General Information of Drug Combination (ID: DCT6EX8)

Drug Combination Name
Olanzapine Zileuton
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Olanzapine   DMPFN6Y Zileuton   DMVRIC2
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: 13.18
Bliss Independence Score: 13.18
Loewe Additivity Score: 28.23
LHighest Single Agent (HSA) Score: 28.23

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 [7]
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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 [8]
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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 [9]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [10]
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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 [11]
D(2) dopamine receptor (DRD2) OTBLXKEG DRD2_HUMAN Increases Response To Substance [12]
Lathosterol oxidase (SC5D) OT41KMW4 SC5D_HUMAN Increases Expression [13]
Low-density lipoprotein receptor (LDLR) OTH559LU LDLR_HUMAN Increases Expression [13]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) OTRT3F3U HMDH_HUMAN Increases Expression [13]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1) OTCO26FV HMCS1_HUMAN Increases Expression [13]
Long-chain fatty acid transport protein 2 (SLC27A2) OT7JEG5F S27A2_HUMAN Increases Expression [14]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [15]
Ceruloplasmin (CP) OTM8JE4Y CERU_HUMAN Affects Phosphorylation [16]
Prothrombin (F2) OTNFSM49 THRB_HUMAN Affects Phosphorylation [16]
Complement factor B (CFB) OTZITNEJ CFAB_HUMAN Affects Phosphorylation [16]
Alpha-1-antichymotrypsin (SERPINA3) OT9BP2S0 AACT_HUMAN Increases Phosphorylation [16]
Alpha-2-macroglobulin (A2M) OTFTX90K A2MG_HUMAN Affects Phosphorylation [16]
Complement C3 (C3) OTCH5GS0 CO3_HUMAN Affects Phosphorylation [16]
Complement C5 (C5) OTSL3OIC CO5_HUMAN Affects Phosphorylation [16]
Kininogen-1 (KNG1) OT4X9LDE KNG1_HUMAN Affects Phosphorylation [16]
Prolactin (PRL) OTWFQGX7 PRL_HUMAN Increases Expression [17]
Insulin (INS) OTZ85PDU INS_HUMAN Increases Expression [18]
Collagen alpha-1(I) chain (COL1A1) OTI31178 CO1A1_HUMAN Decreases Phosphorylation [16]
Apolipoprotein A-I (APOA1) OT5THARI APOA1_HUMAN Increases Phosphorylation [16]
Complement component C9 (C9) OT7I5FDX CO9_HUMAN Affects Phosphorylation [16]
Beta-2-glycoprotein 1 (APOH) OTFMUX6O APOH_HUMAN Affects Phosphorylation [16]
Fibronectin (FN1) OTB5ZN4Q FINC_HUMAN Affects Phosphorylation [16]
Albumin (ALB) OTVMM513 ALBU_HUMAN Affects Phosphorylation [16]
Vitamin D-binding protein (GC) OTWS63BY VTDB_HUMAN Affects Phosphorylation [16]
Hemopexin (HPX) OT14T7Q1 HEMO_HUMAN Affects Phosphorylation [16]
Apolipoprotein B-100 (APOB) OTH0UOCZ APOB_HUMAN Increases Phosphorylation [16]
Histidine-rich glycoprotein (HRG) OTPLUFOG HRG_HUMAN Affects Phosphorylation [16]
Alpha-1B-glycoprotein (A1BG) OTFVUGNQ A1BG_HUMAN Affects Phosphorylation [16]
Sex hormone-binding globulin (SHBG) OTPWU5IW SHBG_HUMAN Decreases Expression [19]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [20]
Plasma protease C1 inhibitor (SERPING1) OT6CVN45 IC1_HUMAN Affects Phosphorylation [16]
Apolipoprotein A-IV (APOA4) OT466POQ APOA4_HUMAN Affects Phosphorylation [16]
Fatty acid-binding protein, liver (FABP1) OTR34ETM FABPL_HUMAN Increases Expression [14]
Complement factor H (CFH) OTAGKQTJ CFAH_HUMAN Decreases Phosphorylation [16]
Complement C4-A (C4A) OTXMOYXU CO4A_HUMAN Decreases Phosphorylation [16]
Clusterin (CLU) OTQGG0JM CLUS_HUMAN Affects Phosphorylation [16]
Muscarinic acetylcholine receptor M1 (CHRM1) OTKW3E6B ACM1_HUMAN Affects Binding [21]
Complement component C6 (C6) OTCKR304 CO6_HUMAN Affects Phosphorylation [16]
Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4) OTJZG0LD GLUT4_HUMAN Increases Expression [22]
Inter-alpha-trypsin inhibitor heavy chain H2 (ITIH2) OTG3WBBE ITIH2_HUMAN Affects Phosphorylation [16]
Brain-derived neurotrophic factor (BDNF) OTLGH7EW BDNF_HUMAN Increases Expression [23]
5-hydroxytryptamine receptor 2A (HTR2A) OTWXJX0M 5HT2A_HUMAN Affects Binding [21]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Increases Expression [24]
Histamine H1 receptor (HRH1) OT8F9FV6 HRH1_HUMAN Affects Binding [21]
Leptin (LEP) OT5Q7ODW LEP_HUMAN Increases Expression [18]
Pituitary adenylate cyclase-activating polypeptide type I receptor (ADCYAP1R1) OTNBHULA PACR_HUMAN Affects Expression [6]
Afamin (AFM) OTPOR8IO AFAM_HUMAN Affects Phosphorylation [16]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Decreases Expression [24]
5-hydroxytryptamine receptor 6 (HTR6) OT8GTDDY 5HT6R_HUMAN Affects Binding [21]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [25]
Bcl-2-interacting killer (BIK) OTTH1T3D BIK_HUMAN Increases Expression [20]
Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) OT460OO1 ITIH4_HUMAN Affects Phosphorylation [16]
Long-chain fatty acid transport protein 5 (SLC27A5) OT4OK511 S27A5_HUMAN Increases Expression [14]
D(3) dopamine receptor (DRD3) OT0OFFKB DRD3_HUMAN Increases ADR [26]
5-hydroxytryptamine receptor 1A (HTR1A) OT38K9MK 5HT1A_HUMAN Increases Response [27]
5-hydroxytryptamine receptor 2C (HTR2C) OT6H8DE0 5HT2C_HUMAN Increases Response To Substance [28]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Increases Response To Substance [29]
Aquaporin-4 (AQP4) OTA9MYD5 AQP4_HUMAN Increases Response To Substance [30]
D(4) dopamine receptor (DRD4) OTAJTO7N DRD4_HUMAN Increases ADR [26]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases ADR [26]
Methylenetetrahydrofolate reductase (MTHFR) OTUBJSR7 MTHR_HUMAN Affects Response To Substance [31]
Synaptosomal-associated protein 25 (SNAP25) OTUIQ81Q SNP25_HUMAN Affects Response To Substance [32]
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⏷ Show the Full List of 63 DOT(s)
Indication(s) of Zileuton
Disease Entry ICD 11 Status REF
Allergic asthma CA23.0 Approved [4]
Asthma CA23 Approved [5]
Intrinsic asthma N.A. Approved [4]
Zileuton Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Arachidonate 5-lipoxygenase (5-LOX) TT2J34L LOX5_HUMAN Inhibitor [33]
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Zileuton Interacts with 5 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [34]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [35]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [36]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DE85D2P UD19_HUMAN Metabolism [34]
Prostaglandin G/H synthase 1 (COX-1) DE073H6 PGH1_HUMAN Metabolism [34]
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Zileuton Interacts with 8 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Decreases Activity [37]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Decreases Activity [38]
Polyunsaturated fatty acid 5-lipoxygenase (ALOX5) OT7FOIK2 LOX5_HUMAN Decreases Activity [39]
11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2) OTHF4H9U DHI2_HUMAN Increases Activity [39]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Secretion [40]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [41]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [41]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Affects Response To Substance [42]
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⏷ Show the Full List of 8 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 Olanzapine FDA Label
3 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: 47).
4 Zileuton FDA Label
5 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: 5297).
6 Neuroleptic Drugs and PACAP Differentially Affect the mRNA Expression of Genes Encoding PAC1/VPAC Type Receptors. Neurochem Res. 2017 Apr;42(4):943-952. doi: 10.1007/s11064-016-2127-2. Epub 2016 Nov 30.
7 Olanzapine: an updated review of its use in the management of schizophrenia. Drugs. 2001;61(1):111-61.
8 Identification of P-glycoprotein substrates and inhibitors among psychoactive compounds--implications for pharmacokinetics of selected substrates. J Pharm Pharmacol. 2004 Aug;56(8):967-75.
9 Interactions between the cytochrome P450 system and the second-generation antipsychotics. J Psychiatry Neurosci. 2003 Mar;28(2):99-112.
10 [Olanzapine: pharmacology, pharmacokinetics and therapeutic drug monitoring]. Fortschr Neurol Psychiatr. 2001 Nov;69(11):510-7.
11 Evaluation of antipsychotic drugs as inhibitors of multidrug resistance transporter P-glycoprotein. Psychopharmacology (Berl). 2006 Sep;187(4):415-23. doi: 10.1007/s00213-006-0437-9. Epub 2006 Jun 30.
12 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.
13 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.
14 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.
15 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.
16 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.
17 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.
18 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.
19 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.
20 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.
21 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.
22 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.
23 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.
24 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.
25 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.
26 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.
27 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.
28 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.
29 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.
30 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.
31 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.
32 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.
33 5-lipoxygenase inhibitor zileuton attenuates ischemic brain damage: involvement of matrix metalloproteinase 9. Neurol Res. 2009 Oct;31(8):848-52.
34 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.
35 Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218.
36 Identification of the human liver cytochrome P450 enzymes involved in the metabolism of zileuton (ABT-077) and its N-dehydroxylated metabolite, Abbott-66193. Drug Metab Dispos. 1995 Oct;23(10):1163-74.
37 Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity. Bioorg Med Chem Lett. 2004 Nov 15;14(22):5591-4.
38 Mechanism-based inhibition of human liver microsomal cytochrome P450 1A2 by zileuton, a 5-lipoxygenase inhibitor. Drug Metab Dispos. 2003 Nov;31(11):1352-60.
39 Prostaglandins and leukotriene B4 are potent inhibitors of 11beta-hydroxysteroid dehydrogenase type 2 activity in human choriocarcinoma JEG-3 cells. Biol Reprod. 1999 Jul;61(1):40-5.
40 Zileuton, a new efficient and safe systemic anti-acne drug. Dermatoendocrinol. 2009 May;1(3):188-92. doi: 10.4161/derm.1.3.8368.
41 Palmitate increases the susceptibility of cells to drug-induced toxicity: an in vitro method to identify drugs with potential contraindications in patients with metabolic disease. Toxicol Sci. 2012 Oct;129(2):346-62. doi: 10.1093/toxsci/kfs208. Epub 2012 Jun 14.
42 5-lipoxygenase pharmacogenetics in asthma: overlap with Cys-leukotriene receptor antagonist loci. Pharmacogenet Genomics. 2009 Mar;19(3):244-7. doi: 10.1097/FPC.0b013e328326e0b1.