Details of the Drug Combination

General Information of Drug Combination (ID: DCC89TF)

• Drug Combination Name: Olanzapine + Arfolitixorin
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Olanzapine (DMPFN6Y): Small molecular drug
  Arfolitixorin (DMIXMYK): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 6.82
  Bliss Independence Score: 6.82
  Loewe Additivity Score: 8.97
  LHighest Single Agent (HSA) Score: 9.03

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	[6]

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]

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]

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]

Indication(s) of Arfolitixorin

Disease Entry	ICD 11	Status	REF
Colorectal cancer	2B91.Z	Phase 3	[4]

References

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• [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] ClinicalTrials.gov (NCT03750786) A Study to Compare the Efficacy of Arfolitixorin Versus Leucovorin in Combination With 5 Fluorouracil, Oxaliplatin, and Bevacizumab in Patients With Advanced Colorectal Cancer (AGENT). U.S. National Institutes of Health.
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