Details of the Drug Combination

General Information of Drug Combination (ID: DCCDRIQ)

• Drug Combination Name: Dopamine + Gefitinib
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Dopamine (DMPGUCF): Small molecular drug
  Gefitinib (DM15F0X): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 5.14
  Bliss Independence Score: 5.14
  Loewe Additivity Score: 8.4
  LHighest Single Agent (HSA) Score: 8.4

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Dopamine

Disease Entry	ICD 11	Status	REF
Acromegaly	5A60.0	Approved	[2]
Carcinoid syndrome	5B10	Approved	[2]
Parkinson disease	8A00.0	Approved	[3]
Parkinsonian disorder	N.A.	Approved	[2]
Postencephalitic Parkinson disease	N.A.	Approved	[2]
Hypotension	BA20-BA21	Phase 1	[3]

Dopamine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Agonist	[9]

Dopamine Interacts with 6 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic cation transporter 2 (SLC22A2)	DT9IDPW	S22A2_HUMAN	Substrate	[10]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[11]
Vesicular amine transporter 2 (SLC18A2)	DTT7VPB	VMAT2_HUMAN	Substrate	[12]
Vesicular amine transporter 1 (SLC18A1)	DTM953D	VMAT1_HUMAN	Substrate	[12]
Synaptic vesicle glycoprotein 2C (SLC22B3)	DT7A9GF	SV2C_HUMAN	Substrate	[13]
Sodium-dependent dopamine transporter (SLC6A3)	DT3BA8L	SC6A3_HUMAN	Substrate	[14]

Dopamine Interacts with 8 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[15]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[16]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[16]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[16]
Catechol O-methyltransferase (COMT)	DEV3T4A	COMT_HUMAN	Metabolism	[17]
Monoamine oxidase type B (MAO-B)	DET2NXO	AOFB_HUMAN	Metabolism	[18]
Sulfotransferase 1B1 (SULT1B1)	DED5UR3	ST1B1_HUMAN	Metabolism	[19]
Dopamine dehydroxylase (dadH)	DEL0D64	DADH_EGGLN	Metabolism	[20]

Dopamine Interacts with 41 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Sodium-dependent dopamine transporter (SLC6A3)	OT39XG28	SC6A3_HUMAN	Increases Activity	[21]
Glial fibrillary acidic protein (GFAP)	OTQ01ZAS	GFAP_HUMAN	Increases ADR	[22]
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)	OT4SO7J4	BNIP3_HUMAN	Increases Expression	[23]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Increases Expression	[23]
POTE ankyrin domain family member F (POTEF)	OTV3WXYE	POTEF_HUMAN	Increases Expression	[6]
Citrate synthase, mitochondrial (CS)	OTYLYXMO	CISY_HUMAN	Increases Expression	[6]
ATP synthase subunit d, mitochondrial (ATP5PD)	OTAJDLE2	ATP5H_HUMAN	Increases Expression	[6]
Prelamin-A/C (LMNA)	OT3SG7ZR	LMNA_HUMAN	Increases Expression	[6]
Fructose-bisphosphate aldolase A (ALDOA)	OTWRFTIB	ALDOA_HUMAN	Increases Expression	[6]
ADP/ATP translocase 2 (SLC25A5)	OT1XIBMN	ADT2_HUMAN	Increases Expression	[6]
Heat shock protein HSP 90-beta (HSP90AB1)	OTR69EG7	HS90B_HUMAN	Increases Expression	[6]
Small ribosomal subunit protein uS2 (RPSA)	OTJZHEGT	RSSA_HUMAN	Increases Expression	[6]
POTE ankyrin domain family member I (POTEI)	OTST4AVP	POTEI_HUMAN	Decreases Expression	[6]
ADP/ATP translocase 3 (SLC25A6)	OT9KAJP7	ADT3_HUMAN	Increases Expression	[6]
Annexin A3 (ANXA3)	OTDD8OI7	ANXA3_HUMAN	Increases Expression	[6]
Histone H1.5 (H1-5)	OTAN7RD9	H15_HUMAN	Increases Expression	[6]
Heat shock 70 kDa protein 6 (HSPA6)	OTH4S7WB	HSP76_HUMAN	Increases Expression	[6]
Cofilin-1 (CFL1)	OTT6D5MH	COF1_HUMAN	Increases Expression	[6]
Thioredoxin-dependent peroxide reductase, mitochondrial (PRDX3)	OTLB2WEU	PRDX3_HUMAN	Increases Expression	[6]
Protein disulfide-isomerase A3 (PDIA3)	OTHPQ0Q3	PDIA3_HUMAN	Decreases Expression	[6]
Serine hydroxymethyltransferase, mitochondrial (SHMT2)	OT5NCAZN	GLYM_HUMAN	Increases Expression	[6]
Stress-70 protein, mitochondrial (HSPA9)	OT4TMVS9	GRP75_HUMAN	Increases Expression	[6]
Actin, cytoplasmic 1 (ACTB)	OT1MCP2F	ACTB_HUMAN	Affects Expression	[6]
Small ribosomal subunit protein RACK1 (RACK1)	OTZBCQ1U	RACK1_HUMAN	Increases Expression	[6]
Elongation factor 1-alpha 1 (EEF1A1)	OT00THXS	EF1A1_HUMAN	Increases Expression	[6]
Single-stranded DNA-binding protein, mitochondrial (SSBP1)	OTH2PZWH	SSBP_HUMAN	Increases Expression	[6]
Complement component 1 Q subcomponent-binding protein, mitochondrial (C1QBP)	OTPYQX3K	C1QBP_HUMAN	Increases Expression	[6]
Beta-actin-like protein 2 (ACTBL2)	OTD6B81U	ACTBL_HUMAN	Decreases Expression	[6]
5'-3' exonuclease PLD3 (PLD3)	OTL07SP2	PLD3_HUMAN	Affects Expression	[6]
Septin-9 (SEPTIN9)	OT1VMRFQ	SEPT9_HUMAN	Decreases Expression	[6]
RuvB-like 1 (RUVBL1)	OTWV19L7	RUVB1_HUMAN	Increases Expression	[6]
E3 ubiquitin-protein ligase parkin (PRKN)	OTJBN41W	PRKN_HUMAN	Increases Expression	[24]
Brain mitochondrial carrier protein 1 (SLC25A14)	OT1ZQSKS	UCP5_HUMAN	Increases Expression	[25]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Phosphorylation	[26]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[26]
D(1A) dopamine receptor (DRD1)	OTLZPBT7	DRD1_HUMAN	Increases Activity	[27]
Protein-L-isoaspartate(D-aspartate) O-methyltransferase (PCMT1)	OTGYVSGU	PIMT_HUMAN	Decreases Expression	[28]
Alpha-synuclein (SNCA)	OTPWC1MR	SYUA_HUMAN	Increases Response To Substance	[29]
Solute carrier family 22 member 3 (SLC22A3)	OTQYGVXX	S22A3_HUMAN	Increases Uptake	[30]
Secretin (SCT)	OTV3MLOO	SECR_HUMAN	Increases Metabolism	[31]
Equilibrative nucleoside transporter 4 (SLC29A4)	OTWTZXMX	S29A4_HUMAN	Increases Uptake	[30]

Indication(s) of Gefitinib

Disease Entry	ICD 11	Status	REF
Colon adenocarcinoma	N.A.	Approved	[4]
Glioblastoma	2A00	Approved	[4]
Lung cancer	2C25.0	Approved	[4]
Non-small-cell lung cancer	2C25.Y	Approved	[4]
Rectal adenocarcinoma	2B92	Approved	[4]
Rectum mucinous adenocarcinoma	N.A.	Approved	[4]
Solid tumour/cancer	2A00-2F9Z	Approved	[5]
Head and neck cancer	2D42	Phase 3	[5]
Urethral cancer	2C93	Phase 2	[5]
Colon cancer	2B90.Z	Investigative	[4]
Colon mucinous adenocarcinoma	N.A.	Investigative	[4]

Gefitinib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Inhibitor	[37]

Gefitinib Interacts with 4 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[38]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[39]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[40]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[40]

Gefitinib Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[41]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[42]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[41]

Gefitinib Interacts with 64 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 ADR	[43]
Sulfhydryl oxidase 1 (QSOX1)	OT4ZPK4P	QSOX1_HUMAN	Increases Expression	[44]
Growth arrest and DNA damage-inducible protein GADD45 gamma (GADD45G)	OT8V1J4M	GA45G_HUMAN	Decreases Expression	[44]
Interferon alpha-inducible protein 6 (IFI6)	OTWOOAM4	IFI6_HUMAN	Decreases Expression	[44]
Fibroblast growth factor 6 (FGF6)	OTRJ679P	FGF6_HUMAN	Increases Expression	[44]
Ski oncogene (SKI)	OT4KJ8F6	SKI_HUMAN	Increases Expression	[44]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Decreases Expression	[44]
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B)	OTDS2EAR	TNR1B_HUMAN	Decreases Expression	[44]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A)	OTDRV63V	GA45A_HUMAN	Increases Expression	[44]
Replication protein A 70 kDa DNA-binding subunit (RPA1)	OT76POLP	RFA1_HUMAN	Increases Expression	[44]
Adenosine receptor A1 (ADORA1)	OTI7X39E	AA1R_HUMAN	Decreases Expression	[44]
14-3-3 protein sigma (SFN)	OTLJCZ1U	1433S_HUMAN	Decreases Expression	[44]
Glycine--tRNA ligase (GARS1)	OT5B6R9Y	GARS_HUMAN	Increases Expression	[44]
Epidermal growth factor receptor substrate 15 (EPS15)	OT7NPP8U	EPS15_HUMAN	Increases Expression	[44]
Neural retina-specific leucine zipper protein (NRL)	OT65MFKQ	NRL_HUMAN	Decreases Expression	[44]
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (GNB2)	OT3JPRCQ	GBB2_HUMAN	Decreases Expression	[44]
Retinal guanylyl cyclase 1 (GUCY2D)	OT81UJI0	GUC2D_HUMAN	Decreases Expression	[44]
Cell growth regulator with RING finger domain protein 1 (CGRRF1)	OTLMNRCL	CGRF1_HUMAN	Increases Expression	[44]
Dual specificity protein phosphatase 9 (DUSP9)	OTZZWEQL	DUS9_HUMAN	Decreases Expression	[44]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[45]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Expression	[46]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[47]
Ubiquitin-like modifier-activating enzyme ATG7 (ATG7)	OTVT4YA1	ATG7_HUMAN	Increases Expression	[48]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[49]
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Decreases Phosphorylation	[50]
HLA class II histocompatibility antigen, DO alpha chain (HLA-DOA)	OTZE5Q7R	DOA_HUMAN	Affects Expression	[51]
Heat shock protein HSP 90-alpha (HSP90AA1)	OTLG1WPK	HS90A_HUMAN	Increases Secretion	[52]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[53]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Secretion	[54]
DnaJ homolog subfamily B member 1 (DNAJB1)	OTCOSEVH	DNJB1_HUMAN	Increases Secretion	[52]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Expression	[55]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Expression	[55]
G1/S-specific cyclin-D3 (CCND3)	OTNKPQ22	CCND3_HUMAN	Decreases Expression	[56]
HLA class I histocompatibility antigen, alpha chain F (HLA-F)	OT76CM19	HLAF_HUMAN	Affects Expression	[51]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Decreases Expression	[47]
Cyclin-dependent kinase 4 inhibitor B (CDKN2B)	OTAG24N1	CDN2B_HUMAN	Increases Expression	[49]
Mitogen-activated protein kinase 8 (MAPK8)	OTEREYS5	MK08_HUMAN	Decreases Phosphorylation	[33]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[56]
Tumor necrosis factor ligand superfamily member 6 (FASLG)	OTZARCHH	TNFL6_HUMAN	Increases Response To Substance	[57]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Affects Localization	[53]
Transcription factor E2F1 (E2F1)	OTLKYBBC	E2F1_HUMAN	Decreases Expression	[58]
Kelch-like ECH-associated protein 1 (KEAP1)	OTFHOD0C	KEAP1_HUMAN	Increases Expression	[59]
MHC class I polypeptide-related sequence B (MICB)	OTS2DVDW	MICB_HUMAN	Increases Expression	[60]
MHC class I polypeptide-related sequence A (MICA)	OTPEIEAR	MICA_HUMAN	Increases Expression	[60]
Major histocompatibility complex class I-related gene protein (MR1)	OTZU3XX7	HMR1_HUMAN	Affects Expression	[51]
Autophagy protein 5 (ATG5)	OT4T5SMS	ATG5_HUMAN	Increases Expression	[48]
Transcription factor SOX-17 (SOX17)	OT9H4WWE	SOX17_HUMAN	Decreases Localization	[61]
MARVEL domain-containing protein 1 (MARVELD1)	OT5CPOJE	MALD1_HUMAN	Decreases Response To Substance	[62]
Zinc finger protein SNAI2 (SNAI2)	OT7Y8EJ2	SNAI2_HUMAN	Affects Response To Substance	[63]
Membrane-associated progesterone receptor component 1 (PGRMC1)	OTBE6WAC	PGRC1_HUMAN	Decreases Response To Substance	[64]
RNA-binding protein 7 (RBM7)	OTFIWTMF	RBM7_HUMAN	Affects Response To Substance	[65]
Cell death regulator Aven (AVEN)	OTGIN5YK	AVEN_HUMAN	Affects Response To Substance	[65]
Forkhead box protein O3 (FOXO3)	OTHXQG4P	FOXO3_HUMAN	Increases Response To Substance	[66]
Phospholipase B-like 1 (PLBD1)	OTHYEB4W	PLBL1_HUMAN	Affects Response To Substance	[65]
Securin (PTTG1)	OTIMYS4W	PTTG1_HUMAN	Decreases Response To Substance	[53]
Pleckstrin homology-like domain family A member 2 (PHLDA2)	OTMV9DPP	PHLA2_HUMAN	Affects Response To Substance	[65]
DNA excision repair protein ERCC-1 (ERCC1)	OTNPYQHI	ERCC1_HUMAN	Affects Response To Substance	[36]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Response To Substance	[67]
Ceramide transfer protein (CERT1)	OTNUCNHX	CERT_HUMAN	Affects Response To Substance	[65]
Dual specificity protein phosphatase 3 (DUSP3)	OTPJX9B4	DUS3_HUMAN	Affects Response To Substance	[65]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Decreases Response To Substance	[68]
Pericentrin (PCNT)	OTW4Z65J	PCNT_HUMAN	Decreases Response To Substance	[64]
Coronin-1C (CORO1C)	OTXDF9T3	COR1C_HUMAN	Affects Response To Substance	[65]
Ribonucleoside-diphosphate reductase large subunit (RRM1)	OTXGQOR9	RIR1_HUMAN	Affects Response To Substance	[36]

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