Details of the Drug Combination

General Information of Drug Combination (ID: DCVEQ08)

• Drug Combination Name: Dopamine + Metyrosine
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Dopamine (DMPGUCF): Small molecular drug
  Metyrosine (DMBYCU0): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 7.68
  Bliss Independence Score: 7.68
  Loewe Additivity Score: 10.29
  LHighest Single Agent (HSA) Score: 10.29

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	[8]

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	[9]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[10]
Vesicular amine transporter 2 (SLC18A2)	DTT7VPB	VMAT2_HUMAN	Substrate	[11]
Vesicular amine transporter 1 (SLC18A1)	DTM953D	VMAT1_HUMAN	Substrate	[11]
Synaptic vesicle glycoprotein 2C (SLC22B3)	DT7A9GF	SV2C_HUMAN	Substrate	[12]
Sodium-dependent dopamine transporter (SLC6A3)	DT3BA8L	SC6A3_HUMAN	Substrate	[13]

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	[14]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[15]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[15]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[15]
Catechol O-methyltransferase (COMT)	DEV3T4A	COMT_HUMAN	Metabolism	[16]
Monoamine oxidase type B (MAO-B)	DET2NXO	AOFB_HUMAN	Metabolism	[17]
Sulfotransferase 1B1 (SULT1B1)	DED5UR3	ST1B1_HUMAN	Metabolism	[18]
Dopamine dehydroxylase (dadH)	DEL0D64	DADH_EGGLN	Metabolism	[19]

Dopamine Interacts with 76 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Increases Abundance	[20]
Amine oxidase B (MAOB)	OTTDFM1O	AOFB_HUMAN	Decreases Amination	[21]
Catechol O-methyltransferase (COMT)	OTPWKTQG	COMT_HUMAN	Increases Methylation	[22]
Sodium-dependent dopamine transporter (SLC6A3)	OT39XG28	SC6A3_HUMAN	Increases Activity	[23]
Synaptic vesicular amine transporter (SLC18A2)	OTUOMMM6	VMAT2_HUMAN	Decreases Activity	[24]
Glial fibrillary acidic protein (GFAP)	OTQ01ZAS	GFAP_HUMAN	Increases ADR	[25]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[26]
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)	OT4SO7J4	BNIP3_HUMAN	Increases Expression	[26]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Increases Expression	[26]
Glutathione S-transferase A1 (GSTA1)	OTA7K5XA	GSTA1_HUMAN	Decreases Activity	[27]
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Decreases Activity	[27]
Glutathione S-transferase Mu 1 (GSTM1)	OTSBF2MO	GSTM1_HUMAN	Decreases Activity	[27]
Methionine synthase (MTR)	OTF2K2TA	METH_HUMAN	Increases Activity	[28]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Decreases Activity	[29]
POTE ankyrin domain family member F (POTEF)	OTV3WXYE	POTEF_HUMAN	Increases Expression	[5]
Citrate synthase, mitochondrial (CS)	OTYLYXMO	CISY_HUMAN	Increases Expression	[5]
ATP synthase subunit d, mitochondrial (ATP5PD)	OTAJDLE2	ATP5H_HUMAN	Increases Expression	[5]
Prelamin-A/C (LMNA)	OT3SG7ZR	LMNA_HUMAN	Increases Expression	[5]
Fructose-bisphosphate aldolase A (ALDOA)	OTWRFTIB	ALDOA_HUMAN	Increases Expression	[5]
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)	OTBPMIMW	G3P_HUMAN	Increases Expression	[5]
ADP/ATP translocase 2 (SLC25A5)	OT1XIBMN	ADT2_HUMAN	Increases Expression	[5]
Cathepsin D (CTSD)	OTQZ36F3	CATD_HUMAN	Increases Expression	[5]
Heat shock protein HSP 90-beta (HSP90AB1)	OTR69EG7	HS90B_HUMAN	Increases Expression	[5]
Small ribosomal subunit protein uS2 (RPSA)	OTJZHEGT	RSSA_HUMAN	Increases Expression	[5]
POTE ankyrin domain family member I (POTEI)	OTST4AVP	POTEI_HUMAN	Decreases Expression	[5]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Increases Expression	[5]
ADP/ATP translocase 3 (SLC25A6)	OT9KAJP7	ADT3_HUMAN	Increases Expression	[5]
Annexin A3 (ANXA3)	OTDD8OI7	ANXA3_HUMAN	Increases Expression	[5]
Pyruvate kinase PKM (PKM)	OTLHHMC2	KPYM_HUMAN	Increases Expression	[5]
Endoplasmin (HSP90B1)	OT02XLBR	ENPL_HUMAN	Increases Expression	[5]
Histone H1.5 (H1-5)	OTAN7RD9	H15_HUMAN	Increases Expression	[5]
Heat shock 70 kDa protein 6 (HSPA6)	OTH4S7WB	HSP76_HUMAN	Increases Expression	[5]
Nucleolin (NCL)	OTBXPKMP	NUCL_HUMAN	Increases Expression	[5]
Cofilin-1 (CFL1)	OTT6D5MH	COF1_HUMAN	Increases Expression	[5]
Myristoylated alanine-rich C-kinase substrate (MARCKS)	OT7N056G	MARCS_HUMAN	Increases Expression	[5]
Thioredoxin-dependent peroxide reductase, mitochondrial (PRDX3)	OTLB2WEU	PRDX3_HUMAN	Increases Expression	[5]
Protein disulfide-isomerase A3 (PDIA3)	OTHPQ0Q3	PDIA3_HUMAN	Decreases Expression	[5]
Serine hydroxymethyltransferase, mitochondrial (SHMT2)	OT5NCAZN	GLYM_HUMAN	Increases Expression	[5]
Prohibitin 1 (PHB1)	OTZNXYS2	PHB1_HUMAN	Increases Expression	[5]
Stress-70 protein, mitochondrial (HSPA9)	OT4TMVS9	GRP75_HUMAN	Increases Expression	[5]
Actin, cytoplasmic 1 (ACTB)	OT1MCP2F	ACTB_HUMAN	Affects Expression	[5]
Small ribosomal subunit protein RACK1 (RACK1)	OTZBCQ1U	RACK1_HUMAN	Increases Expression	[5]
Elongation factor 1-alpha 1 (EEF1A1)	OT00THXS	EF1A1_HUMAN	Increases Expression	[5]
Single-stranded DNA-binding protein, mitochondrial (SSBP1)	OTH2PZWH	SSBP_HUMAN	Increases Expression	[5]
Complement component 1 Q subcomponent-binding protein, mitochondrial (C1QBP)	OTPYQX3K	C1QBP_HUMAN	Increases Expression	[5]
Beta-actin-like protein 2 (ACTBL2)	OTD6B81U	ACTBL_HUMAN	Decreases Expression	[5]
5'-3' exonuclease PLD3 (PLD3)	OTL07SP2	PLD3_HUMAN	Affects Expression	[5]
Septin-9 (SEPTIN9)	OT1VMRFQ	SEPT9_HUMAN	Decreases Expression	[5]
RuvB-like 1 (RUVBL1)	OTWV19L7	RUVB1_HUMAN	Increases Expression	[5]
E3 ubiquitin-protein ligase parkin (PRKN)	OTJBN41W	PRKN_HUMAN	Increases Expression	[30]
Brain mitochondrial carrier protein 1 (SLC25A14)	OT1ZQSKS	UCP5_HUMAN	Increases Expression	[31]
Superoxide dismutase (SOD1)	OT39TA1L	SODC_HUMAN	Affects Binding	[32]
Prolactin (PRL)	OTWFQGX7	PRL_HUMAN	Decreases Expression	[33]
Insulin (INS)	OTZ85PDU	INS_HUMAN	Increases Expression	[34]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Phosphorylation	[35]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[35]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[36]
D(1A) dopamine receptor (DRD1)	OTLZPBT7	DRD1_HUMAN	Increases Activity	[37]
Protein-L-isoaspartate(D-aspartate) O-methyltransferase (PCMT1)	OTGYVSGU	PIMT_HUMAN	Decreases Expression	[38]
Ribosomal protein S6 kinase beta-1 (RPS6KB1)	OTAELNGX	KS6B1_HUMAN	Decreases Phosphorylation	[26]
Serine/threonine-protein kinase mTOR (MTOR)	OTHH8KU7	MTOR_HUMAN	Decreases Phosphorylation	[26]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[26]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[26]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Decreases Expression	[26]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Expression	[26]
Sulfotransferase 1A1 (SULT1A1)	OT0K7JIE	ST1A1_HUMAN	Increases Metabolism	[39]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Uptake	[40]
Tyrosine 3-monooxygenase (TH)	OT6ZORKP	TY3H_HUMAN	Increases Chemical Synthesis	[41]
Amine oxidase A (MAOA)	OT8NIWMQ	AOFA_HUMAN	Decreases Amination	[21]
Sulfotransferase 1A3 (SULT1A4)	OTHJ8WWV	ST1A3_HUMAN	Increases Metabolism	[39]
Alpha-synuclein (SNCA)	OTPWC1MR	SYUA_HUMAN	Increases Response To Substance	[42]
Neuron-specific vesicular protein calcyon (CALY)	OTQ7EMPU	CALY_HUMAN	Decreases Secretion	[43]
Solute carrier family 22 member 3 (SLC22A3)	OTQYGVXX	S22A3_HUMAN	Increases Uptake	[44]
Secretin (SCT)	OTV3MLOO	SECR_HUMAN	Increases Metabolism	[45]
Equilibrative nucleoside transporter 4 (SLC29A4)	OTWTZXMX	S29A4_HUMAN	Increases Uptake	[44]
GDP-mannose 4,6 dehydratase (GMDS)	OTWV79YD	GMDS_HUMAN	Increases ADR	[7]

Indication(s) of Metyrosine

Disease Entry	ICD 11	Status	REF
Pheochromocytoma	5A75	Approved	[4]

Metyrosine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tyrosine 3-monooxygenase (TH)	TTUHP71	TY3H_HUMAN	Binder	[46]

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