Details of the Drug Combination

General Information of Drug Combination (ID: DC7CYMZ)

• Drug Combination Name: Thioguanine + Mercaptopurine
• Indication: Adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Thioguanine (DM7NKEV): Small molecular drug
  Mercaptopurine (DMTM2IK): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: NCIH23
  Zero Interaction Potency (ZIP) Score: 1.93
  Bliss Independence Score: 3.93
  Loewe Additivity Score: 4.15
  LHighest Single Agent (HSA) Score: 6.16

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Thioguanine

Disease Entry	ICD 11	Status	REF
Acute lymphocytic leukaemia	2B33.3	Approved	[2]
Acute myelogenous leukaemia	2A41	Approved	[3]
Acute myeloid leukaemia	2A60	Approved	[4]
Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[5]
Severe acute respiratory syndrome (SARS)	1D65	Preclinical	[5]

Thioguanine Interacts with 3 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	[5]
Inosine-5'-monophosphate dehydrogenase (IMPDH)	TTCAQMW	NOUNIPROTAC	Intercalator	[8]
SARS-CoV papain-like proteinase (PL-PRO)	TTRGHB2	R1AB_CVHSA (819-2740)	Inhibitor	[5]

Thioguanine Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[9]
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[10]
Concentrative Na(+)-nucleoside cotransporter 3 (SLC28A3)	DT4YL5R	S28A3_HUMAN	Substrate	[11]

Thioguanine Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Thiopurine methyltransferase (TPMT)	DEFQ8VO	TPMT_HUMAN	Metabolism	[12]
Hypoxanthine phosphoribosyltransferase (HPRT1)	DEVXTP5	HPRT_HUMAN	Metabolism	[13]

Thioguanine Interacts with 11 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Thiopurine S-methyltransferase (TPMT)	OTFOX70W	TPMT_HUMAN	Increases ADR	[14]
Hypoxanthine-guanine phosphoribosyltransferase (HPRT1)	OTOEEEXG	HPRT_HUMAN	Decreases Response To Substance	[15]
Thiopurine S-methyltransferase (TPMT)	OTFOX70W	TPMT_HUMAN	Increases ADR	[16]
Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2)	OTPG0K7E	IMDH2_HUMAN	Increases Expression	[17]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Activity	[18]
Dystrophin (DMD)	OTD21T5J	DMD_HUMAN	Increases Splicing	[19]
Occludin (OCLN)	OTSUTVWL	OCLN_HUMAN	Decreases Activity	[20]
DNA mismatch repair protein Msh2 (MSH2)	OT10H1AB	MSH2_HUMAN	Increases Response To Substance	[21]
ATP-binding cassette sub-family C member 5 (ABCC5)	OT34G4US	MRP5_HUMAN	Decreases Response To Substance	[22]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Response To Substance	[18]
Baculoviral IAP repeat-containing protein 2 (BIRC2)	OTFXFREP	BIRC2_HUMAN	Decreases Response To Substance	[23]

Indication(s) of Mercaptopurine

Disease Entry	ICD 11	Status	REF
Acute lymphoblastic leukaemia	2A85	Approved	[6]
Acute lymphocytic leukaemia	2B33.3	Approved	[2]
Crohn disease	DD70	Phase 4	[7]
Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[5]
Severe acute respiratory syndrome (SARS)	1D65	Preclinical	[5]

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	[5]
Inosine-5'-monophosphate dehydrogenase 1 (IMPDH1)	TTL7C8Q	IMDH1_HUMAN	Inhibitor	[26]
SARS-CoV papain-like proteinase (PL-PRO)	TTRGHB2	R1AB_CVHSA (819-2740)	Inhibitor	[5]
Amidophosphoribosyltransferase (PPAT)	TTZFTY4	PUR1_HUMAN	Breaker	[27]

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	[9]
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[28]
Multidrug resistance-associated protein 5 (ABCC5)	DTYVM24	MRP5_HUMAN	Substrate	[29]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[30]
Concentrative nucleoside transporter 2 (SLC28A2)	DT82KPY	S28A2_HUMAN	Substrate	[31]
Concentrative Na(+)-nucleoside cotransporter 3 (SLC28A3)	DT4YL5R	S28A3_HUMAN	Substrate	[11]
Equilibrative nucleoside transporter 1 (SLC29A1)	DTXD1TQ	S29A1_HUMAN	Substrate	[31]
Equilibrative nucleoside transporter 2 (SLC29A2)	DTW78DQ	S29A2_HUMAN	Substrate	[31]
Equilibrative nucleobase transporter 1 (SLC43A3)	DTGBPR5	S43A3_HUMAN	Substrate	[32]

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	[33]
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Metabolism	[33]
Thiopurine methyltransferase (TPMT)	DEFQ8VO	TPMT_HUMAN	Metabolism	[34]

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	[35]
Nuclear receptor subfamily 4 group A member 3 (NR4A3)	OTPBE9R1	NR4A3_HUMAN	Increases ADR	[14]
Thiopurine S-methyltransferase (TPMT)	OTFOX70W	TPMT_HUMAN	Decreases Metabolism	[36]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[17]
Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2)	OTPG0K7E	IMDH2_HUMAN	Increases Expression	[17]
Glutathione peroxidase 2 (GPX2)	OTXI2NTI	GPX2_HUMAN	Increases Expression	[17]
Glutathione peroxidase 3 (GPX3)	OT6PK94R	GPX3_HUMAN	Increases Expression	[17]
Glutamate--cysteine ligase regulatory subunit (GCLM)	OT6CP234	GSH0_HUMAN	Increases Expression	[17]
Glutathione synthetase (GSS)	OTVSBEIW	GSHB_HUMAN	Increases Expression	[17]
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)	OTBPMIMW	G3P_HUMAN	Affects Localization	[37]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Affects Activity	[38]
Dual specificity mitogen-activated protein kinase kinase 1 (MAP2K1)	OT4Y9NQI	MP2K1_HUMAN	Decreases Phosphorylation	[24]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Affects Localization	[24]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[24]
Molybdenum cofactor sulfurase (MOCOS)	OT0TL3Q5	MOCOS_HUMAN	Decreases Oxidation	[39]
HLA class II histocompatibility antigen, DQ alpha 1 chain (HLA-DQA1)	OTC6GISG	DQA1_HUMAN	Affects Response To Substance	[40]
Major vault protein (MVP)	OTJGHJRB	MVP_HUMAN	Decreases Response To Substance	[41]
HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1)	OTRGGIFP	DRB1_HUMAN	Affects Response To Substance	[40]
Glutathione S-transferase Mu 1 (GSTM1)	OTSBF2MO	GSTM1_HUMAN	Affects Response To Substance	[25]
Nucleotide triphosphate diphosphatase NUDT15 (NUDT15)	OTX8SZOT	NUD15_HUMAN	Increases Response To Substance	[42]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Anaplastic large cell lymphoma	DC5VWHV	SR	Investigative	[43]
Mixed endometrioid and clear cell carcinoma	DCE81J7	IGROV1	Investigative	[1]

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