Details of the Drug Combination

General Information of Drug Combination (ID: DCVOFGS)

• Drug Combination Name: Olanzapine + Imatinib
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Olanzapine (DMPFN6Y): Small molecular drug
  Imatinib (DM7RJXL): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 2.94
  Bliss Independence Score: 2.94
  Loewe Additivity Score: 4.62
  LHighest Single Agent (HSA) Score: 4.68

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	[12]

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	[13]

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	[14]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[15]

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	[16]
D(2) dopamine receptor (DRD2)	OTBLXKEG	DRD2_HUMAN	Increases Response To Substance	[17]
Lathosterol oxidase (SC5D)	OT41KMW4	SC5D_HUMAN	Increases Expression	[18]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1)	OTCO26FV	HMCS1_HUMAN	Increases Expression	[18]
Long-chain fatty acid transport protein 2 (SLC27A2)	OT7JEG5F	S27A2_HUMAN	Increases Expression	[19]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[20]
Ceruloplasmin (CP)	OTM8JE4Y	CERU_HUMAN	Affects Phosphorylation	[21]
Prothrombin (F2)	OTNFSM49	THRB_HUMAN	Affects Phosphorylation	[21]
Alpha-1-antichymotrypsin (SERPINA3)	OT9BP2S0	AACT_HUMAN	Increases Phosphorylation	[21]
Alpha-2-macroglobulin (A2M)	OTFTX90K	A2MG_HUMAN	Affects Phosphorylation	[21]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Decreases Phosphorylation	[21]
Complement component C9 (C9)	OT7I5FDX	CO9_HUMAN	Affects Phosphorylation	[21]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Phosphorylation	[21]
Vitamin D-binding protein (GC)	OTWS63BY	VTDB_HUMAN	Affects Phosphorylation	[21]
Hemopexin (HPX)	OT14T7Q1	HEMO_HUMAN	Affects Phosphorylation	[21]
Histidine-rich glycoprotein (HRG)	OTPLUFOG	HRG_HUMAN	Affects Phosphorylation	[21]
Alpha-1B-glycoprotein (A1BG)	OTFVUGNQ	A1BG_HUMAN	Affects Phosphorylation	[21]
Sex hormone-binding globulin (SHBG)	OTPWU5IW	SHBG_HUMAN	Decreases Expression	[22]
Plasma protease C1 inhibitor (SERPING1)	OT6CVN45	IC1_HUMAN	Affects Phosphorylation	[21]
Complement C4-A (C4A)	OTXMOYXU	CO4A_HUMAN	Decreases Phosphorylation	[21]
Complement component C6 (C6)	OTCKR304	CO6_HUMAN	Affects Phosphorylation	[21]
Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4)	OTJZG0LD	GLUT4_HUMAN	Increases Expression	[23]
Inter-alpha-trypsin inhibitor heavy chain H2 (ITIH2)	OTG3WBBE	ITIH2_HUMAN	Affects Phosphorylation	[21]
5-hydroxytryptamine receptor 2A (HTR2A)	OTWXJX0M	5HT2A_HUMAN	Affects Binding	[24]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Increases Expression	[25]
Pituitary adenylate cyclase-activating polypeptide type I receptor (ADCYAP1R1)	OTNBHULA	PACR_HUMAN	Affects Expression	[11]
Afamin (AFM)	OTPOR8IO	AFAM_HUMAN	Affects Phosphorylation	[21]
5-hydroxytryptamine receptor 6 (HTR6)	OT8GTDDY	5HT6R_HUMAN	Affects Binding	[24]
Bcl-2-interacting killer (BIK)	OTTH1T3D	BIK_HUMAN	Increases Expression	[26]
Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4)	OT460OO1	ITIH4_HUMAN	Affects Phosphorylation	[21]
Long-chain fatty acid transport protein 5 (SLC27A5)	OT4OK511	S27A5_HUMAN	Increases Expression	[19]
D(3) dopamine receptor (DRD3)	OT0OFFKB	DRD3_HUMAN	Increases ADR	[27]
5-hydroxytryptamine receptor 1A (HTR1A)	OT38K9MK	5HT1A_HUMAN	Increases Response	[28]
5-hydroxytryptamine receptor 2C (HTR2C)	OT6H8DE0	5HT2C_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	[27]

Indication(s) of Imatinib

Disease Entry	ICD 11	Status	REF
Acute lymphoblastic leukaemia	2A85	Approved	[4]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	N.A.	Approved	[5]
Choroidal neovascularization	9B76	Approved	[5]
Chronic eosinophilic leukemia	N.A.	Approved	[5]
Chronic myelogenous leukaemia	2A20.0	Approved	[6]
Chronic myeloid leukaemia	2A20	Approved	[7]
Dermatofibrosarcoma protuberans	N.A.	Approved	[5]
Gastrointestinal stromal tumour	2B5B	Approved	[5]
Leukemia	N.A.	Approved	[5]
Malignant peripheral nerve sheath tumor	N.A.	Approved	[5]
Myeloproliferative neoplasm	2A20	Approved	[5]
Pulmonary hypertension	BB01	Approved	[5]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[8]
Intestinal cancer	2C0Z	Phase 3	[6]
Lung cancer	2C25.0	Phase 2	[6]
Idiopathic hypereosinophilic syndrome	N.A.	Investigative	[5]
Middle East Respiratory Syndrome (MERS)	1D64	Investigative	[9]
Scleroderma	4A42	Investigative	[5]
Severe acute respiratory syndrome (SARS)	1D65	Investigative	[9]
Systemic mastocytosis	2A21.0	Investigative	[10]

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	.	[10]
Fusion protein Bcr-Abl (Bcr-Abl)	TTS7G69	BCR_HUMAN-ABL1_HUMAN	Inhibitor	[34]
Platelet-derived growth factor receptor (PDGFR)	TTI2WET	NOUNIPROTAC	Inhibitor	[34]
Tyrosine-protein kinase Kit (KIT)	TTX41N9	KIT_HUMAN	Inhibitor	[34]
HUMAN fusion protein Bcr-Abl (Bcr-Abl)	TTE63HY	BCR_HUMAN/ABL1_HUMAN	Inhibitor	[9]

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	[35]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[36]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[37]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[38]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[39]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[37]

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	[40]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[41]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[42]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[43]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[44]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[45]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[46]
Prostaglandin G/H synthase 1 (COX-1)	DE073H6	PGH1_HUMAN	Metabolism	[42]

Imatinib Interacts with 48 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Increases Expression	[47]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[47]
Aldehyde dehydrogenase, mitochondrial (ALDH2)	OTKJ9I3N	ALDH2_HUMAN	Decreases Expression	[48]
Eukaryotic translation initiation factor 4E (EIF4E)	OTDAWNLA	IF4E_HUMAN	Decreases Expression	[48]
Fructose-bisphosphate aldolase C (ALDOC)	OTEC13I5	ALDOC_HUMAN	Decreases Expression	[48]
Pyruvate dehydrogenase E1 component subunit beta, mitochondrial (PDHB)	OT2NHE5E	ODPB_HUMAN	Decreases Expression	[48]
Eukaryotic translation initiation factor 4B (EIF4B)	OTE8TXA8	IF4B_HUMAN	Decreases Expression	[48]
Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1)	OT5BZ1J9	P85A_HUMAN	Decreases Expression	[48]
G1/S-specific cyclin-D3 (CCND3)	OTNKPQ22	CCND3_HUMAN	Decreases Expression	[48]
Hexokinase-4 (GCK)	OTR3Q0NN	HXK4_HUMAN	Decreases Expression	[48]
Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform (PPP2CA)	OT83PT85	PP2AA_HUMAN	Increases Expression	[48]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[49]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[50]
Autophagy-related protein 13 (ATG13)	OTYMHNEJ	ATG13_HUMAN	Increases Phosphorylation	[31]
Keratin, type I cytoskeletal 14 (KRT14)	OTUVZ1DW	K1C14_HUMAN	Increases Expression	[51]
Heat shock protein beta-1 (HSPB1)	OTHFZ8ED	HSPB1_HUMAN	Increases Expression	[50]
Tyrosine-protein kinase Lck (LCK)	OT883FG9	LCK_HUMAN	Decreases Phosphorylation	[52]
ATP-dependent 6-phosphofructokinase, muscle type (PFKM)	OT1QY9JM	PFKAM_HUMAN	Decreases Expression	[53]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[54]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[50]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)	OTA675TJ	GTR1_HUMAN	Decreases Expression	[55]
Keratin, type II cytoskeletal 5 (KRT5)	OTVGI9HT	K2C5_HUMAN	Increases Expression	[51]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[56]
Transcription factor EB (TFEB)	OTJUJJQY	TFEB_HUMAN	Affects Localization	[31]
Insulin-like growth factor-binding protein 4 (IGFBP4)	OT2HZRBD	IBP4_HUMAN	Increases Expression	[50]
Interleukin-4 receptor subunit alpha (IL4R)	OTTXOTCW	IL4RA_HUMAN	Increases Expression	[50]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[52]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[52]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Decreases Expression	[57]
Crk-like protein (CRKL)	OTOYSD1R	CRKL_HUMAN	Decreases Phosphorylation	[58]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[31]
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Increases Expression	[50]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Decreases Expression	[57]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[59]
Nuclear receptor subfamily 0 group B member 2 (NR0B2)	OT7UVICX	NR0B2_HUMAN	Increases Expression	[60]
NGFI-A-binding protein 2 (NAB2)	OTG4BDF3	NAB2_HUMAN	Increases Expression	[50]
TRAF family member-associated NF-kappa-B activator (TANK)	OTZSGFIK	TANK_HUMAN	Increases Expression	[50]
NACHT, LRR and PYD domains-containing protein 3 (NLRP3)	OTZM6MHU	NLRP3_HUMAN	Increases Expression	[61]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Increases Activity	[60]
Docking protein 1 (DOK1)	OTGVRLW6	DOK1_HUMAN	Decreases Phosphorylation	[62]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B)	OTUYHB84	MLP3B_HUMAN	Increases Expression	[31]
Transcription factor SOX-17 (SOX17)	OT9H4WWE	SOX17_HUMAN	Decreases Localization	[63]
V-type proton ATPase subunit H (ATP6V1H)	OTX17GQ9	VATH_HUMAN	Increases Expression	[31]
LYR motif-containing protein 9 (LYRM9)	OT1MILTK	LYRM9_HUMAN	Affects Response To Substance	[64]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Response To Substance	[65]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Response To Substance	[66]
Tyrosine-protein kinase Lyn (LYN)	OTP686K2	LYN_HUMAN	Decreases Response To Substance	[58]
Serine/threonine-protein kinase PLK1 (PLK1)	OTRZX45T	PLK1_HUMAN	Increases Response To Substance	[54]

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