Details of the Drug Combination

General Information of Drug Combination (ID: DCJJ0K2)

• Drug Combination Name: Thioguanine + Vincristine
• Indication: Amelanotic melanoma; Status: Investigative [1]
• Component Drugs:
  Thioguanine (DM7NKEV): Small molecular drug
  Vincristine (DMINOX3): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: M14
  Zero Interaction Potency (ZIP) Score: 8.66
  Bliss Independence Score: 15.91
  Loewe Additivity Score: 14.4
  LHighest Single Agent (HSA) Score: 14.29

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 Vincristine

Disease Entry	ICD 11	Status	REF
Acute lymphoblastic leukaemia	2A85	Approved	[6]
Adult kidney Wilms tumor	N.A.	Approved	[7]
Beckwith-Wiedemann syndrome	N.A.	Approved	[7]
Burkitt lymphoma	N.A.	Approved	[7]
Central nervous system neoplasm	N.A.	Approved	[7]
Childhood acute lymphoblastic leukemia	N.A.	Approved	[7]
Childhood kidney Wilms tumor	N.A.	Approved	[7]
Hamartoma	N.A.	Approved	[7]
Kidney neoplasm	N.A.	Approved	[7]
Leukemia	N.A.	Approved	[7]
MALT lymphoma	N.A.	Approved	[7]
Nodal marginal zone lymphoma	2A85.0	Approved	[7]
Plasma cell myeloma	2A83.1	Approved	[7]
Primitive neuroectodermal tumor	N.A.	Approved	[7]
Splenic marginal zone lymphoma	N.A.	Approved	[7]
Testicular lymphoma	N.A.	Approved	[7]
Wilms tumor	N.A.	Approved	[7]
Classic Hodgkin lymphoma	N.A.	Investigative	[7]
Follicular lymphoma	2A80	Investigative	[7]
Neuroblastoma	2D11.2	Investigative	[7]

Vincristine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin beta (TUBB)	TTYFKSZ	NOUNIPROTAC	Modulator	[24]

Vincristine Interacts with 4 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[25]
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[26]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[27]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[28]

Vincristine Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[29]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[29]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[30]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult acute myeloid leukemia	DC6GEYF	HL-60(TB)	Investigative	[31]
Adult T acute lymphoblastic leukemia	DCVBM2B	MOLT-4	Investigative	[31]
Anaplastic large cell lymphoma	DCUMSR6	SR	Investigative	[31]
Childhood T acute lymphoblastic leukemia	DCV5SNH	CCRF-CEM	Investigative	[31]
Clear cell renal cell carcinoma	DC5QG4P	786-0	Investigative	[31]
Clear cell renal cell carcinoma	DC784KE	A498	Investigative	[31]
Clear cell renal cell carcinoma	DCQ2JU8	CAKI-1	Investigative	[31]
Glioma	DCGHNZD	SF-295	Investigative	[31]
Papillary renal cell carcinoma	DCAEDRB	ACHN	Investigative	[31]
Renal cell carcinoma	DC6LHLZ	SN12C	Investigative	[31]
Adenocarcinoma	DC2BBEM	DU-145	Investigative	[1]
Adenocarcinoma	DCUUJMY	OVCAR3	Investigative	[1]
Adenocarcinoma	DC2XM9J	A549	Investigative	[1]
Adenocarcinoma	DCL81ZA	HCT-15	Investigative	[1]
Cutaneous melanoma	DCDZ06U	SK-MEL-5	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCDKOS1	NCI\\/ADR-RES	Investigative	[1]
Large cell lung carcinoma	DCZJBJ8	NCI-H460	Investigative	[1]
Malignant melanoma	DCE9Z4Y	LOX IMVI	Investigative	[1]
Minimally invasive lung adenocarcinoma	DCMSZFP	NCI-H322M	Investigative	[1]
Mixed endometrioid and clear cell carcinoma	DCBJ9XD	IGROV1	Investigative	[1]
Non-small cell lung carcinoma	DC8PHJA	HOP-92	Investigative	[1]
Ovarian serous cystadenocarcinoma	DCSJBCD	SK-OV-3	Investigative	[1]

References

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• [3] Thioguanine FDA Label
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• [6] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6785).
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