Details of the Drug Combination

General Information of Drug Combination (ID: DCT6EX8)

• Drug Combination Name: Olanzapine + Zileuton
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Olanzapine (DMPFN6Y): Small molecular drug
  Zileuton (DMVRIC2): Small molecular drug
• 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

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]

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]

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]

Olanzapine Interacts with 36 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]
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]
Alpha-1-antichymotrypsin (SERPINA3)	OT9BP2S0	AACT_HUMAN	Increases Phosphorylation	[16]
Alpha-2-macroglobulin (A2M)	OTFTX90K	A2MG_HUMAN	Affects Phosphorylation	[16]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Decreases Phosphorylation	[16]
Complement component C9 (C9)	OT7I5FDX	CO9_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]
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	[17]
Plasma protease C1 inhibitor (SERPING1)	OT6CVN45	IC1_HUMAN	Affects Phosphorylation	[16]
Complement C4-A (C4A)	OTXMOYXU	CO4A_HUMAN	Decreases Phosphorylation	[16]
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	[18]
Inter-alpha-trypsin inhibitor heavy chain H2 (ITIH2)	OTG3WBBE	ITIH2_HUMAN	Affects Phosphorylation	[16]
5-hydroxytryptamine receptor 2A (HTR2A)	OTWXJX0M	5HT2A_HUMAN	Affects Binding	[19]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Increases Expression	[20]
Pituitary adenylate cyclase-activating polypeptide type I receptor (ADCYAP1R1)	OTNBHULA	PACR_HUMAN	Affects Expression	[6]
Afamin (AFM)	OTPOR8IO	AFAM_HUMAN	Affects Phosphorylation	[16]
5-hydroxytryptamine receptor 6 (HTR6)	OT8GTDDY	5HT6R_HUMAN	Affects Binding	[19]
Bcl-2-interacting killer (BIK)	OTTH1T3D	BIK_HUMAN	Increases Expression	[21]
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	[22]
5-hydroxytryptamine receptor 1A (HTR1A)	OT38K9MK	5HT1A_HUMAN	Increases Response	[23]
5-hydroxytryptamine receptor 2C (HTR2C)	OT6H8DE0	5HT2C_HUMAN	Increases Response To Substance	[24]
Aquaporin-4 (AQP4)	OTA9MYD5	AQP4_HUMAN	Increases Response To Substance	[25]
D(4) dopamine receptor (DRD4)	OTAJTO7N	DRD4_HUMAN	Increases ADR	[22]

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	[26]

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	[27]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[28]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[29]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Metabolism	[27]
Prostaglandin G/H synthase 1 (COX-1)	DE073H6	PGH1_HUMAN	Metabolism	[27]

References

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• [2] Olanzapine FDA Label
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• [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).
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• [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.
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• [19] 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.
• [20] 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.
• [21] 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.
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