Details of the Drug Combination

General Information of Drug Combination (ID: DCZAX1F)

• Drug Combination Name: Tacrolimus + Epinephrine
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Tacrolimus (DMZ7XNQ): Small molecular drug
  Epinephrine (DM3KJBC): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 8.12
  Bliss Independence Score: 8.12
  Loewe Additivity Score: 9.21
  LHighest Single Agent (HSA) Score: 9.27

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Tacrolimus

Disease Entry	ICD 11	Status	REF
Graft-versus-host disease	4B24	Approved	[2]
Hepatosplenic T-cell lymphoma	N.A.	Approved	[2]
Kidney transplant rejection	NE84	Approved	[2]
Large granular lymphocytic leukemia	2A90.1	Approved	[2]
Leukemia	N.A.	Approved	[2]
Lupus nephritis	4A40.0Y	Approved	[2]
MALT lymphoma	N.A.	Approved	[2]
Myeloproliferative neoplasm	2A20	Approved	[2]
Nodal marginal zone lymphoma	2A85.0	Approved	[2]
Organ transplant rejection	NE84	Approved	[3]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	N.A.	Approved	[2]
Recurrent adult burkitt lymphoma	2A85.6	Approved	[2]
Small intestine lymphoma	N.A.	Approved	[2]
Splenic marginal zone lymphoma	N.A.	Approved	[2]
Testicular lymphoma	N.A.	Approved	[2]
Ocular allergy	4A81	Phase 3	[3]
Classic Hodgkin lymphoma	N.A.	Investigative	[2]

Tacrolimus Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Calcineurin (PPP3CA)	TTA4LDE	PP2BA_HUMAN	Inhibitor	[8]

Tacrolimus Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[9]

Tacrolimus Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[10]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[11]
NADPH-cytochrome P450 reductase (CPR)	DE3N2FM	NCPR_HUMAN	Metabolism	[12]
Ribosomal 23S RNA methyltransferase Erm (erm)	DEW6V07	A0A5N1AHF6_CORAY	Metabolism	[13]
Ribosomal 23S RNA methyltransferase Erm (erm)	DEA65D8	A0A381KDL2_CORJE	Metabolism	[13]

Tacrolimus Interacts with 49 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Decreases Methylation	[14]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Decreases Methylation	[14]
NADPH--cytochrome P450 reductase (POR)	OTVIDOCH	NCPR_HUMAN	Affects Response To Substance	[15]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Response To Substance	[16]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Increases Expression	[17]
Cytochrome b-245 light chain (CYBA)	OT16N9ZO	CY24A_HUMAN	Increases Expression	[17]
Nitric oxide synthase 3 (NOS3)	OTLDT7NR	NOS3_HUMAN	Increases Expression	[17]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[18]
Natural cytotoxicity triggering receptor 3 (NCR3)	OT20M764	NCTR3_HUMAN	Increases Expression	[19]
Hepatocyte growth factor-regulated tyrosine kinase substrate (HGS)	OTCYYCAC	HGS_HUMAN	Increases Expression	[7]
Rho guanine nucleotide exchange factor 11 (ARHGEF11)	OTDOMEH6	ARHGB_HUMAN	Increases Expression	[7]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[20]
Actin-related protein 2/3 complex subunit 5 (ARPC5)	OTFNMMDL	ARPC5_HUMAN	Increases Expression	[7]
G2/mitotic-specific cyclin-B2 (CCNB2)	OTIEXTDK	CCNB2_HUMAN	Decreases Expression	[20]
Zinc finger protein SNAI1 (SNAI1)	OTDPYAMC	SNAI1_HUMAN	Increases Expression	[6]
Insulin (INS)	OTZ85PDU	INS_HUMAN	Decreases Expression	[21]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Secretion	[22]
Interferon gamma (IFNG)	OTXG9JM7	IFNG_HUMAN	Decreases Expression	[23]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Expression	[24]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Increases Expression	[25]
Fibronectin (FN1)	OTB5ZN4Q	FINC_HUMAN	Increases Expression	[25]
Granulocyte-macrophage colony-stimulating factor (CSF2)	OT1M7D28	CSF2_HUMAN	Decreases Expression	[23]
Interleukin-4 (IL4)	OTOXBWAU	IL4_HUMAN	Decreases Expression	[23]
Interleukin-5 (IL5)	OTAFPSCO	IL5_HUMAN	Decreases Expression	[26]
Interleukin-3 (IL3)	OT0CQ35N	IL3_HUMAN	Decreases Expression	[23]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[27]
Cadherin-1 (CDH1)	OTFJMXPM	CADH1_HUMAN	Decreases Expression	[6]
C-C motif chemokine 5 (CCL5)	OTSCA5CK	CCL5_HUMAN	Decreases Expression	[26]
Ras-related protein Rab-4A (RAB4A)	OT7BL9WW	RAB4A_HUMAN	Increases Expression	[7]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Decreases Degradation	[22]
T-lymphocyte activation antigen CD80 (CD80)	OTJBLUQE	CD80_HUMAN	Decreases Expression	[28]
T-lymphocyte activation antigen CD86 (CD86)	OTJCSBPC	CD86_HUMAN	Decreases Expression	[28]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Cleavage	[29]
Troponin T, cardiac muscle (TNNT2)	OT80NN7R	TNNT2_HUMAN	Increases Expression	[30]
Tumor necrosis factor ligand superfamily member 6 (FASLG)	OTZARCHH	TNFL6_HUMAN	Decreases Secretion	[31]
Glycogen synthase kinase-3 alpha (GSK3A)	OT0F6DWV	GSK3A_HUMAN	Increases Phosphorylation	[6]
Glycogen synthase kinase-3 beta (GSK3B)	OTL3L14B	GSK3B_HUMAN	Increases Phosphorylation	[6]
Eotaxin (CCL11)	OT3BIFPK	CCL11_HUMAN	Decreases Expression	[26]
C-C chemokine receptor type 3 (CCR3)	OT6GBUFA	CCR3_HUMAN	Decreases Expression	[26]
LIM domain kinase 1 (LIMK1)	OTFZ8MZ0	LIMK1_HUMAN	Increases Expression	[7]
Interleukin-2 (IL2)	OTGI4NSA	IL2_HUMAN	Decreases Expression	[23]
Neutrophil gelatinase-associated lipocalin (LCN2)	OTSB42BR	NGAL_HUMAN	Increases Expression	[25]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[29]
Lethal(2) giant larvae protein homolog 1 (LLGL1)	OTAIQSXZ	L2GL1_HUMAN	Increases Expression	[7]
Calcineurin subunit B type 1 (PPP3R1)	OTGQNFJQ	CANB1_HUMAN	Increases ADR	[32]
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Decreases Response To Substance	[33]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Response To Substance	[33]
Peroxisome proliferator-activated receptor alpha (PPARA)	OTK095PP	PPARA_HUMAN	Affects Response To Substance	[15]
Cytochrome P450 3A7 (CYP3A7)	OTTCDHHM	CP3A7_HUMAN	Decreases Methylation	[14]

Indication(s) of Epinephrine

Disease Entry	ICD 11	Status	REF
Acute asthma	CA23	Approved	[4]
Allergy	4A80-4A85	Approved	[5]
Anaphylaxis	N.A.	Approved	[4]
Bronchiectasis	CA24	Approved	[4]
Bronchitis	CA20	Approved	[4]
Periodontitis	DA0C	Approved	[4]
Pulmonary emphysema	CA21.Z	Approved	[4]
Severe asthma	CA23	Approved	[4]
Asthma	CA23	Investigative	[4]

Epinephrine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adrenergic receptor beta-1 (ADRB1)	TTR6W5O	ADRB1_HUMAN	Agonist	[34]

Epinephrine Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic cation transporter 3 (SLC22A3)	DT6201N	S22A3_HUMAN	Substrate	[35]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[36]

Epinephrine Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[37]
Sulfotransferase 1A1 (SULT1A1)	DEYWLRK	ST1A1_HUMAN	Metabolism	[38]
Thiopurine methyltransferase (TPMT)	DEFQ8VO	TPMT_HUMAN	Metabolism	[39]
Catechol O-methyltransferase (COMT)	DEV3T4A	COMT_HUMAN	Metabolism	[40]
Monoamine oxidase type A (MAO-A)	DERE4TU	AOFA_HUMAN	Metabolism	[41]

Epinephrine Interacts with 33 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Catechol O-methyltransferase (COMT)	OTPWKTQG	COMT_HUMAN	Increases Methylation	[42]
Solute carrier family 22 member 3 (SLC22A3)	OTQYGVXX	S22A3_HUMAN	Increases Uptake	[43]
Superoxide dismutase (SOD1)	OT39TA1L	SODC_HUMAN	Increases Expression	[44]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[44]
Carbonic anhydrase 2 (CA2)	OTJRMUAG	CAH2_HUMAN	Increases Expression	[45]
Integrin alpha-V (ITGAV)	OTAM7JTR	ITAV_HUMAN	Increases Expression	[45]
Cathepsin K (CTSK)	OTT3YX5O	CATK_HUMAN	Increases Expression	[45]
Renin (REN)	OT52GZR2	RENI_HUMAN	Increases Activity	[46]
Insulin (INS)	OTZ85PDU	INS_HUMAN	Decreases Expression	[47]
Beta-2 adrenergic receptor (ADRB2)	OTSDOX4Q	ADRB2_HUMAN	Increases Activity	[48]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Decreases Cleavage	[49]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Increases Expression	[49]
Proliferating cell nuclear antigen (PCNA)	OTHZ1RIA	PCNA_HUMAN	Increases Expression	[49]
Pyruvate kinase PKM (PKM)	OTLHHMC2	KPYM_HUMAN	Increases Expression	[49]
Alpha-1D adrenergic receptor (ADRA1D)	OTW2CD1O	ADA1D_HUMAN	Increases Activity	[50]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[51]
Alpha-1A adrenergic receptor (ADRA1A)	OTUIWCL5	ADA1A_HUMAN	Increases Activity	[50]
Alpha-1B adrenergic receptor (ADRA1B)	OTSAYAFD	ADA1B_HUMAN	Increases Activity	[50]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[51]
Tumor necrosis factor ligand superfamily member 6 (FASLG)	OTZARCHH	TNFL6_HUMAN	Increases Expression	[51]
Hexokinase-2 (HK2)	OTC0GCQO	HXK2_HUMAN	Increases Expression	[49]
Ephrin type-A receptor 4 (EPHA4)	OT3AMK0C	EPHA4_HUMAN	Increases Phosphorylation	[52]
Hormone-sensitive lipase (LIPE)	OTMMVJ8A	LIPS_HUMAN	Increases Activity	[53]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Expression	[49]
P2X purinoceptor 7 (P2RX7)	OTNJ9XPL	P2RX7_HUMAN	Decreases Activity	[54]
Leptin (LEP)	OT5Q7ODW	LEP_HUMAN	Increases ADR	[32]
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Decreases Response To Substance	[55]
Sulfotransferase 1A3 (SULT1A4)	OTHJ8WWV	ST1A3_HUMAN	Increases Sulfation	[56]
Glutathione reductase, mitochondrial (GSR)	OTM2TUYM	GSHR_HUMAN	Increases ADR	[32]
Neuron-specific vesicular protein calcyon (CALY)	OTQ7EMPU	CALY_HUMAN	Decreases Secretion	[57]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases ADR	[32]
Equilibrative nucleoside transporter 4 (SLC29A4)	OTWTZXMX	S29A4_HUMAN	Increases Uptake	[43]
Alpha-2A adrenergic receptor (ADRA2A)	OTZFGOTP	ADA2A_HUMAN	Increases ADR	[32]

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