Details of the Drug Combination

General Information of Drug Combination (ID: DC9T5VT)

Drug Combination Name

Taxol GSK525762

Indication

Disease Entry	Status	REF
Breast and ovarian cancer syndrome	Investigative	[1]

Component Drugs

Taxol DMUOT9V

GSK525762 DMPAWBN

Small molecular drug

2D MOL

3D MOL is unavailable

High-throughput Screening Result

Testing Cell Line: UWB1289+BRCA1

Zero Interaction Potency (ZIP) Score: 3.76

Bliss Independence Score: 2.79

Loewe Additivity Score: 1

LHighest Single Agent (HSA) Score: 2.68

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Taxol

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[2]
Solid tumour/cancer	2A00-2F9Z	Approved	[3]
Pancreatic cancer	2C10	Phase 3	[4]
Gastric adenocarcinoma	2B72	Phase 2	[5]
Ovarian cancer	2C73	Phase 2	[5]

Taxol Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Apoptosis regulator Bcl-2 (BCL-2)	TTJGNVC	BCL2_HUMAN	Modulator	[2]
Tubulin beta (TUBB)	TTYFKSZ	NOUNIPROTAC	Modulator	[2]
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Indication(s) of GSK525762

Disease Entry	ICD 11	Status	REF
Haematological malignancy	2B33.Y	Phase 1	[4]
Solid tumour/cancer	2A00-2F9Z	Phase 1	[6]

GSK525762 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bromodomain-containing protein 4 (BRD4)	TTRA6BO	BRD4_HUMAN	Modulator	[8]
Bromodomain and extraterminal domain protein (BET)	TTE4BSY	NOUNIPROTAC	Inhibitor	[4]
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GSK525762 Interacts with 11 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Apolipoprotein A-I (APOA1)	OT5THARI	APOA1_HUMAN	Increases Expression	[9]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Decreases Expression	[10]
Trefoil factor 1 (TFF1)	OTCYQH4F	TFF1_HUMAN	Decreases Expression	[10]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[10]
Protein-lysine 6-oxidase (LOX)	OT1C2HIU	LYOX_HUMAN	Decreases Expression	[7]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[11]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[11]
Carbonic anhydrase 9 (CA9)	OTNA51XT	CAH9_HUMAN	Decreases Expression	[7]
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3)	OT25JBA3	F263_HUMAN	Increases Expression	[7]
Protein GREB1 (GREB1)	OTU6ZA26	GREB1_HUMAN	Decreases Expression	[10]
Endothelial PAS domain-containing protein 1 (EPAS1)	OTRE3O8U	EPAS1_HUMAN	Increases Expression	[7]
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⏷ Show the Full List of 11 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Breast and ovarian cancer syndrome	DCCEC9C	UWB1289	Investigative	[1]
Breast carcinoma	DC7I2LZ	OCUBM	Investigative	[1]
Carcinoma	DCM6X3U	MDAMB436	Investigative	[1]
Adenocarcinoma	DCQVT9F	COLO320DM	Investigative	[12]
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References

1	Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.
2	Paclitaxel directly binds to Bcl-2 and functionally mimics activity of Nur77. Cancer Res. 2009 Sep 1;69(17):6906-14.
3	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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: 7033).
7	The BET inhibitor JQ1 selectively impairs tumour response to hypoxia and downregulates CA9 and angiogenesis in triple negative breast cancer. Oncogene. 2017 Jan 5;36(1):122-132. doi: 10.1038/onc.2016.184. Epub 2016 Jun 13.
8	Targeting bromodomains: epigenetic readers of lysine acetylation.Nat Rev Drug Discov.2014 May;13(5):337-56.
9	Discovery and characterization of small molecule inhibitors of the BET family bromodomains. J Med Chem. 2011 Jun 9;54(11):3827-38.
10	An epigenomic approach to therapy for tamoxifen-resistant breast cancer. Cell Res. 2014 Jul;24(7):809-19. doi: 10.1038/cr.2014.71. Epub 2014 May 30.
11	MCM5 as a target of BET inhibitors in thyroid cancer cells. Endocr Relat Cancer. 2016 Apr;23(4):335-47. doi: 10.1530/ERC-15-0322. Epub 2016 Feb 24.
12	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.