Details of the Drug Combination

General Information of Drug Combination (ID: DCFC1UL)

• Drug Combination Name: Digitoxin + Mercaptopurine
• Indication: High grade ovarian serous adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Digitoxin (DMWVIGP): Small molecular drug
  Mercaptopurine (DMTM2IK): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: NCI\\/ADR-RES
  Zero Interaction Potency (ZIP) Score: 3.23
  Bliss Independence Score: 4.31
  Loewe Additivity Score: 1.05
  LHighest Single Agent (HSA) Score: 7

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Digitoxin

Disease Entry	ICD 11	Status	REF
Arrhythmia	BC9Z	Approved	[2]
Congestive cardiac insufficiency	BD1Z	Approved	[2]
Heart failure	BD10-BD13	Approved	[2]

Digitoxin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Sodium/potassium-transporting ATPase (SPT ATPase)	TTQ38E9	AT1A1_HUMAN; AT1A2_HUMAN; AT1A3_HUMAN; AT1B1_HUMAN; AT1B2_HUMAN; AT1B3_HUMAN	Inhibitor	[7]

Digitoxin Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[8]

Digitoxin Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[10]
Sulfotransferase 1A1 (SULT1A1)	DEYWLRK	ST1A1_HUMAN	Metabolism	[11]

Digitoxin Interacts with 22 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Transport	[12]
Nitric oxide synthase 3 (NOS3)	OTLDT7NR	NOS3_HUMAN	Increases Activity	[13]
Serine/threonine-protein kinase Chk1 (CHEK1)	OTTTI622	CHK1_HUMAN	Decreases Expression	[14]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[14]
Serine/threonine-protein kinase Chk2 (CHEK2)	OT8ZPCNS	CHK2_HUMAN	Decreases Expression	[14]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Decreases Expression	[14]
Cyclin-dependent kinase 1 (CDK1)	OTW1SC2N	CDK1_HUMAN	Decreases Expression	[14]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Secretion	[15]
G2/mitotic-specific cyclin-B1 (CCNB1)	OT19S7E5	CCNB1_HUMAN	Decreases Expression	[14]
Ribosomal protein S6 kinase beta-1 (RPS6KB1)	OTAELNGX	KS6B1_HUMAN	Decreases Phosphorylation	[16]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[16]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Decreases Phosphorylation	[15]
Tyrosine-protein phosphatase non-receptor type 6 (PTPN6)	OT33XNZM	PTN6_HUMAN	Increases Expression	[16]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Decreases Expression	[14]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Decreases Expression	[14]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Decreases Expression	[14]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Cleavage	[14]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN)	OTOWDUNT	PTEN_HUMAN	Increases Expression	[16]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Increases Expression	[14]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1)	OTHBQVD5	4EBP1_HUMAN	Decreases Phosphorylation	[16]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Cleavage	[14]
E3 SUMO-protein ligase PIAS3 (PIAS3)	OT3TWH9R	PIAS3_HUMAN	Increases Expression	[16]

Indication(s) of Mercaptopurine

Disease Entry	ICD 11	Status	REF
Acute lymphoblastic leukaemia	2A85	Approved	[3]
Acute lymphocytic leukaemia	2B33.3	Approved	[4]
Crohn disease	DD70	Phase 4	[5]
Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[6]
Severe acute respiratory syndrome (SARS)	1D65	Preclinical	[6]

Mercaptopurine Interacts with 4 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
MERS-CoV papain-like proteinase (PL-PRO)	TTYJOLE	R1AB_CVEMC (854-2740)	Inhibitor	[6]
Inosine-5'-monophosphate dehydrogenase 1 (IMPDH1)	TTL7C8Q	IMDH1_HUMAN	Inhibitor	[19]
SARS-CoV papain-like proteinase (PL-PRO)	TTRGHB2	R1AB_CVHSA (819-2740)	Inhibitor	[6]
Amidophosphoribosyltransferase (PPAT)	TTZFTY4	PUR1_HUMAN	Breaker	[20]

Mercaptopurine Interacts with 9 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[21]
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[22]
Multidrug resistance-associated protein 5 (ABCC5)	DTYVM24	MRP5_HUMAN	Substrate	[23]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[24]
Concentrative nucleoside transporter 2 (SLC28A2)	DT82KPY	S28A2_HUMAN	Substrate	[25]
Concentrative Na(+)-nucleoside cotransporter 3 (SLC28A3)	DT4YL5R	S28A3_HUMAN	Substrate	[26]
Equilibrative nucleoside transporter 1 (SLC29A1)	DTXD1TQ	S29A1_HUMAN	Substrate	[25]
Equilibrative nucleoside transporter 2 (SLC29A2)	DTW78DQ	S29A2_HUMAN	Substrate	[25]
Equilibrative nucleobase transporter 1 (SLC43A3)	DTGBPR5	S43A3_HUMAN	Substrate	[27]

Mercaptopurine Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[28]
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Metabolism	[28]
Thiopurine methyltransferase (TPMT)	DEFQ8VO	TPMT_HUMAN	Metabolism	[29]

Mercaptopurine Interacts with 20 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Thiopurine S-methyltransferase (TPMT)	OTFOX70W	TPMT_HUMAN	Affects Response To Substance	[30]
Nuclear receptor subfamily 4 group A member 3 (NR4A3)	OTPBE9R1	NR4A3_HUMAN	Increases ADR	[31]
Thiopurine S-methyltransferase (TPMT)	OTFOX70W	TPMT_HUMAN	Decreases Metabolism	[32]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[33]
Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2)	OTPG0K7E	IMDH2_HUMAN	Increases Expression	[33]
Glutathione peroxidase 2 (GPX2)	OTXI2NTI	GPX2_HUMAN	Increases Expression	[33]
Glutathione peroxidase 3 (GPX3)	OT6PK94R	GPX3_HUMAN	Increases Expression	[33]
Glutamate--cysteine ligase regulatory subunit (GCLM)	OT6CP234	GSH0_HUMAN	Increases Expression	[33]
Glutathione synthetase (GSS)	OTVSBEIW	GSHB_HUMAN	Increases Expression	[33]
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)	OTBPMIMW	G3P_HUMAN	Affects Localization	[34]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Affects Activity	[35]
Dual specificity mitogen-activated protein kinase kinase 1 (MAP2K1)	OT4Y9NQI	MP2K1_HUMAN	Decreases Phosphorylation	[17]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Affects Localization	[17]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[17]
Molybdenum cofactor sulfurase (MOCOS)	OT0TL3Q5	MOCOS_HUMAN	Decreases Oxidation	[36]
HLA class II histocompatibility antigen, DQ alpha 1 chain (HLA-DQA1)	OTC6GISG	DQA1_HUMAN	Affects Response To Substance	[37]
Major vault protein (MVP)	OTJGHJRB	MVP_HUMAN	Decreases Response To Substance	[38]
HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1)	OTRGGIFP	DRB1_HUMAN	Affects Response To Substance	[37]
Glutathione S-transferase Mu 1 (GSTM1)	OTSBF2MO	GSTM1_HUMAN	Affects Response To Substance	[18]
Nucleotide triphosphate diphosphatase NUDT15 (NUDT15)	OTX8SZOT	NUD15_HUMAN	Increases Response To Substance	[39]

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