Details of the Drug Combination

General Information of Drug Combination (ID: DCHB204)

• Drug Combination Name: Thioguanine + Plicamycin
• Indication: Anaplastic large cell lymphoma; Status: Investigative [1]
• Component Drugs:
  Thioguanine (DM7NKEV): Small molecular drug
  Plicamycin (DM7C8YV): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SR
  Zero Interaction Potency (ZIP) Score: 12.99
  Bliss Independence Score: 13.03
  Loewe Additivity Score: 9.82
  LHighest Single Agent (HSA) Score: 14.33

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 Plicamycin

Disease Entry	ICD 11	Status	REF
Hypercalcaemia	5B91.0	Approved	[2]
Testicular cancer	2C80	Approved	[2]
Solid tumour/cancer	2A00-2F9Z	Withdrawn from market	[6]
Lung cancer	2C25.0	Investigative	[7]
Ovarian cancer	2C73	Investigative	[7]

Plicamycin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
RNA synthesis (hRNA synth)	TTX2AYW	NOUNIPROTAC	Modulator	[25]

Plicamycin Interacts with 16 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2)	OT3K7HY5	DHB2_HUMAN	Decreases Expression	[26]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Expression	[27]
Aryl hydrocarbon receptor (AHR)	OTFE4EYE	AHR_HUMAN	Decreases Expression	[27]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Expression	[27]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[28]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Activity	[28]
Epoxide hydrolase 1 (EPHX1)	OTBKWQER	HYEP_HUMAN	Decreases Expression	[29]
Transcription factor Sp1 (SP1)	OTISPT4X	SP1_HUMAN	Decreases Expression	[24]
Proto-oncogene tyrosine-protein kinase Src (SRC)	OTETYX40	SRC_HUMAN	Decreases Expression	[30]
Tissue factor (F3)	OT3MSU3B	TF_HUMAN	Decreases Expression	[31]
Tyrosine-protein kinase receptor UFO (AXL)	OTKA2SUX	UFO_HUMAN	Decreases Expression	[32]
Transcription factor Sp3 (SP3)	OTYDQZ1T	SP3_HUMAN	Decreases Expression	[24]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Expression	[33]
Epidermal growth factor receptor kinase substrate 8 (EPS8)	OTZ6ES6V	EPS8_HUMAN	Decreases Expression	[30]
TNFAIP3-interacting protein 1 (TNIP1)	OTRAOTEW	TNIP1_HUMAN	Decreases Expression	[34]
Sphingomyelin phosphodiesterase 3 (SMPD3)	OTHQBETH	NSMA2_HUMAN	Decreases Expression	[35]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult acute myeloid leukemia	DCYS8YP	HL-60(TB)	Investigative	[1]
Adult T acute lymphoblastic leukemia	DC26IKP	MOLT-4	Investigative	[1]
Childhood T acute lymphoblastic leukemia	DCFV82K	CCRF-CEM	Investigative	[1]
Clear cell renal cell carcinoma	DCQN5TX	786-0	Investigative	[1]
Clear cell renal cell carcinoma	DC9G5VL	CAKI-1	Investigative	[1]
Glioma	DCONS86	SF-268	Investigative	[1]
Glioma	DCVGRT7	SF-539	Investigative	[1]
Plasma cell myeloma	DCHE0MO	RPMI-8226	Investigative	[1]
Renal cell carcinoma	DCU0MML	SN12C	Investigative	[1]
Renal cell carcinoma	DCLYTBH	UO-31	Investigative	[1]
Invasive ductal carcinoma	DCRLIJ9	BT-549	Investigative	[36]
Invasive ductal carcinoma	DCH7VUS	HS 578T	Investigative	[36]
Adenocarcinoma	DCSXTZE	HCC-2998	Investigative	[37]
Adenocarcinoma	DCCVVD5	HCT116	Investigative	[37]
Adenocarcinoma	DCBBS3R	SW-620	Investigative	[37]
High grade ovarian serous adenocarcinoma	DC18PVF	OVCAR-4	Investigative	[37]
High grade ovarian serous adenocarcinoma	DCLGJ22	OVCAR-5	Investigative	[37]
Large cell lung carcinoma	DCM1C07	NCI-H460	Investigative	[37]
Lung adenocarcinoma	DCX2ICZ	HOP-62	Investigative	[37]
Lung adenocarcinoma	DC4US7Z	NCI-H522	Investigative	[37]
Malignant melanoma	DCWAI88	UACC62	Investigative	[37]
Melanoma	DCWMPLW	MALME-3M	Investigative	[37]
Melanoma	DCN6AZO	SK-MEL-2	Investigative	[37]
Mixed endometrioid and clear cell carcinoma	DCFR43N	IGROV1	Investigative	[37]
Non-small cell lung carcinoma	DCL2RVI	HOP-92	Investigative	[37]

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