Details of the Drug Combination

General Information of Drug Combination (ID: DCKYH61)

Drug Combination Name
Isoproterenol Imatinib
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Isoproterenol   DMK7MEY Imatinib   DM7RJXL
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 6.47
Bliss Independence Score: 6.47
Loewe Additivity Score: 9.27
LHighest Single Agent (HSA) Score: 9.35

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Isoproterenol
Disease Entry ICD 11 Status REF
Atrioventricular block N.A. Approved [2]
Cardiac arrest MC82 Approved [2]
Common cold CA00 Approved [2]
Heart block BC63 Approved [3]
Melanoma 2C30 Phase 1 [4]
Isoproterenol Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Adrenergic receptor beta-1 (ADRB1) TTR6W5O ADRB1_HUMAN Agonist [13]
Adrenergic receptor beta-2 (ADRB2) TT2CJVK ADRB2_HUMAN Modulator [13]
Interleukin-12 beta (IL12B) TTGW72V IL12B_HUMAN Modulator [14]
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Isoproterenol Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Thiopurine methyltransferase (TPMT) DEFQ8VO TPMT_HUMAN Metabolism [15]
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Isoproterenol Interacts with 74 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Expression [16]
Apoptotic protease-activating factor 1 (APAF1) OTJWIVY0 APAF_HUMAN Increases Expression [12]
ATP-binding cassette sub-family C member 3 (ABCC3) OTC3IJV4 MRP3_HUMAN Decreases Expression [12]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Increases Expression [12]
Complement C3 (C3) OTCH5GS0 CO3_HUMAN Decreases Expression [12]
Metalloproteinase inhibitor 1 (TIMP1) OTOXC51H TIMP1_HUMAN Decreases Expression [12]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Decreases Expression [12]
Interleukin-1 alpha (IL1A) OTPSGILV IL1A_HUMAN Decreases Expression [12]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Decreases Expression [12]
Interleukin-4 (IL4) OTOXBWAU IL4_HUMAN Decreases Expression [12]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Expression [12]
C-C motif chemokine 3 (CCL3) OTW2H3ND CCL3_HUMAN Increases Expression [12]
Endoplasmic reticulum chaperone BiP (HSPA5) OTFUIRAO BIP_HUMAN Decreases Expression [12]
Heat shock cognate 71 kDa protein (HSPA8) OTJI2RCI HSP7C_HUMAN Decreases Expression [12]
Interleukin-7 (IL7) OTT6YSKM IL7_HUMAN Increases Expression [12]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) OT2D9DOV TNR1A_HUMAN Decreases Expression [12]
Phosphatidylcholine translocator ABCB4 (ABCB4) OTE6PY83 MDR3_HUMAN Decreases Expression [12]
Caspase-1 (CASP1) OTZ3YQFU CASP1_HUMAN Decreases Expression [12]
14-3-3 protein sigma (SFN) OTLJCZ1U 1433S_HUMAN Decreases Expression [12]
Heat shock 70 kDa protein 1-like (HSPA1L) OTC2V1K6 HS71L_HUMAN Decreases Expression [12]
Nitric oxide synthase, inducible (NOS2) OTKKIOJ1 NOS2_HUMAN Decreases Expression [12]
Metalloproteinase inhibitor 3 (TIMP3) OTDGQAD1 TIMP3_HUMAN Increases Expression [12]
Aryl hydrocarbon receptor (AHR) OTFE4EYE AHR_HUMAN Increases Expression [12]
Heat shock-related 70 kDa protein 2 (HSPA2) OTSDET7B HSP72_HUMAN Increases Expression [12]
C-C motif chemokine 7 (CCL7) OTDIS99H CCL7_HUMAN Decreases Expression [12]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Decreases Expression [12]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [12]
Four and a half LIM domains protein 1 (FHL1) OTN535SU FHL1_HUMAN Decreases Expression [12]
Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) OTXEE550 APR_HUMAN Increases Expression [12]
Bcl-2 homologous antagonist/killer (BAK1) OTDP6ILW BAK_HUMAN Decreases Expression [12]
Regenerating islet-derived protein 3-gamma (REG3G) OTLIUY8Z REG3G_HUMAN Decreases Expression [12]
Metalloproteinase inhibitor 4 (TIMP4) OT8A68SW TIMP4_HUMAN Decreases Expression [12]
Aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) OTAQD3YV ARNT2_HUMAN Decreases Expression [12]
Hypoxia-inducible factor 1-alpha inhibitor (HIF1AN) OT5LIL3W HIF1N_HUMAN Decreases Expression [12]
Hypoxia-inducible factor 3-alpha (HIF3A) OTPWAAMC HIF3A_HUMAN Increases Expression [12]
Proepiregulin (EREG) OTRM4NQY EREG_HUMAN Increases Expression [17]
Superoxide dismutase (SOD1) OT39TA1L SODC_HUMAN Affects Binding [18]
Renin (REN) OT52GZR2 RENI_HUMAN Increases Activity [19]
Angiotensinogen (AGT) OTBZLYR3 ANGT_HUMAN Increases Expression [20]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Decreases Expression [21]
Natriuretic peptides A (NPPA) OTMQNTNX ANF_HUMAN Increases Expression [22]
Interferon gamma (IFNG) OTXG9JM7 IFNG_HUMAN Decreases Secretion [23]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Decreases Expression [17]
Fibronectin (FN1) OTB5ZN4Q FINC_HUMAN Decreases Expression [21]
Transferrin receptor protein 1 (TFRC) OT8ZPBDL TFR1_HUMAN Decreases Expression [24]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Increases Expression [17]
Alkaline phosphatase, placental type (ALPP) OTZU4G9W PPB1_HUMAN Increases Expression [25]
Beta-2 adrenergic receptor (ADRB2) OTSDOX4Q ADRB2_HUMAN Increases Expression [26]
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Increases Expression [27]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [27]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Decreases Expression [28]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [17]
Cystic fibrosis transmembrane conductance regulator (CFTR) OT6B22QH CFTR_HUMAN Increases Activity [29]
Beta-3 adrenergic receptor (ADRB3) OTPMG4V7 ADRB3_HUMAN Increases Activity [30]
Matrix metalloproteinase-9 (MMP9) OTB2QDAV MMP9_HUMAN Increases Expression [31]
Natriuretic peptides B (NPPB) OTSN2IPY ANFB_HUMAN Increases Expression [22]
Beta-adrenergic receptor kinase 1 (GRK2) OT34KKWK ARBK1_HUMAN Increases Expression [32]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [33]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [33]
Beta-arrestin-2 (ARRB2) OTAEJZCI ARRB2_HUMAN Affects Localization [34]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Decreases Expression [17]
Leptin (LEP) OT5Q7ODW LEP_HUMAN Decreases Secretion [35]
Tumor necrosis factor-inducible gene 6 protein (TNFAIP6) OT1SLUZH TSG6_HUMAN Decreases Expression [17]
Interleukin-24 (IL24) OT4VUWH1 IL24_HUMAN Increases Expression [17]
C-C motif chemokine 17 (CCL17) OTIKW21L CCL17_HUMAN Decreases Secretion [36]
Ryanodine receptor 2 (RYR2) OT0PF19E RYR2_HUMAN Increases Phosphorylation [37]
Cystine/glutamate transporter (SLC7A11) OTKJ6PXW XCT_HUMAN Increases Expression [17]
Interleukin-1 receptor antagonist protein (IL1RN) OT308CBE IL1RA_HUMAN Affects Response To Substance [38]
Dystroglycan 1 (DAG1) OT6QBA05 DAG1_HUMAN Increases ADR [39]
Bone morphogenetic protein 10 (BMP10) OTA3QKKG BMP10_HUMAN Decreases Response To Substance [40]
Guanine nucleotide-binding protein G(olf) subunit alpha (GNAL) OTESDTEU GNAL_HUMAN Increases Response To Substance [41]
Neuroendocrine secretory protein 55 (GNAS) OTMH8BKJ GNAS3_HUMAN Increases Response To Substance [41]
Interleukin-5 receptor subunit alpha (IL5RA) OTMSLUG9 IL5RA_HUMAN Affects Response To Substance [38]
Catechol O-methyltransferase (COMT) OTPWKTQG COMT_HUMAN Increases Methylation [42]
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⏷ Show the Full List of 74 DOT(s)
Indication(s) of Imatinib
Disease Entry ICD 11 Status REF
Acute lymphoblastic leukaemia 2A85 Approved [5]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive N.A. Approved [6]
Choroidal neovascularization 9B76 Approved [6]
Chronic eosinophilic leukemia N.A. Approved [6]
Chronic myelogenous leukaemia 2A20.0 Approved [7]
Chronic myeloid leukaemia 2A20 Approved [8]
Dermatofibrosarcoma protuberans N.A. Approved [6]
Gastrointestinal stromal tumour 2B5B Approved [6]
Leukemia N.A. Approved [6]
Malignant peripheral nerve sheath tumor N.A. Approved [6]
Myeloproliferative neoplasm 2A20 Approved [6]
Pulmonary hypertension BB01 Approved [6]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [9]
Intestinal cancer 2C0Z Phase 3 [7]
Lung cancer 2C25.0 Phase 2 [7]
Idiopathic hypereosinophilic syndrome N.A. Investigative [6]
Middle East Respiratory Syndrome (MERS) 1D64 Investigative [10]
Scleroderma 4A42 Investigative [6]
Severe acute respiratory syndrome (SARS) 1D65 Investigative [10]
Systemic mastocytosis 2A21.0 Investigative [11]
Imatinib Interacts with 5 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Mcl-1 messenger RNA (MCL-1 mRNA) TTN6ORK MCL1_HUMAN . [11]
Fusion protein Bcr-Abl (Bcr-Abl) TTS7G69 BCR_HUMAN-ABL1_HUMAN Inhibitor [46]
Platelet-derived growth factor receptor (PDGFR) TTI2WET NOUNIPROTAC Inhibitor [46]
Tyrosine-protein kinase Kit (KIT) TTX41N9 KIT_HUMAN Inhibitor [46]
HUMAN fusion protein Bcr-Abl (Bcr-Abl) TTE63HY BCR_HUMAN/ABL1_HUMAN Inhibitor [10]
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Imatinib Interacts with 6 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [47]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [48]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [49]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [50]
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTE2B1D SO1A2_HUMAN Substrate [51]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [49]
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⏷ Show the Full List of 6 DTP(s)
Imatinib Interacts with 8 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [52]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [53]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [54]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [55]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [56]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [57]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [58]
Prostaglandin G/H synthase 1 (COX-1) DE073H6 PGH1_HUMAN Metabolism [54]
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⏷ Show the Full List of 8 DME(s)
Imatinib Interacts with 95 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Decreases Methylation [59]
Cytochrome P450 3A5 (CYP3A5) OTSXFBXB CP3A5_HUMAN Decreases Methylation [59]
Cytochrome P450 3A7 (CYP3A7) OTTCDHHM CP3A7_HUMAN Decreases Methylation [59]
Cytochrome P450 2C8 (CYP2C8) OTHCWT42 CP2C8_HUMAN Decreases Methylation [59]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Increases Expression [60]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [60]
Aldehyde dehydrogenase, mitochondrial (ALDH2) OTKJ9I3N ALDH2_HUMAN Decreases Expression [61]
Eukaryotic translation initiation factor 4E (EIF4E) OTDAWNLA IF4E_HUMAN Decreases Expression [61]
Fructose-bisphosphate aldolase C (ALDOC) OTEC13I5 ALDOC_HUMAN Decreases Expression [61]
Pyruvate dehydrogenase E1 component subunit beta, mitochondrial (PDHB) OT2NHE5E ODPB_HUMAN Decreases Expression [61]
Cyclin-dependent kinase 4 (CDK4) OT7EP05T CDK4_HUMAN Decreases Expression [61]
Cyclin-A2 (CCNA2) OTPHHYZJ CCNA2_HUMAN Decreases Expression [61]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Decreases Expression [61]
Eukaryotic translation initiation factor 4B (EIF4B) OTE8TXA8 IF4B_HUMAN Decreases Expression [61]
Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1) OT5BZ1J9 P85A_HUMAN Decreases Expression [61]
G1/S-specific cyclin-D3 (CCND3) OTNKPQ22 CCND3_HUMAN Decreases Expression [61]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Expression [61]
Hexokinase-4 (GCK) OTR3Q0NN HXK4_HUMAN Decreases Expression [61]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Decreases Expression [61]
Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform (PPP2CA) OT83PT85 PP2AA_HUMAN Increases Expression [61]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Decreases Expression [61]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [62]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Decreases Expression [63]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Increases Expression [64]
Autophagy-related protein 13 (ATG13) OTYMHNEJ ATG13_HUMAN Increases Phosphorylation [43]
Platelet-derived growth factor subunit B (PDGFB) OTMFMFC3 PDGFB_HUMAN Decreases Expression [65]
Interferon gamma (IFNG) OTXG9JM7 IFNG_HUMAN Increases Expression [66]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Secretion [67]
Keratin, type I cytoskeletal 14 (KRT14) OTUVZ1DW K1C14_HUMAN Increases Expression [68]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [69]
Heat shock protein beta-1 (HSPB1) OTHFZ8ED HSPB1_HUMAN Increases Expression [64]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Activity [70]
Intercellular adhesion molecule 1 (ICAM1) OTTOIX77 ICAM1_HUMAN Increases Expression [64]
Tyrosine-protein kinase Lck (LCK) OT883FG9 LCK_HUMAN Decreases Phosphorylation [71]
Cyclin-dependent kinase 1 (CDK1) OTW1SC2N CDK1_HUMAN Decreases Expression [66]
Cathepsin B (CTSB) OTP9G5QB CATB_HUMAN Increases Expression [43]
Proto-oncogene tyrosine-protein kinase receptor Ret (RET) OTLU040A RET_HUMAN Decreases Phosphorylation [72]
ATP-dependent 6-phosphofructokinase, muscle type (PFKM) OT1QY9JM PFKAM_HUMAN Decreases Expression [73]
Platelet-derived growth factor receptor beta (PDGFRB) OTYSNK9Q PGFRB_HUMAN Decreases Expression [65]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [74]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [64]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [75]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1) OTA675TJ GTR1_HUMAN Decreases Expression [69]
Breakpoint cluster region protein (BCR) OTCN76C1 BCR_HUMAN Decreases Activity [45]
Lysosome-associated membrane glycoprotein 1 (LAMP1) OTYE92QY LAMP1_HUMAN Increases Expression [43]
Ornithine decarboxylase (ODC1) OTNDAGRR DCOR_HUMAN Increases Expression [64]
Keratin, type II cytoskeletal 5 (KRT5) OTVGI9HT K2C5_HUMAN Increases Expression [68]
Tissue factor (F3) OT3MSU3B TF_HUMAN Increases Expression [76]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [77]
Platelet-derived growth factor receptor alpha (PDGFRA) OTDJXUCN PGFRA_HUMAN Decreases Expression [65]
CCAAT/enhancer-binding protein beta (CEBPB) OTM9MQIA CEBPB_HUMAN Increases Expression [64]
Histidine decarboxylase (HDC) OT4WA5YQ DCHS_HUMAN Decreases Expression [78]
Transcription factor EB (TFEB) OTJUJJQY TFEB_HUMAN Affects Localization [43]
Fibroblast growth factor receptor 3 (FGFR3) OTSAXDIL FGFR3_HUMAN Decreases Expression [79]
Insulin-like growth factor-binding protein 4 (IGFBP4) OT2HZRBD IBP4_HUMAN Increases Expression [64]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [80]
Interleukin-4 receptor subunit alpha (IL4R) OTTXOTCW IL4RA_HUMAN Increases Expression [64]
Cyclin-dependent kinase 2 (CDK2) OTB5DYYZ CDK2_HUMAN Decreases Expression [66]
NF-kappa-B inhibitor alpha (NFKBIA) OTFT924M IKBA_HUMAN Increases Phosphorylation [64]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [71]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [71]
Caspase-1 (CASP1) OTZ3YQFU CASP1_HUMAN Increases Cleavage [67]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Decreases Expression [81]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [82]
Crk-like protein (CRKL) OTOYSD1R CRKL_HUMAN Decreases Phosphorylation [83]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Increases Phosphorylation [43]
Hexokinase-2 (HK2) OTC0GCQO HXK2_HUMAN Decreases Expression [73]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [43]
Heat shock factor protein 1 (HSF1) OTYNJ4KP HSF1_HUMAN Increases Expression [64]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Decreases Expression [81]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [75]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [84]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [74]
Forkhead box protein M1 (FOXM1) OT5887KR FOXM1_HUMAN Decreases Expression [81]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [85]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Increases Expression [43]
Beclin-1 (BECN1) OT4X293M BECN1_HUMAN Increases Expression [43]
Nuclear receptor subfamily 0 group B member 2 (NR0B2) OT7UVICX NR0B2_HUMAN Increases Expression [86]
NGFI-A-binding protein 2 (NAB2) OTG4BDF3 NAB2_HUMAN Increases Expression [64]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Decreases Expression [87]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [70]
TRAF family member-associated NF-kappa-B activator (TANK) OTZSGFIK TANK_HUMAN Increases Expression [64]
NACHT, LRR and PYD domains-containing protein 3 (NLRP3) OTZM6MHU NLRP3_HUMAN Increases Expression [67]
Bile acid receptor (NR1H4) OTWZLPTB NR1H4_HUMAN Increases Activity [86]
Docking protein 1 (DOK1) OTGVRLW6 DOK1_HUMAN Decreases Phosphorylation [88]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) OTUYHB84 MLP3B_HUMAN Increases Expression [43]
Transcription factor SOX-17 (SOX17) OT9H4WWE SOX17_HUMAN Decreases Localization [89]
V-type proton ATPase subunit H (ATP6V1H) OTX17GQ9 VATH_HUMAN Increases Expression [43]
Tyrosine-protein kinase ABL1 (ABL1) OT09YVXH ABL1_HUMAN Increases Response To Substance [90]
LYR motif-containing protein 9 (LYRM9) OT1MILTK LYRM9_HUMAN Affects Response To Substance [91]
Leptin (LEP) OT5Q7ODW LEP_HUMAN Increases ADR [39]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Response To Substance [92]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Increases Response To Substance [93]
Tyrosine-protein kinase Lyn (LYN) OTP686K2 LYN_HUMAN Decreases Response To Substance [83]
Serine/threonine-protein kinase PLK1 (PLK1) OTRZX45T PLK1_HUMAN Increases Response To Substance [74]
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⏷ Show the Full List of 95 DOT(s)

References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 Isoproterenol FDA Label
3 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 083346.
4 A phase 1 study of AS1409, a novel antibody-cytokine fusion protein, in patients with malignant melanoma or renal cell carcinoma. Clin Cancer Res. 2011 Apr 1;17(7):1998-2005.
5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
6 Imatinib FDA Label
7 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5687).
8 FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 078340.
9 ClinicalTrials.gov (NCT04356495) Treatments to Decrease the Risk of Hospitalization or Death in Elderly Outpatients With Symptomatic SARS-CoV-2 Infection (COVID-19). U.S. National Institutes of Health.
10 Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
11 Design and development of antisense drugs. Expert Opin. Drug Discov. 2008 3(10):1189-1207.
12 Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo. Toxicol Appl Pharmacol. 2014 Jan 15;274(2):302-12.
13 Current therapeutic uses and potential of beta-adrenoceptor agonists and antagonists. Eur J Clin Pharmacol. 1998 Feb;53(6):389-404.
14 A phase 1 study of AS1409, a novel antibody-cytokine fusion protein, in patients with malignant melanoma or renal cell carcinoma. Clin Cancer Res. 2011 Apr 1;17(7):1998-2005.
15 Identification, characterization, and ontogenic study of a catechol O-methyltransferase from zebrafish. Aquat Toxicol. 2011 Mar;102(1-2):18-23.
16 Role of adrenoceptor-linked signaling pathways in the regulation of CYP1A1 gene expression. Biochem Pharmacol. 2005 Jan 15;69(2):277-87.
17 An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
18 Ligand binding and aggregation of pathogenic SOD1. Nat Commun. 2013;4:1758. doi: 10.1038/ncomms2750.
19 Hypokalemia from beta2-receptor stimulation by circulating epinephrine. N Engl J Med. 1983 Dec 8;309(23):1414-9. doi: 10.1056/NEJM198312083092303.
20 Vascular renin-angiotensin system and neurotransmission in hypertensive persons. Hypertension. 1991 Sep;18(3):266-77. doi: 10.1161/01.hyp.18.3.266.
21 The regulation of human vascular smooth muscle extracellular matrix protein production by alpha- and beta-adrenoceptor stimulation. J Hypertens. 2002 Feb;20(2):287-94. doi: 10.1097/00004872-200202000-00019.
22 Low doses of BPF-induced hypertrophy in cardiomyocytes derived from human embryonic stem cells via disrupting the mitochondrial fission upon the interaction between ER and calcineurin A-DRP1 signaling pathway. Cell Biol Toxicol. 2022 Jun;38(3):409-426. doi: 10.1007/s10565-021-09615-y. Epub 2021 May 22.
23 Post-receptorial mechanisms underlie functional disregulation of beta2-adrenergic receptors in lymphocytes from Multiple Sclerosis patients. J Neuroimmunol. 2004 Oct;155(1-2):143-9. doi: 10.1016/j.jneuroim.2004.05.013.
24 Prostaglandin E2 acts at two distinct pathways of T lymphocyte activation: inhibition of interleukin 2 production and down-regulation of transferrin receptor expression. J Immunol. 1985 Aug;135(2):1172-9.
25 The effects of desmethylimipramine on cyclic AMP-stimulated gene transcription in a model cell system. Biochem Pharmacol. 2005 Sep 1;70(5):762-9. doi: 10.1016/j.bcp.2005.06.012.
26 Isoproterenol inhibits angiotensin II-stimulated proliferation and reactive oxygen species production in vascular smooth muscle cells through heme oxygenase-1. Biol Pharm Bull. 2009 Jun;32(6):1047-52. doi: 10.1248/bpb.32.1047.
27 Quercetin-3-O-glucuronide inhibits noradrenaline-promoted invasion of MDA-MB-231 human breast cancer cells by blocking ?-adrenergic signaling. Arch Biochem Biophys. 2014 Sep 1;557:18-27. doi: 10.1016/j.abb.2014.05.030. Epub 2014 Jun 11.
28 Impaired PARP activity in response to the -adrenergic receptor agonist isoproterenol. Toxicol In Vitro. 2018 Aug;50:29-39. doi: 10.1016/j.tiv.2018.02.001. Epub 2018 Feb 10.
29 Activation of airway cl- secretion in human subjects by adenosine. Am J Respir Cell Mol Biol. 2004 Aug;31(2):140-6. doi: 10.1165/rcmb.2004-0012OC. Epub 2004 Mar 23.
30 Discovery of a novel series of biphenyl benzoic acid derivatives as highly potent and selective human beta3 adrenergic receptor agonists with good oral bioavailability. Part II. J Med Chem. 2008 Jul 10;51(13):4002-20. doi: 10.1021/jm8000345. Epub 2008 Jun 14.
31 Adrenoceptor blockade alters plasma gelatinase activity in patients with heart failure and MMP-9 promoter activity in a human cell line (ECV304). Pharmacol Res. 2006 Jul;54(1):57-64. doi: 10.1016/j.phrs.2006.02.006. Epub 2006 Feb 28.
32 Reciprocal in vivo regulation of myocardial G protein-coupled receptor kinase expression by beta-adrenergic receptor stimulation and blockade. Circulation. 1998 Oct 27;98(17):1783-9. doi: 10.1161/01.cir.98.17.1783.
33 A unique mechanism of beta-blocker action: carvedilol stimulates beta-arrestin signaling. Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16657-62. doi: 10.1073/pnas.0707936104. Epub 2007 Oct 9.
34 Regulation of beta-adrenergic receptor signaling by S-nitrosylation of G-protein-coupled receptor kinase 2. Cell. 2007 May 4;129(3):511-22. doi: 10.1016/j.cell.2007.02.046.
35 Catecholamines suppress leptin release from in vitro differentiated subcutaneous human adipocytes in primary culture via beta1- and beta2-adrenergic receptors. Eur J Endocrinol. 2000 Sep;143(3):439-45. doi: 10.1530/eje.0.1430439.
36 IL-13 and IL-4 promote TARC release in human airway smooth muscle cells: role of IL-4 receptor genotype. Am J Physiol Lung Cell Mol Physiol. 2003 Oct;285(4):L907-14. doi: 10.1152/ajplung.00120.2003. Epub 2003 Jul 18.
37 Carvedilol and its new analogs suppress arrhythmogenic store overload-induced Ca2+ release. Nat Med. 2011 Jul 10;17(8):1003-9. doi: 10.1038/nm.2406.
38 Autocrine interaction between IL-5 and IL-1beta mediates altered responsiveness of atopic asthmatic sensitized airway smooth muscle. J Clin Invest. 1999 Sep;104(5):657-67. doi: 10.1172/JCI7137.
39 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
40 BMP10 preserves cardiac function through its dual activation of SMAD-mediated and STAT3-mediated pathways. J Biol Chem. 2019 Dec 27;294(52):19877-19888. doi: 10.1074/jbc.RA119.010943. Epub 2019 Nov 11.
41 Identification of specific ligands for orphan olfactory receptors. G protein-dependent agonism and antagonism of odorants. J Biol Chem. 2005 Mar 25;280(12):11807-15. doi: 10.1074/jbc.M411508200. Epub 2004 Dec 14.
42 Molecular mechanisms controlling the rate and specificity of catechol O-methylation by human soluble catechol O-methyltransferase. Mol Pharmacol. 2001 Feb;59(2):393-402. doi: 10.1124/mol.59.2.393.
43 Imatinib disturbs lysosomal function and morphology and impairs the activity of mTORC1 in human hepatocyte cell lines. Food Chem Toxicol. 2022 Apr;162:112869. doi: 10.1016/j.fct.2022.112869. Epub 2022 Feb 16.
44 Insulin-like growth factor I receptor pathway inhibition by ADW742, alone or in combination with imatinib, doxorubicin, or vincristine, is a novel therapeutic approach in Ewing tumor. Clin Cancer Res. 2006 Jun 1;12(11 Pt 1):3532-40. doi: 10.1158/1078-0432.CCR-05-1778.
45 Sensitivity to imatinib therapy may be predicted by testing Wilms tumor gene expression and colony growth after a short in vitro incubation. Cancer. 2004 Sep 1;101(5):979-88. doi: 10.1002/cncr.20457.
46 A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
47 Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
48 Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.
49 Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
50 Pharmacologic markers and predictors of responses to imatinib therapy in patients with chronic myeloid leukemia. Leuk Lymphoma. 2008 Apr;49(4):639-42.
51 Environmental and genetic factors affecting transport of imatinib by OATP1A2. Clin Pharmacol Ther. 2011 Jun;89(6):816-20.
52 Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
53 The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats. Biomed Res Int. 2013;2013:789184.
54 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
55 Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94.
56 Drug Interactions Flockhart Table
57 Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
58 Drug-drug interactions with imatinib: an observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076.
59 Participation of CYP2C8 and CYP3A4 in the N-demethylation of imatinib in human hepatic microsomes. Br J Pharmacol. 2010 Nov;161(5):1059-69. doi: 10.1111/j.1476-5381.2010.00946.x.
60 Chronic imatinib mesylate exposure leads to reduced intracellular drug accumulation by induction of the ABCG2 (BCRP) and ABCB1 (MDR1) drug transport pumps. Cancer Biol Ther. 2005 Jul;4(7):747-52.
61 A systems biology understanding of the synergistic effects of arsenic sulfide and Imatinib in BCR/ABL-associated leukemia. Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3378-83.
62 Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.
63 Anti-leukemic effects of gallic acid on human leukemia K562 cells: downregulation of COX-2, inhibition of BCR/ABL kinase and NF-B inactivation. Toxicol In Vitro. 2012 Apr;26(3):396-405.
64 Effects of Imatinib Mesylate (Gleevec) on human islet NF-kappaB activation and chemokine production in vitro. PLoS One. 2011;6(9):e24831. doi: 10.1371/journal.pone.0024831. Epub 2011 Sep 14.
65 Chemosensitization by STI571 targeting the platelet-derived growth factor/platelet-derived growth factor receptor-signaling pathway in the tumor progression and angiogenesis of gastric carcinoma. Cancer. 2005 May 1;103(9):1800-9. doi: 10.1002/cncr.20973.
66 Imatinib mesylate, a new kid on the block for the treatment of anti-neutrophil cytoplasmic autoantibodies-associated vasculitis?. Clin Exp Immunol. 2008 Mar;151(3):391-8. doi: 10.1111/j.1365-2249.2007.03572.x. Epub 2008 Jan 10.
67 Imatinib-induced hepatotoxicity via oxidative stress and activation of NLRP3 inflammasome: an in vitro and in vivo study. Arch Toxicol. 2022 Apr;96(4):1075-1087. doi: 10.1007/s00204-022-03245-x. Epub 2022 Feb 22.
68 Oral lichenoid eruption secondary to imatinib (Glivec). J Dermatolog Treat. 2004 Jul;15(4):253-5. doi: 10.1080/09546630410015556.
69 AMP-activated protein kinase activation primes cytoplasmic translocation and autophagic degradation of the BCR-ABL protein in CML cells. Cancer Sci. 2021 Jan;112(1):194-204. doi: 10.1111/cas.14698. Epub 2020 Nov 16.
70 Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
71 Imatinib mesylate inhibits T-cell proliferation in vitro and delayed-type hypersensitivity in vivo. Blood. 2004 Aug 15;104(4):1094-9. doi: 10.1182/blood-2003-12-4266. Epub 2004 Apr 20.
72 Dual inhibition of RET and FGFR4 restrains medullary thyroid cancer cell growth. Clin Cancer Res. 2005 Feb 1;11(3):1336-41.
73 Combination of imatinib and clotrimazole enhances cell growth inhibition in T47D breast cancer cells. Chem Biol Interact. 2015 May 25;233:147-56. doi: 10.1016/j.cbi.2015.03.028. Epub 2015 Apr 8.
74 Efficacy of the polo-like kinase inhibitor rigosertib, alone or in combination with Abelson tyrosine kinase inhibitors, against break point cluster region-c-Abelson-positive leukemia cells. Oncotarget. 2015 Aug 21;6(24):20231-40. doi: 10.18632/oncotarget.4047.
75 Saikosaponin D disrupts platelet-derived growth factor- receptor/p38 pathway leading to mitochondrial apoptosis in human LO2 hepatocyte cells: a potential mechanism of hepatotoxicity. Chem Biol Interact. 2013 Oct 25;206(1):76-82. doi: 10.1016/j.cbi.2013.08.006. Epub 2013 Aug 28.
76 Elucidating mechanisms of toxicity using phenotypic data from primary human cell systems--a chemical biology approach for thrombosis-related side effects. Int J Mol Sci. 2015 Jan 5;16(1):1008-29. doi: 10.3390/ijms16011008.
77 Proapoptotic activity of bortezomib in gastrointestinal stromal tumor cells. Cancer Res. 2010 Jan 1;70(1):150-9. doi: 10.1158/0008-5472.CAN-09-1449. Epub 2009 Dec 22.
78 The CML-related oncoprotein BCR/ABL induces expression of histidine decarboxylase (HDC) and the synthesis of histamine in leukemic cells. Blood. 2006 Nov 15;108(10):3538-47. doi: 10.1182/blood-2005-12-028456. Epub 2006 Jul 18.
79 Increased expression of fibroblast growth factor receptor 3 in CD34+ BCR-ABL+ cells from patients with chronic myeloid leukemia. Leukemia. 2003 Dec;17(12):2418-25. doi: 10.1038/sj.leu.2403152.
80 Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes. Toxicol Lett. 2018 Jul;291:138-148. doi: 10.1016/j.toxlet.2018.04.010. Epub 2018 Apr 12.
81 Anthelmintic Niclosamide Disrupts the Interplay of p65 and FOXM1/-catenin and Eradicates Leukemia Stem Cells in Chronic Myelogenous Leukemia. Clin Cancer Res. 2017 Feb 1;23(3):789-803. doi: 10.1158/1078-0432.CCR-16-0226. Epub 2016 Aug 4.
82 In vitro studies of the combination of imatinib mesylate (Gleevec) and arsenic trioxide (Trisenox) in chronic myelogenous leukemia. Exp Hematol. 2002 Jul;30(7):729-37. doi: 10.1016/s0301-472x(02)00836-6.
83 Establishment and characterization of a novel imatinib-sensitive chronic myeloid leukemia cell line MYL, and an imatinib-resistant subline MYL-R showing overexpression of Lyn. Eur J Haematol. 2007 May;78(5):417-31. doi: 10.1111/j.1600-0609.2007.00835.x.
84 The catalytic DNA topoisomerase II inhibitor dexrazoxane (ICRF-187) induces differentiation and apoptosis in human leukemia K562 cells. Mol Pharmacol. 2001 Mar;59(3):453-61. doi: 10.1124/mol.59.3.453.
85 Downregulation of hERG channel expression by tyrosine kinase inhibitors nilotinib and vandetanib predominantly contributes to arrhythmogenesis. Toxicol Lett. 2022 Jul 15;365:11-23. doi: 10.1016/j.toxlet.2022.06.001. Epub 2022 Jun 6.
86 Investigation of imatinib and other approved drugs as starting points for antidiabetic drug discovery with FXR modulating activity. Biochem Pharmacol. 2012 Jun 15;83(12):1674-81. doi: 10.1016/j.bcp.2012.02.027. Epub 2012 Mar 7.
87 A new strategy for the rapid identification and validation of direct toxicity targets of psoralen-induced hepatotoxicity. Toxicol Lett. 2022 Jun 15;363:11-26. doi: 10.1016/j.toxlet.2022.05.002. Epub 2022 May 18.
88 Sorafenib induces apoptosis specifically in cells expressing BCR/ABL by inhibiting its kinase activity to activate the intrinsic mitochondrial pathway. Cancer Res. 2009 May 1;69(9):3927-36. doi: 10.1158/0008-5472.CAN-08-2978. Epub 2009 Apr 14.
89 A high-throughput screen for teratogens using human pluripotent stem cells. Toxicol Sci. 2014 Jan;137(1):76-90. doi: 10.1093/toxsci/kft239. Epub 2013 Oct 23.
90 Denaturing-HPLC-based assay for detection of ABL mutations in chronic myeloid leukemia patients resistant to Imatinib. Clin Chem. 2004 Jul;50(7):1205-13. doi: 10.1373/clinchem.2004.031112. Epub 2004 Apr 23.
91 Identification of Genes That Modulate Susceptibility to Formaldehyde and Imatinib by Functional Genomic Screening in Human Haploid KBM7 Cells. Toxicol Sci. 2016 May;151(1):10-22. doi: 10.1093/toxsci/kfw032. Epub 2016 Mar 22.
92 Disruption of the inhibitor of apoptosis protein survivin sensitizes Bcr-abl-positive cells to STI571-induced apoptosis. Cancer Res. 2005 Sep 15;65(18):8224-32. doi: 10.1158/0008-5472.CAN-05-0303.
93 Epigenetic down-regulation of BIM expression is associated with reduced optimal responses to imatinib treatment in chronic myeloid leukaemia. Eur J Cancer. 2009 Jul;45(10):1877-89. doi: 10.1016/j.ejca.2009.04.005. Epub 2009 May 4.