General Information of Drug Combination (ID: DCE5I22)

Drug Combination Name
Olanzapine Triapine
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Olanzapine   DMPFN6Y Triapine   DM7XZY5
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: 2.62
Bliss Independence Score: 2.62
Loewe Additivity Score: 3.49
LHighest Single Agent (HSA) Score: 3.49

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Olanzapine
Disease Entry ICD 11 Status REF
Bipolar depression N.A. Approved [2]
Major depressive disorder 6A70.3 Approved [2]
Schizoaffective disorder 6A21 Approved [2]
Schizophrenia 6A20 Approved [3]
Olanzapine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Dopamine D2 receptor (D2R) TTEX248 DRD2_HUMAN Agonist [6]
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Olanzapine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]
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Olanzapine Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [8]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [9]
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Olanzapine Interacts with 63 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Activity [10]
D(2) dopamine receptor (DRD2) OTBLXKEG DRD2_HUMAN Increases Response To Substance [11]
Lathosterol oxidase (SC5D) OT41KMW4 SC5D_HUMAN Increases Expression [12]
Low-density lipoprotein receptor (LDLR) OTH559LU LDLR_HUMAN Increases Expression [12]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) OTRT3F3U HMDH_HUMAN Increases Expression [12]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1) OTCO26FV HMCS1_HUMAN Increases Expression [12]
Long-chain fatty acid transport protein 2 (SLC27A2) OT7JEG5F S27A2_HUMAN Increases Expression [13]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [14]
Ceruloplasmin (CP) OTM8JE4Y CERU_HUMAN Affects Phosphorylation [15]
Prothrombin (F2) OTNFSM49 THRB_HUMAN Affects Phosphorylation [15]
Complement factor B (CFB) OTZITNEJ CFAB_HUMAN Affects Phosphorylation [15]
Alpha-1-antichymotrypsin (SERPINA3) OT9BP2S0 AACT_HUMAN Increases Phosphorylation [15]
Alpha-2-macroglobulin (A2M) OTFTX90K A2MG_HUMAN Affects Phosphorylation [15]
Complement C3 (C3) OTCH5GS0 CO3_HUMAN Affects Phosphorylation [15]
Complement C5 (C5) OTSL3OIC CO5_HUMAN Affects Phosphorylation [15]
Kininogen-1 (KNG1) OT4X9LDE KNG1_HUMAN Affects Phosphorylation [15]
Prolactin (PRL) OTWFQGX7 PRL_HUMAN Increases Expression [16]
Insulin (INS) OTZ85PDU INS_HUMAN Increases Expression [17]
Collagen alpha-1(I) chain (COL1A1) OTI31178 CO1A1_HUMAN Decreases Phosphorylation [15]
Apolipoprotein A-I (APOA1) OT5THARI APOA1_HUMAN Increases Phosphorylation [15]
Complement component C9 (C9) OT7I5FDX CO9_HUMAN Affects Phosphorylation [15]
Beta-2-glycoprotein 1 (APOH) OTFMUX6O APOH_HUMAN Affects Phosphorylation [15]
Fibronectin (FN1) OTB5ZN4Q FINC_HUMAN Affects Phosphorylation [15]
Albumin (ALB) OTVMM513 ALBU_HUMAN Affects Phosphorylation [15]
Vitamin D-binding protein (GC) OTWS63BY VTDB_HUMAN Affects Phosphorylation [15]
Hemopexin (HPX) OT14T7Q1 HEMO_HUMAN Affects Phosphorylation [15]
Apolipoprotein B-100 (APOB) OTH0UOCZ APOB_HUMAN Increases Phosphorylation [15]
Histidine-rich glycoprotein (HRG) OTPLUFOG HRG_HUMAN Affects Phosphorylation [15]
Alpha-1B-glycoprotein (A1BG) OTFVUGNQ A1BG_HUMAN Affects Phosphorylation [15]
Sex hormone-binding globulin (SHBG) OTPWU5IW SHBG_HUMAN Decreases Expression [18]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [19]
Plasma protease C1 inhibitor (SERPING1) OT6CVN45 IC1_HUMAN Affects Phosphorylation [15]
Apolipoprotein A-IV (APOA4) OT466POQ APOA4_HUMAN Affects Phosphorylation [15]
Fatty acid-binding protein, liver (FABP1) OTR34ETM FABPL_HUMAN Increases Expression [13]
Complement factor H (CFH) OTAGKQTJ CFAH_HUMAN Decreases Phosphorylation [15]
Complement C4-A (C4A) OTXMOYXU CO4A_HUMAN Decreases Phosphorylation [15]
Clusterin (CLU) OTQGG0JM CLUS_HUMAN Affects Phosphorylation [15]
Muscarinic acetylcholine receptor M1 (CHRM1) OTKW3E6B ACM1_HUMAN Affects Binding [20]
Complement component C6 (C6) OTCKR304 CO6_HUMAN Affects Phosphorylation [15]
Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4) OTJZG0LD GLUT4_HUMAN Increases Expression [21]
Inter-alpha-trypsin inhibitor heavy chain H2 (ITIH2) OTG3WBBE ITIH2_HUMAN Affects Phosphorylation [15]
Brain-derived neurotrophic factor (BDNF) OTLGH7EW BDNF_HUMAN Increases Expression [22]
5-hydroxytryptamine receptor 2A (HTR2A) OTWXJX0M 5HT2A_HUMAN Affects Binding [20]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Increases Expression [23]
Histamine H1 receptor (HRH1) OT8F9FV6 HRH1_HUMAN Affects Binding [20]
Leptin (LEP) OT5Q7ODW LEP_HUMAN Increases Expression [17]
Pituitary adenylate cyclase-activating polypeptide type I receptor (ADCYAP1R1) OTNBHULA PACR_HUMAN Affects Expression [5]
Afamin (AFM) OTPOR8IO AFAM_HUMAN Affects Phosphorylation [15]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Decreases Expression [23]
5-hydroxytryptamine receptor 6 (HTR6) OT8GTDDY 5HT6R_HUMAN Affects Binding [20]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [24]
Bcl-2-interacting killer (BIK) OTTH1T3D BIK_HUMAN Increases Expression [19]
Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) OT460OO1 ITIH4_HUMAN Affects Phosphorylation [15]
Long-chain fatty acid transport protein 5 (SLC27A5) OT4OK511 S27A5_HUMAN Increases Expression [13]
D(3) dopamine receptor (DRD3) OT0OFFKB DRD3_HUMAN Increases ADR [25]
5-hydroxytryptamine receptor 1A (HTR1A) OT38K9MK 5HT1A_HUMAN Increases Response [26]
5-hydroxytryptamine receptor 2C (HTR2C) OT6H8DE0 5HT2C_HUMAN Increases Response To Substance [27]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Increases Response To Substance [28]
Aquaporin-4 (AQP4) OTA9MYD5 AQP4_HUMAN Increases Response To Substance [29]
D(4) dopamine receptor (DRD4) OTAJTO7N DRD4_HUMAN Increases ADR [25]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases ADR [25]
Methylenetetrahydrofolate reductase (MTHFR) OTUBJSR7 MTHR_HUMAN Affects Response To Substance [30]
Synaptosomal-associated protein 25 (SNAP25) OTUIQ81Q SNP25_HUMAN Affects Response To Substance [31]
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⏷ Show the Full List of 63 DOT(s)
Indication(s) of Triapine
Disease Entry ICD 11 Status REF
Nerve injury ND56.4 Phase 2 [4]
Triapine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Ribonucleoside-diphosphate reductase M2 (RRM2) TTBWDI0 RIR2_HUMAN Modulator [4]
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Triapine Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [33]
Thioredoxin-dependent peroxide reductase, mitochondrial (PRDX3) OTLB2WEU PRDX3_HUMAN Increases Oxidation [32]
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References

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2 Olanzapine FDA Label
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4 PAN-811 inhibits oxidative stress-induced cell death of human Alzheimer's disease-derived and age-matched olfactory neuroepithelial cells via suppression of intracellular reactive oxygen species. J Alzheimers Dis. 2009;17(3):611-9.
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8 Interactions between the cytochrome P450 system and the second-generation antipsychotics. J Psychiatry Neurosci. 2003 Mar;28(2):99-112.
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11 Dopamine receptor D2 gene is associated with weight gain in schizophrenic patients under long-term atypical antipsychotic treatment. Pharmacogenet Genomics. 2010 Jun;20(6):359-66. doi: 10.1097/FPC.0b013e3283397d06.
12 Drug-induced activation of SREBP-controlled lipogenic gene expression in CNS-related cell lines: marked differences between various antipsychotic drugs. BMC Neurosci. 2006 Oct 20;7:69.
13 Up-regulation of hepatic fatty acid transporters and inhibition/down-regulation of hepatic OCTN2 contribute to olanzapine-induced liver steatosis. Toxicol Lett. 2019 Nov;316:183-193. doi: 10.1016/j.toxlet.2019.08.013. Epub 2019 Aug 19.
14 In vitro approach to assess the potential for risk of idiosyncratic adverse reactions caused by candidate drugs. Chem Res Toxicol. 2012 Aug 20;25(8):1616-32. doi: 10.1021/tx300091x. Epub 2012 May 31.
15 Effects of olanzapine on serum protein phosphorylation patterns in patients with schizophrenia. Proteomics Clin Appl. 2015 Oct;9(9-10):907-16. doi: 10.1002/prca.201400148. Epub 2015 May 15.
16 The effects of olanzapine, risperidone, and haloperidol on plasma prolactin levels in patients with schizophrenia. Clin Ther. 2000 Sep;22(9):1085-96. doi: 10.1016/S0149-2918(00)80086-7.
17 Recovery from new-onset diabetes in a schizophrenic man after withdrawal of olanzapine. Psychosomatics. 2002 Jan-Feb;43(1):67-70. doi: 10.1176/appi.psy.43.1.67.
18 Hormonal markers of metabolic dysregulation in patients with severe mental disorders after olanzapine treatment under real-life conditions. J Clin Psychopharmacol. 2009 Apr;29(2):109-16. doi: 10.1097/JCP.0b013e31819b95fc.
19 Clozapine induces oxidative stress and proapoptotic gene expression in neutrophils of schizophrenic patients. J Clin Psychopharmacol. 2005 Oct;25(5):419-26. doi: 10.1097/01.jcp.0000177668.42640.fe.
20 No evidence for binding of clozapine, olanzapine and/or haloperidol to selected receptors involved in body weight regulation. Pharmacogenomics J. 2007 Aug;7(4):275-81. doi: 10.1038/sj.tpj.6500418. Epub 2006 Sep 19.
21 Effects of different antipsychotics and the antidepressant mirtazapine on glucose transporter mRNA levels in human blood cells. J Psychiatr Res. 2006 Jun;40(4):374-9. doi: 10.1016/j.jpsychires.2005.04.016. Epub 2005 Jul 5.
22 The differential effects of neuroleptic drugs and PACAP on the expression of BDNF mRNA and protein in a human glioblastoma cell line. Acta Neurobiol Exp (Wars). 2017;77(3):205-213.
23 Famotidine has a neuroprotective effect on MK-801 induced toxicity via the Akt/GSK-3/-catenin signaling pathway in the SH-SY5Y cell line. Chem Biol Interact. 2019 Dec 1;314:108823. doi: 10.1016/j.cbi.2019.108823. Epub 2019 Sep 26.
24 Effects of cyamemazine on hERG, INa, ICa, Ito, Isus and IK1 channel currents, and on the QTc interval in guinea pigs. Eur J Pharmacol. 2006 Feb 27;532(3):270-8. doi: 10.1016/j.ejphar.2005.12.079. Epub 2006 Feb 21.
25 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.
26 Serotonin-1A receptor gene polymorphism and the ability of antipsychotic drugs to improve attention in schizophrenia. Adv Ther. 2010 May;27(5):307-13. doi: 10.1007/s12325-010-0035-4. Epub 2010 Jun 8.
27 Olanzapine-induced weight gain is associated with the -759C/T and -697G/C polymorphisms of the HTR2C gene. Pharmacogenomics J. 2009 Aug;9(4):234-41. doi: 10.1038/tpj.2009.18. Epub 2009 May 12.
28 DRD2/AKT1 interaction on D2 c-AMP independent signaling, attentional processing, and response to olanzapine treatment in schizophrenia. Proc Natl Acad Sci U S A. 2011 Jan 18;108(3):1158-63. doi: 10.1073/pnas.1013535108. Epub 2010 Dec 27.
29 Different impacts of aquaporin 4 and MAOA allele variation among olanzapine, risperidone, and paliperidone in schizophrenia. J Clin Psychopharmacol. 2012 Jun;32(3):394-7. doi: 10.1097/JCP.0b013e31825370f4.
30 MTHFR and risk of metabolic syndrome in patients with schizophrenia. Schizophr Res. 2010 Aug;121(1-3):193-8. doi: 10.1016/j.schres.2010.05.030. Epub 2010 Jun 12.
31 The SNAP-25 gene may be associated with clinical response and weight gain in antipsychotic treatment of schizophrenia. Neurosci Lett. 2005 May 6;379(2):81-9. doi: 10.1016/j.neulet.2004.12.037. Epub 2005 Jan 26.
32 The iron-chelating drug triapine causes pronounced mitochondrial thiol redox stress. Toxicol Lett. 2011 Mar 5;201(2):130-6. doi: 10.1016/j.toxlet.2010.12.017. Epub 2010 Dec 31.
33 Distinct mechanisms of cell-kill by triapine and its terminally dimethylated derivative Dp44mT due to a loss or gain of activity of their copper(II) complexes. Biochem Pharmacol. 2014 Oct 1;91(3):312-22. doi: 10.1016/j.bcp.2014.08.006. Epub 2014 Aug 15.