Details of the Drug Combination

General Information of Drug Combination (ID: DCMTSJQ)

• Drug Combination Name: Hydralazine + Tacrolimus
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Hydralazine (DMU8JGH): Small molecular drug
  Tacrolimus (DMZ7XNQ): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 31.27
  Bliss Independence Score: 31.27
  Loewe Additivity Score: 40.15
  LHighest Single Agent (HSA) Score: 40.17

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Hydralazine

Disease Entry	ICD 11	Status	REF
Chronic heart failure	BD1Z	Approved	[2]
Hypertension	BA00-BA04	Approved	[3]
Malignant essential hypertension	BA00	Approved	[2]

Hydralazine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Membrane copper amine oxidase (AOC3)	TT7HC21	AOC3_HUMAN	Modulator	[6]

Hydralazine Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
RNA cytidine acetyltransferase (hALP)	DEZV4AP	NAT10_HUMAN	Metabolism	[7]
N-acetyltransferase 1 (NAT1)	DE7OAB3	ARY1_HUMAN	Metabolism	[8]
N-acetyltransferase 2 (NAT2)	DER7TA0	ARY2_HUMAN	Metabolism	[8]

Hydralazine Interacts with 9 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Arylamine N-acetyltransferase 2 (NAT2)	OTBPDQOY	ARY2_HUMAN	Increases Acetylation	[9]
Methylated-DNA--protein-cysteine methyltransferase (MGMT)	OT40A9WH	MGMT_HUMAN	Increases Expression	[10]
Adenomatous polyposis coli protein (APC)	OTKV0TIK	APC_HUMAN	Decreases Methylation	[10]
Cyclin-dependent kinase inhibitor 2A (CDKN2A)	OTN0ZWAE	CDN2A_HUMAN	Decreases Methylation	[10]
Bis(5'-adenosyl)-triphosphatase (FHIT)	OTGWBSLA	FHIT_HUMAN	Increases Expression	[10]
Death-associated protein kinase 1 (DAPK1)	OTNCNUCO	DAPK1_HUMAN	Increases Expression	[10]
Renin (REN)	OT52GZR2	RENI_HUMAN	Increases Activity	[11]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Decreases Expression	[12]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[13]

Indication(s) of Tacrolimus

Disease Entry	ICD 11	Status	REF
Graft-versus-host disease	4B24	Approved	[4]
Hepatosplenic T-cell lymphoma	N.A.	Approved	[4]
Kidney transplant rejection	NE84	Approved	[4]
Large granular lymphocytic leukemia	2A90.1	Approved	[4]
Leukemia	N.A.	Approved	[4]
Lupus nephritis	4A40.0Y	Approved	[4]
MALT lymphoma	N.A.	Approved	[4]
Myeloproliferative neoplasm	2A20	Approved	[4]
Nodal marginal zone lymphoma	2A85.0	Approved	[4]
Organ transplant rejection	NE84	Approved	[5]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	N.A.	Approved	[4]
Recurrent adult burkitt lymphoma	2A85.6	Approved	[4]
Small intestine lymphoma	N.A.	Approved	[4]
Splenic marginal zone lymphoma	N.A.	Approved	[4]
Testicular lymphoma	N.A.	Approved	[4]
Ocular allergy	4A81	Phase 3	[5]
Classic Hodgkin lymphoma	N.A.	Investigative	[4]

Tacrolimus Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Calcineurin (PPP3CA)	TTA4LDE	PP2BA_HUMAN	Inhibitor	[16]

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	[17]

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	[18]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[19]
NADPH-cytochrome P450 reductase (CPR)	DE3N2FM	NCPR_HUMAN	Metabolism	[20]
Ribosomal 23S RNA methyltransferase Erm (erm)	DEW6V07	A0A5N1AHF6_CORAY	Metabolism	[21]
Ribosomal 23S RNA methyltransferase Erm (erm)	DEA65D8	A0A381KDL2_CORJE	Metabolism	[21]

Tacrolimus Interacts with 23 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Response To Substance	[22]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Increases Expression	[23]
Cytochrome b-245 light chain (CYBA)	OT16N9ZO	CY24A_HUMAN	Increases Expression	[23]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[24]
Natural cytotoxicity triggering receptor 3 (NCR3)	OT20M764	NCTR3_HUMAN	Increases Expression	[25]
Hepatocyte growth factor-regulated tyrosine kinase substrate (HGS)	OTCYYCAC	HGS_HUMAN	Increases Expression	[15]
Rho guanine nucleotide exchange factor 11 (ARHGEF11)	OTDOMEH6	ARHGB_HUMAN	Increases Expression	[15]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[26]
Actin-related protein 2/3 complex subunit 5 (ARPC5)	OTFNMMDL	ARPC5_HUMAN	Increases Expression	[15]
G2/mitotic-specific cyclin-B2 (CCNB2)	OTIEXTDK	CCNB2_HUMAN	Decreases Expression	[26]
Zinc finger protein SNAI1 (SNAI1)	OTDPYAMC	SNAI1_HUMAN	Increases Expression	[14]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Increases Expression	[27]
Interleukin-3 (IL3)	OT0CQ35N	IL3_HUMAN	Decreases Expression	[28]
Cadherin-1 (CDH1)	OTFJMXPM	CADH1_HUMAN	Decreases Expression	[14]
C-C motif chemokine 5 (CCL5)	OTSCA5CK	CCL5_HUMAN	Decreases Expression	[29]
Ras-related protein Rab-4A (RAB4A)	OT7BL9WW	RAB4A_HUMAN	Increases Expression	[15]
T-lymphocyte activation antigen CD80 (CD80)	OTJBLUQE	CD80_HUMAN	Decreases Expression	[30]
Troponin T, cardiac muscle (TNNT2)	OT80NN7R	TNNT2_HUMAN	Increases Expression	[31]
Tumor necrosis factor ligand superfamily member 6 (FASLG)	OTZARCHH	TNFL6_HUMAN	Decreases Secretion	[32]
Eotaxin (CCL11)	OT3BIFPK	CCL11_HUMAN	Decreases Expression	[29]
Lethal(2) giant larvae protein homolog 1 (LLGL1)	OTAIQSXZ	L2GL1_HUMAN	Increases Expression	[15]
Calcineurin subunit B type 1 (PPP3R1)	OTGQNFJQ	CANB1_HUMAN	Increases ADR	[33]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Response To Substance	[34]

References

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• [2] Hydralazine FDA Label
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• [4] Tacrolimus FDA Label
• [5] 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: 6784).
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