Details of the Drug Combination

General Information of Drug Combination (ID: DC5S5WD)

• Drug Combination Name: Thioguanine + Aminolevulinic Acid Hydrochloride
• Indication: Glioblastoma; Status: Investigative [1]
• Component Drugs:
  Thioguanine (DM7NKEV): Small molecular drug
  Aminolevulinic Acid Hydrochloride (DMWNHPC): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SNB-75
  Zero Interaction Potency (ZIP) Score: 1.5
  Bliss Independence Score: 5.76
  Loewe Additivity Score: 6.46
  LHighest Single Agent (HSA) Score: 7.79

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	[6]
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	[7]
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[8]
Concentrative Na(+)-nucleoside cotransporter 3 (SLC28A3)	DT4YL5R	S28A3_HUMAN	Substrate	[9]

Thioguanine Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Thiopurine methyltransferase (TPMT)	DEFQ8VO	TPMT_HUMAN	Metabolism	[10]
Hypoxanthine phosphoribosyltransferase (HPRT1)	DEVXTP5	HPRT_HUMAN	Metabolism	[11]

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	[12]
Hypoxanthine-guanine phosphoribosyltransferase (HPRT1)	OTOEEEXG	HPRT_HUMAN	Decreases Response To Substance	[13]
Thiopurine S-methyltransferase (TPMT)	OTFOX70W	TPMT_HUMAN	Increases ADR	[14]
Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2)	OTPG0K7E	IMDH2_HUMAN	Increases Expression	[15]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Activity	[16]
Dystrophin (DMD)	OTD21T5J	DMD_HUMAN	Increases Splicing	[17]
Occludin (OCLN)	OTSUTVWL	OCLN_HUMAN	Decreases Activity	[18]
DNA mismatch repair protein Msh2 (MSH2)	OT10H1AB	MSH2_HUMAN	Increases Response To Substance	[19]
ATP-binding cassette sub-family C member 5 (ABCC5)	OT34G4US	MRP5_HUMAN	Decreases Response To Substance	[20]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Response To Substance	[16]
Baculoviral IAP repeat-containing protein 2 (BIRC2)	OTFXFREP	BIRC2_HUMAN	Decreases Response To Substance	[21]

Indication(s) of Aminolevulinic Acid Hydrochloride

Disease Entry	ICD 11	Status	REF
Actinic keratosis	EK90.0	Approved	[2]

Aminolevulinic Acid Hydrochloride Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Protoporphyrinogen oxidase (PPOX)	TTNFMS9	PPOX_HUMAN	Modulator	[22]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult acute myeloid leukemia	DCF4TXI	HL-60(TB)	Investigative	[1]
Adult T acute lymphoblastic leukemia	DCHBK8K	MOLT-4	Investigative	[1]
Anaplastic large cell lymphoma	DCU4CR1	SR	Investigative	[1]
Astrocytoma	DCH6X5T	U251	Investigative	[1]
Childhood T acute lymphoblastic leukemia	DCWF2K0	CCRF-CEM	Investigative	[1]
Chronic myelogenous leukemia	DCMSYKV	K-562	Investigative	[1]
Clear cell renal cell carcinoma	DCOQM3I	A498	Investigative	[1]
Papillary renal cell carcinoma	DCNB60X	ACHN	Investigative	[1]
Plasma cell myeloma	DCB1AY8	RPMI-8226	Investigative	[1]
Renal cell carcinoma	DCH6A5K	SN12C	Investigative	[1]
Colon adenocarcinoma	DCR3QLE	COLO 205	Investigative	[23]
Invasive ductal carcinoma	DCSP9NQ	BT-549	Investigative	[23]
Adenocarcinoma	DCFQOFL	DU-145	Investigative	[24]
Adenocarcinoma	DCMKSER	NCIH23	Investigative	[24]
Amelanotic melanoma	DCBR7KS	MDA-MB-435	Investigative	[24]
Cutaneous melanoma	DCCBGPY	SK-MEL-5	Investigative	[24]
Large cell lung carcinoma	DC0PDLZ	NCI-H460	Investigative	[24]
Lung adenocarcinoma	DCO59D2	EKVX	Investigative	[24]
Malignant melanoma	DCZX7N9	LOX IMVI	Investigative	[24]
Melanoma	DC3X18O	SK-MEL-2	Investigative	[24]
Non-small cell lung carcinoma	DCXQ3EN	HOP-92	Investigative	[24]

References

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• [3] Thioguanine FDA Label
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• [15] Petit E, Langouet S, Akhdar H, Nicolas-Nicolaz C, Guillouzo A, Morel F. Differential toxic effects of azathioprine, 6-mercaptopurine and 6-thioguanine on human hepatocytes. Toxicol In Vitro. 2008;22(3):632-642. [PMID: 18222062]
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• [17] The effect of 6-thioguanine on alternative splicing and antisense-mediated exon skipping treatment for duchenne muscular dystrophy. PLoS Curr. 2012 Dec 12;4:ecurrents.md.597d700f92eaa70de261ea0d91821377. doi: 10.1371/currents.md.597d700f92eaa70de261ea0d91821377.
• [18] The thiopurine methyltransferase genetic polymorphism is associated with thioguanine-related veno-occlusive disease of the liver in children with acute lymphoblastic leukemia. Clin Pharmacol Ther. 2006 Oct;80(4):375-83. doi: 10.1016/j.clpt.2006.07.002.
• [19] The effect of Msh2 knockdown on methylating agent induced toxicity in DNA glycosylase deficient cells. Toxicology. 2010 Jan 31;268(1-2):111-7. doi: 10.1016/j.tox.2009.12.008. Epub 2009 Dec 16.
• [20] The multidrug resistance protein 5 (ABCC5) confers resistance to 5-fluorouracil and transports its monophosphorylated metabolites. Mol Cancer Ther. 2005 May;4(5):855-63.
• [21] Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res. 2000 May;6(5):1796-803.
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• [24] Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.