic recombination, genetic instability and histone modifications. In the cytoplasm, plays a pivotal role in signal transduction via its association with cytokine receptors, which constitutes an initiating step in signaling for many members of the cytokine receptor superfamily including the receptors for growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), granulocyte-macrophage colony-stimulating factor (CSF2), thrombopoietin (THPO) and multiple interleukins. Following stimulation with erythropoietin (EPO) during erythropoiesis, it is autophosphorylated and activated, leading to its association with erythropoietin receptor (EPOR) and tyrosine phosphorylation of residues in the EPOR cytoplasmic domain. Also involved in promoting the localization of EPOR to the plasma membrane. Also acts downstream of some G-protein coupled receptors. Plays a role in the control of body weight. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatinHMDBP01194JAK29p24AF05892512.7.10.243814888997148506S-phase kinase-associated protein 2Q13309
Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription. Specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. Degradation of CDKN1B/p27kip also requires CKS1. Recognizes target proteins ORC1, CDT1, RBL2, KMT2A/MLL1, CDK9, RAG2, FOXO1, UBP43, and probably MYC, TOB1 and TAL1. Degradation of TAL1 also requires STUB1. Recognizes CDKN1A in association with CCNE1 or CCNE2 and CDK2. Promotes ubiquitination and destruction of CDH1 in a CK1-Dependent Manner, thereby regulating cell migration.
SKP214381589228Cyclin-dependent kinase inhibitor 1BP46527
Important regulator of cell cycle progression. Involved in G1 arrest. Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. Forms a complex with cyclin type D-CDK4 complexes and is involved in the assembly, stability, and modulation of CCND1-CDK4 complex activation. Acts either as an inhibitor or an activator of cyclin type D-CDK4 complexes depending on its phosphorylation state and/or stoichometry.
CDKN1B143816232017Serine/threonine-protein kinase mTORP42345Kinase subunit of both mTORC1 and mTORC2, which regulate cell growth and survival in response to nutrient and hormonal signals. mTORC1 is activated in response to growth factors or amino-acids. Amino-acid-signaling to mTORC1 is mediated by Rag GTPases, which cause amino-acid-induced relocalization of mTOR within the endomembrane system. Growth factor-stimulated mTORC1 activation involves AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-421', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. mTORC2 is also activated by growth factors, but seems to be nutrient- insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'HMDBP02611MTOR1p36.2U8896612.7.11.150442438178135487151141616261416595014387611711325Ribosomal protein S6 kinase beta-1P23443Acts to integrate nutrient and growth factor signals in regulation of protein synthesis, cell proliferation, cell growth, cell cycle progression and cell survival. Downstream effector of the mTOR signaling pathway. Phosphorylates specifically ribosomal protein S6 in response to insulin or several classes of mitogens. During translation initiation, the inactive form associatess with the eIF-3 complex under conditions of nutrient depletion. Mitogenic stimulation leads to phosphorylation and dissociation from the eIF-3 complex and the free activated form can phosphorylate other translational targets including EIF4B. Promotes protein synthesis by phosphorylating PDCD4 at 'Ser-67' and targeting it for degradation. Phosphorylates RICTOR leading to regulation of mammalian target of rapamycin complex 2 (mTORC2) signaling; probably phosphorylates RICTOR at 'Thr-1135'. Phosphorylates IRS1 at multiple serine residues coupled with insulin resistance; probably phosphorylates IRS1 at 'Ser-270'. Required for TNF-alpha induced IRS-1 degradation. Phosphorylates EEF2K in response to IGF1 and inhibits EEF2K activity. Phosphorylates BAD at 'Ser-99' in response to IGF1 leading to BAD inactivation and inhibition of BAD-induced apoptosis. Phosphorylates mitochondrial RMP leading to dissociation of a RMP:PPP1CC complex; probably phosphorylates RMP at 'Ser-99'. The free mitochondrial PPP1CC can dephosphorylate RPS6KB1 at Thr-412 which is proposed to be a negative feed back mechanism for the RPS6KB1 antiapoptotic function. Phosphorylates GSK3B at 'Ser-9' under conditions leading to loss of the TSC1-TSC2 complex. Phosphorylates POLDIP3HMDBP01426RPS6KB117q23.1M6072412.7.11.1504524381885772Bcl2-associated agonist of cell deathQ92934Promotes cell death. Successfully competes for the binding to Bcl-X(L), Bcl-2 and Bcl-W, thereby affecting the level of heterodimerization of these proteins with BAX. Can reverse the death repressor activity of Bcl-X(L), but not that of Bcl-2 (By similarity). Appears to act as a link between growth factor receptor signaling and the apoptotic pathwaysBAD1412624381989121Bcl-2-like protein 1Q07817
Potent inhibitor of cell death. Inhibits activation of caspases. Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.
BCL2L114382081940E3 ubiquitin-protein ligase Mdm2Q00987E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degration by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as an ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of TP53/p53. Promotes proteasome-dependent ubiquitin- independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradationHMDBP02432MDM212q14.3-q15M9242416.3.2.-4382185728Cellular tumor antigen p53P04637TP53AY27015513138261908443822238023888433Myc proto-oncogene proteinP01106
Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. Activates the transcription of growth-related genes.
MYC143823236622BCR-ABL/GRB2/GAB2/SOS1 complex1PW_P00662214353135391435451541435557831435637984379886623BCR-ABL/CRK/CRKL/CBL/PI3K complex1PW_P00662314357135391435885661435986181436027791436123884380083177STAT5A homodimer complex1PW_P0031779103953016629Tyrosine-protein kinase JAK21PW_P0066291436711214380686626S-phase kinase-associated protein 21PW_P0066261436485064380386627cyclin-dependent kinase inhibitor 1B1PW_P0066271436592284380481125Serine/threonine-protein kinase mTOR1PW_P001125128720171112670 kDa ribosomal protein S6 kinase1PW_P001126128813251980Bcl2-associated agonist of cell death1PW_P0009801106577216628Bcl-2-like protein 11PW_P0066281436691214380586621E3 ubiquitin-protein ligase Mdm21PW_P0066211435219404379623762Cellular tumor antigen p531PW_P00076285957286630Myc proto-oncogene protein1PW_P00663014368843343807236631BCR-ABL1PW_P0066311436913539438248213ActivationPW_I0002134256622ProteinComplex1426338ElementCollection1217ActivationPW_I0002174336622ProteinComplex14346623ProteinComplex1218ActivationPW_I0002184356623ProteinComplex1436342ElementCollection1228ActivationPW_I0002284556622ProteinComplex14563177ProteinComplex1229ActivationPW_I0002294576622ProteinComplex14586629ProteinComplex1230ActivationPW_I0002304596629ProteinComplex14603177ProteinComplex1214ActivationPW_I000214427338ElementCollection1428339ElementCollection1215ActivationPW_I000215429339ElementCollection1430340ElementCollection1216ActivationPW_I000216431340ElementCollection1432341ElementCollection1219InhibitionPW_I000219437342ElementCollection1438343ElementCollection1220ActivationPW_I000220439342ElementCollection14406626ProteinComplex1221InhibitionPW_I0002214416626ProteinComplex14426627ProteinComplex1222ActivationPW_I000222443342ElementCollection14441125ProteinComplex1223ActivationPW_I0002234451125ProteinComplex14461126ProteinComplex1224InhibitionPW_I000224447342ElementCollection1448980ProteinComplex1225InhibitionPW_I000225449980ProteinComplex14506628ProteinComplex1226ActivationPW_I000226451342ElementCollection14526621ProteinComplex1227InhibitionPW_I0002274536621ProteinComplex1454762ProteinComplex1231ActivationPW_I0002314616629ProteinComplex14626630ProteinComplex1236InhibitionPW_I00023647174082Compound14726631ProteinComplex13097311740828157false109621510regular200190238643381448false106876512regular15070238653421448false166876012regular15070238663391448false106891512regular15070238673401448false1068106512regular15070238683411448false1068121512regular15070238693431448false1668101512regular1507011953551353982true6084158generegular150701195356515482false9835208generegular150701195357578382false9935758generegular150701195358379882false8735558generegular1507011953591353982true13534058subunitregular150701195360856682false12935609generegular150701195361861882false13885358generegular150701195362277982false12635158generegular150701195363238882false136860010generegular150701195364953082false6739958generegular150701195365112182false8738408generegular150701195366850682false127316158generegular1507011953679228232false127317608generegular150701195368201782false146810158generegular150701195369132582false146812158generegular150701195370577282false186810158generegular150701195371912182false186816158generegular150701195372194082false207310158generegular1507011953735728232false207316158generegular1507011953748433232false86816158generegular150701195375135398116false11165108generegular16080939954662211521781190418119535511904191195356119042011953571190421119535893995566231152178119042211953591190423119536011904241195361119042511953621190426119536393995631771152178119042711953649399576629115217811904281195365939958662611521781190429119536693995966271152172311904301195367939960112511521781190431119536893996111261152178119043211953699399629801152178119043311953709399636628115217811904341195371939964662111521781190435119537293996576211521723119043611953739399666630115217231190437119537493996766311152178119043811953754224425M1143 765 C1096 730 990 652 948 625 149false18trueM 418.94685504416486 13.26155629629604 L 404 12 L 410.38088772118584 25.575134323078345false4224426M948 625 C948 655 1255 673 1255 703 149true184224427M1143 610 C1173 610 1338 635 1368 635 149false18trueM 1415.0096189432334 402.5 L 1428 395 L 1415.0096189432334 387.5false4224428M1773 765 C1743 765 1173 610 1143 610 149true18trueM 348.94685504416486 13.26155629629604 L 334 12 L 340.38088772118584 25.575134323078345false4224429M1743 760 C1671 742 1490 684 1443 670 149false18trueM 576.9468550441649 102.26155629629604 L 562 101 L 568.3808877211858 114.57513432307834false4224430M1443 670 C1443 700 1708 527.5 1708 557.5 149true184224431M948 625 C886 668 804 723 746 764 C746 794 746 944 748 995 149false18trueM 735.5 642.0096189432334 L 743 655 L 750.5 642.0096189432334false4224432M748 995 C748 965 698 754 698 724 149true18trueM 342.94685504416486 39.26155629629604 L 328 38 L 334.38088772118584 51.575134323078345false4224433M948 625 C948 655 948 810 948 840 149false18trueM 970.5 582.0096189432334 L 978 595 L 985.5 582.0096189432334false4224434M948 840 C948 810 1010 786 1010 756 149true18trueM 531.9468550441649 114.26155629629604 L 517 113 L 523.3808877211858 126.57513432307834false4224435M948 910 C876 940 810 970 748 995 149false18trueM 830.9903810567666 682.5 L 818 690 L 830.9903810567666 697.5false4224436M823 1030 C853 1030 788 940 818 940 149true18trueM 572.9468550441649 306.261556296296 L 558 305 L 564.3808877211858 318.5751343230783false4224437M1143 835 C1143 865 1143 885 1143 915 149false18trueM 1215.5 659.5096189432334 L 1223 672.5 L 1230.5 659.5096189432334false4224438M1143 915 C1143 885 1168 952.5 1168 922.5 149true18trueM 765.9468550441649 321.261556296296 L 751 320 L 757.3808877211858 333.5751343230783false4224439M1143 985 C1143 1015 1143 1035 1143 1065 149false18trueM 1215.5 862.0096189432334 L 1223 875 L 1230.5 862.0096189432334false4224440M1143 1065 C1143 1035 1168 1142.5 1168 1112.5 149true18trueM 743.9468550441649 427.261556296296 L 729 426 L 735.3808877211858 439.5751343230783false4224441M1143 1135 C1143 1165 1143 1185 1143 1215 149false18trueM 1215.5 1014.5096189432334 L 1223 1027.5 L 1230.5 1014.5096189432334false4224442M1143 1215 C1143 1185 1168 1307.5 1168 1277.5 149true18trueM 730.9468550441649 505.261556296296 L 716 504 L 722.3808877211858 517.5751343230784false4224443M1743 830 C1743 860 1742 994 1743 1015 148false18falsetrueM 1658 652.5 L 1673 652.5 L 1688 652.54224444M1743 1015 C1743 985 1618 932.5 1618 902.5 148true18falsetrueM 922.565967322979 230.6864219732177 L 914 243 L 905.434032677021 255.31357802678234224445M1743 830 C1679 846 1392 914 1348 928 C1349 947 1348 1595 1348 1615 149false18trueM 1665.5 632.0096189432334 L 1673 645 L 1680.5 632.0096189432334false4224446M1348 1615 C1348 1585 1618 925 1618 895 149true18trueM 1066.9468550441647 343.261556296296 L 1052 342 L 1058.380887721186 355.5751343230783false4224447M1348 1685 C1348 1715 1348 1730 1348 1760 148false18falsetrueM 1663 970 L 1678 970 L 1693 9704224448M1348 1760 C1348 1730 1623 1250 1623 1220 148true18falsetrueM 1021.565967322979 476.6864219732177 L 1013 489 L 1004.434032677021 501.31357802678234224449M1743 830 C1693 857 1585 904 1544 928 C1543 954 1544 984 1543 1015 149false18trueM 2005.5 687.0096189432334 L 2013 700 L 2020.5 687.0096189432334false4224450M1543 1015 C1543 985 1618 925 1618 895 149true18trueM 1137.9468550441647 434.261556296296 L 1123 433 L 1129.380887721186 446.5751343230783false4224451M1543 1085 C1543 1115 1543 1185 1543 1215 149false18trueM 2005.5 832.0096189432334 L 2013 845 L 2020.5 832.0096189432334false4224452M1543 1215 C1543 1185 1958 1125 1958 1095 149true18trueM 1364.9468550441647 412.261556296296 L 1350 411 L 1356.380887721186 424.5751343230783false4224453M1743 830 C1781 848 1910 910 1942 923 C1942 943 1943 994 1943 1015 148false18falsetrueM 2079 733 L 2094 733 L 2109 7334224454M1943 1015 C1943 985 1618 925 1618 895 149true18trueM 1407.9468550441647 411.261556296296 L 1393 410 L 1399.380887721186 423.5751343230783false4224455M1943 1085 C1943 1115 1943 1585 1943 1615 148false18falsetrueM 2093 970 L 2108 970 L 2123 9704224456M1943 1615 C1943 1585 2233 1075 2233 1045 148true18falsetrueM 1653.565967322979 541.6864219732176 L 1645 554 L 1636.434032677021 566.31357802678244224457M1743 830 C1787 837 2114 915 2147 925 C2147 947 2148 989 2148 1015 149false18trueM 2505.5 647.0096189432334 L 2513 660 L 2520.5 647.0096189432334false4224458M2148 1015 C2148 985 1618 925 1618 895 149true18trueM 1561.9468550441647 440.261556296296 L 1547 439 L 1553.380887721186 452.5751343230783false4224459M2148 1085 C2148 1115 2148 1585 2148 1615 148false18falsetrueM 2498 880 L 2513 880 L 2528 8804224460M2148 1615 C2148 1585 2458 1085 2458 1055 148true18falsetrueM 1728.565967322979 328.6864219732177 L 1720 341 L 1711.434032677021 353.31357802678234224461M948 910 C948 940 943 1585 943 1615 149false18trueM 995.5 712.0096189432334 L 1003 725 L 1010.5 712.0096189432334false4224462M943 1615 C943 1585 948 1005 948 975 149true18trueM 547.9468550441649 358.261556296296 L 533 357 L 539.3808877211858 370.5751343230783false4224463M1196 405 C1196 435 1196 480 1196 510 148false18falsetrueM 1331 510 L 1346 510 L 1361 5104224464M1196 510 C1196 480 1196 460 1196 430 148true18falsetrueM 474.565967322979 -0.31357802678230584 L 466 12 L 457.434032677021 24.3135780267823064224465M748 1065 C749 1097 745 1856 746 1879 218false18true793.9428127169396,995.3476589879308 802,1008 808.9286550922654,994.6961006237862false4224466M1143 1285 C1144 1318 1143 1844 1144 1870 218false18true1179.0644009829866,1343.611518094107 1194,1345 1187.7346610946918,1331.371150877582false4224467M943 1685 C976 1720 1049 1817 1096 1870 218false18true1064.0644009829866,1544.611518094107 1079,1546 1072.7346610946918,1532.371150877582false4224468M1943 1685 C1943 1706 1943 1841 1944 1867 218false18true1994.0062802889693,1604.307464982066 2002,1617 2008.995197908439,1603.730968150548false4224469M1743 1085 C1743 1107 1745 1661 1746 1686 C1772 1720 1835 1818 1872 1868 218false19true1825.5,1520.9903810567666 1818,1508 1810.5,1520.9903810567666false4224470M2148 1685 C2133 1705 2043 1833 2017 1864 218false18true2074.601341581382,1599.2272879275004 2072,1614 2086.0942147282685,1608.8664718571474false4224471M1543 1285 C1543 1312 1544 1798 1546 1878 218false18trueM 1670.0644009829866 1197.611518094107 L 1685 1199 L 1678.7346610946918 1185.371150877582false4224472M1348 1830 C1384 1843 1427 1861 1473 1878 218false18true1592.0644009829866,1454.611518094107 1607,1456 1600.7346610946918,1442.371150877582false932521311521782637238644224425Right113729399544224426Left93262171152178113739399544224427Left113749399554224428Right932721811521782638238654224429Right113759399554224430Left93282281152178113769399544224431Left113779399564224432Right93292291152178113789399544224433Left113799399574224434Right93302301152178113809399574224435Left113819399564224436Right933121411521782639238644224437Left2640238664224438Right933221511521782641238664224439Left2642238674224440Right933321611521782643238674224441Left2644238684224442Right933421911521782645238654224443Left2646238694224444Right933522011521782647238654224445Left113829399584224446Right933622111521723113839399584224447Left113849399594224448Right933722211521782648238654224449Left113859399604224450Right93382231152178113869399604224451Left113879399614224452Right933922411521782649238654224453Left113889399624224454Right93402251152178113899399624224455Left113909399634224456Right934122611521782650238654224457Left113919399644224458Right934222711521723113929399644224459Left113939399654224460Right934323111521723113949399574224461Left113959399664224462Right93442361152178248530973114224463Left113969399674224464Right7038442244657038542244667038642244677038742244687038842244697038942244707039042244717039142244724707881658391.01.002904844974707897906481.01.0017471021014707908937161.01.00174710210147079110186611.01.00174710210147079211855741.01.00174710210147079315406641.01.00174710210147079470518511.01.001747102101470795110018511.01.001747102101470796149018561.01.001747102101470797189018511.01.001747102101467061M495 1403 C528 1402 2256 1402 2287 1402 93false61792.01.0467062M495 1505 C515 1505 2250 1502 2286 1502 93false61791.03.0467063M127 229 C127 179 177 129 227 129 C848 129 1655 129 2276 129 C2326 129 2376 179 2376 229 C2376 804 2376 1551 2376 2126 C2376 2176 2326 2226 2276 2226 C1655 2226 848 2226 227 2226 C177 2226 127 2176 127 2126 C127 1551 127 804 127 229 1true62249.02097.087195515Nucleus Outer Membrane5381365201.01.01601587195615Nucleus Inner Membrane5331470201.01.016015871957235Transcription10401861191.01.020015871958235Proliferation and Survival6401866191.01.020015871959235Survival18381861191.01.020015871960235Protein Synthesis14381294201.01.02001587196115PI3K/Akt Pathway1633642201.61.61601587196215MAPK/ERK Pathway1112652201.61.616015871963235Proliferation14341866191.01.020015871964235Cytosol209162202.22.22001587196515JAK-STAT Pathway534638201.61.61601587196615Decreased signalling of the JAK-STAT pathway decreases the cell's likelihood for proliferation and survival. 5601968202.22.21601587196715Both the JAK-STAT pathway and the MAPK/ERK pathway influence the cell's transcription. Inhibiting these pathways decreases transcription so the cell will eventually die. 9751963201.91.91601587196815The PI3K/AKT pathway is responsible for many regulatory functions of the cell and it's inhibition would affect downstream processes of protein synthesis and cellular proliferation. 13621953201.91.91601587196915With decreased protein synthesis, less cellular functions will be able to proceed eventually killing the cell.16941985201.91.91601587197115Dasatinib specifically binds and inhibits the BCR/ABL1 fusion protein tyrosine kinase. The BCR-ABL1 is an abnormal enzyme created by the Philadelphia chromosomal translocation. This chromosomal translocation is associated with chronic myeloid leukemia .742230201.91.91601587197215Inhibition of BCR/ABL1 inhibits the JAK-STAT, MAPK/ERK, and PI3K/Akt pathways cascade effects.1562475201.91.916015279520368112449413752288198539#FFF9C941794610