Details of the Drug Combination

General Information of Drug Combination (ID: DCK7OSQ)

• Drug Combination Name: Cabazitaxel + Thioguanine
• Indication: Adult T acute lymphoblastic leukemia; Status: Investigative [1]
• Component Drugs:
  Cabazitaxel (DMPAZHC): Small molecular drug
  Thioguanine (DM7NKEV): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: MOLT-4
  Zero Interaction Potency (ZIP) Score: 9.63
  Bliss Independence Score: 6.27
  Loewe Additivity Score: 6.06
  LHighest Single Agent (HSA) Score: 8.36

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Cabazitaxel

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[2]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[2]
Metastatic prostate carcinoma	N.A.	Investigative	[3]

Cabazitaxel Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin (TUB)	TTML2WA	NOUNIPROTAC	Inhibitor	[8]

Cabazitaxel Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[9]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[9]

Cabazitaxel Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Forkhead box protein O3 (FOXO3)	OTHXQG4P	FOXO3_HUMAN	Affects Expression	[10]
Proline-rich AKT1 substrate 1 (AKT1S1)	OT4JHN4Y	AKTS1_HUMAN	Decreases Expression	[10]

Indication(s) of Thioguanine

Disease Entry	ICD 11	Status	REF
Acute lymphocytic leukaemia	2B33.3	Approved	[4]
Acute myelogenous leukaemia	2A41	Approved	[5]
Acute myeloid leukaemia	2A60	Approved	[6]
Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[7]
Severe acute respiratory syndrome (SARS)	1D65	Preclinical	[7]

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	[7]
Inosine-5'-monophosphate dehydrogenase (IMPDH)	TTCAQMW	NOUNIPROTAC	Intercalator	[11]
SARS-CoV papain-like proteinase (PL-PRO)	TTRGHB2	R1AB_CVHSA (819-2740)	Inhibitor	[7]

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	[12]
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[13]
Concentrative Na(+)-nucleoside cotransporter 3 (SLC28A3)	DT4YL5R	S28A3_HUMAN	Substrate	[14]

Thioguanine Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Thiopurine methyltransferase (TPMT)	DEFQ8VO	TPMT_HUMAN	Metabolism	[15]
Hypoxanthine phosphoribosyltransferase (HPRT1)	DEVXTP5	HPRT_HUMAN	Metabolism	[16]

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	[17]
Hypoxanthine-guanine phosphoribosyltransferase (HPRT1)	OTOEEEXG	HPRT_HUMAN	Decreases Response To Substance	[18]
Thiopurine S-methyltransferase (TPMT)	OTFOX70W	TPMT_HUMAN	Increases ADR	[19]
Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2)	OTPG0K7E	IMDH2_HUMAN	Increases Expression	[20]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Activity	[21]
Dystrophin (DMD)	OTD21T5J	DMD_HUMAN	Increases Splicing	[22]
Occludin (OCLN)	OTSUTVWL	OCLN_HUMAN	Decreases Activity	[23]
DNA mismatch repair protein Msh2 (MSH2)	OT10H1AB	MSH2_HUMAN	Increases Response To Substance	[24]
ATP-binding cassette sub-family C member 5 (ABCC5)	OT34G4US	MRP5_HUMAN	Decreases Response To Substance	[25]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Response To Substance	[21]
Baculoviral IAP repeat-containing protein 2 (BIRC2)	OTFXFREP	BIRC2_HUMAN	Decreases Response To Substance	[26]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCJ3WTV	DU-145	Investigative	[1]
Adenocarcinoma	DC7YHGP	HCT-15	Investigative	[1]
Adult acute myeloid leukemia	DCXAA9Z	HL-60(TB)	Investigative	[1]
Astrocytoma	DCWTKGK	SNB-19	Investigative	[1]
Childhood T acute lymphoblastic leukemia	DCDU9B9	CCRF-CEM	Investigative	[1]
Clear cell renal cell carcinoma	DCSMQXN	786-0	Investigative	[1]
Glioblastoma	DCELTPN	SNB-75	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCRMT68	NCI\\/ADR-RES	Investigative	[1]
Large cell lung carcinoma	DC988GF	NCI-H460	Investigative	[1]
Lung adenocarcinoma	DC3QTF6	HOP-62	Investigative	[1]
Ovarian serous cystadenocarcinoma	DC2635Q	SK-OV-3	Investigative	[1]
Papillary renal cell carcinoma	DCDW7QO	ACHN	Investigative	[1]
Renal cell carcinoma	DCMSYKF	SN12C	Investigative	[1]

References

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• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] Thioguanine FDA Label
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