Details of the Drug Combination

General Information of Drug Combination (ID: DC7RRB2)

• Drug Combination Name: Dacarbazine + Mercaptopurine
• Indication: Anaplastic large cell lymphoma; Status: Investigative [1]
• Component Drugs:
  Dacarbazine (DMNPZL4): Small molecular drug
  Mercaptopurine (DMTM2IK): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SR
  Zero Interaction Potency (ZIP) Score: 2.27
  Bliss Independence Score: 1.53
  Loewe Additivity Score: 0.78
  LHighest Single Agent (HSA) Score: 4.35

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Dacarbazine

Disease Entry	ICD 11	Status	REF
Adenocarcinoma	2D40	Approved	[2]
Astrocytoma	2A00.0Y	Approved	[2]
Brain disease	8C70-8E61	Approved	[2]
Central nervous system disease	8A04-8D87	Approved	[2]
Glioblastoma	2A00	Approved	[2]
Gliosarcoma	N.A.	Approved	[2]
Melanoma	2C30	Approved	[3]
Classic Hodgkin lymphoma	N.A.	Investigative	[2]
Neuroblastoma	2D11.2	Investigative	[2]

Dacarbazine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Breaker	[9]

Dacarbazine Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[10]
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Metabolism	[11]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[12]

Dacarbazine Interacts with 12 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Increases Expression	[13]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[8]
Interferon regulatory factor 1 (IRF1)	OT43DI6J	IRF1_HUMAN	Increases Expression	[14]
Methylated-DNA--protein-cysteine methyltransferase (MGMT)	OT40A9WH	MGMT_HUMAN	Decreases Activity	[15]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Response To Substance	[16]
DNA repair nuclease/redox regulator APEX1 (APEX1)	OT53OI14	APEX1_HUMAN	Increases Response To Substance	[17]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)	OTA675TJ	GTR1_HUMAN	Decreases Response To Substance	[18]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Response To Substance	[19]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Response To Substance	[19]
Clusterin (CLU)	OTQGG0JM	CLUS_HUMAN	Affects Response To Substance	[20]
Mitogen-activated protein kinase kinase kinase 1 (MAP3K1)	OTS3FVTY	M3K1_HUMAN	Decreases Response To Substance	[19]
Erythropoietin (EPO)	OTZ90CN4	EPO_HUMAN	Decreases Response To Substance	[21]

Indication(s) of Mercaptopurine

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

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	[7]
Inosine-5'-monophosphate dehydrogenase 1 (IMPDH1)	TTL7C8Q	IMDH1_HUMAN	Inhibitor	[24]
SARS-CoV papain-like proteinase (PL-PRO)	TTRGHB2	R1AB_CVHSA (819-2740)	Inhibitor	[7]
Amidophosphoribosyltransferase (PPAT)	TTZFTY4	PUR1_HUMAN	Breaker	[25]

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	[26]
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[27]
Multidrug resistance-associated protein 5 (ABCC5)	DTYVM24	MRP5_HUMAN	Substrate	[28]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[29]
Concentrative nucleoside transporter 2 (SLC28A2)	DT82KPY	S28A2_HUMAN	Substrate	[30]
Concentrative Na(+)-nucleoside cotransporter 3 (SLC28A3)	DT4YL5R	S28A3_HUMAN	Substrate	[31]
Equilibrative nucleoside transporter 1 (SLC29A1)	DTXD1TQ	S29A1_HUMAN	Substrate	[30]
Equilibrative nucleoside transporter 2 (SLC29A2)	DTW78DQ	S29A2_HUMAN	Substrate	[30]
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	[36]
Thiopurine S-methyltransferase (TPMT)	OTFOX70W	TPMT_HUMAN	Decreases Metabolism	[37]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[38]
Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2)	OTPG0K7E	IMDH2_HUMAN	Increases Expression	[38]
Glutathione peroxidase 2 (GPX2)	OTXI2NTI	GPX2_HUMAN	Increases Expression	[38]
Glutathione peroxidase 3 (GPX3)	OT6PK94R	GPX3_HUMAN	Increases Expression	[38]
Glutamate--cysteine ligase regulatory subunit (GCLM)	OT6CP234	GSH0_HUMAN	Increases Expression	[38]
Glutathione synthetase (GSS)	OTVSBEIW	GSHB_HUMAN	Increases Expression	[38]
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)	OTBPMIMW	G3P_HUMAN	Affects Localization	[39]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Affects Activity	[40]
Dual specificity mitogen-activated protein kinase kinase 1 (MAP2K1)	OT4Y9NQI	MP2K1_HUMAN	Decreases Phosphorylation	[22]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Affects Localization	[22]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[22]
Molybdenum cofactor sulfurase (MOCOS)	OT0TL3Q5	MOCOS_HUMAN	Decreases Oxidation	[41]
HLA class II histocompatibility antigen, DQ alpha 1 chain (HLA-DQA1)	OTC6GISG	DQA1_HUMAN	Affects Response To Substance	[42]
Major vault protein (MVP)	OTJGHJRB	MVP_HUMAN	Decreases Response To Substance	[43]
HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1)	OTRGGIFP	DRB1_HUMAN	Affects Response To Substance	[42]
Glutathione S-transferase Mu 1 (GSTM1)	OTSBF2MO	GSTM1_HUMAN	Affects Response To Substance	[23]
Nucleotide triphosphate diphosphatase NUDT15 (NUDT15)	OTX8SZOT	NUD15_HUMAN	Increases Response To Substance	[44]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Large cell lung carcinoma	DCZN6XX	NCI-H460	Investigative	[1]
Malignant melanoma	DCDWL27	LOX IMVI	Investigative	[1]
Mixed endometrioid and clear cell carcinoma	DCJPO9R	IGROV1	Investigative	[1]

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