Details of the Drug Combination

General Information of Drug Combination (ID: DCCJNQ5)

• Drug Combination Name: Taxol + Valrubicin
• Indication: Ovarian serous cystadenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Taxol (DMUOT9V): Small molecular drug: 3D MOL is unavailable
  Valrubicin (DMOYJFK): Small molecular drug: 3D MOL is unavailable
• High-throughput Screening Result:
  Testing Cell Line: SK-OV-3
  Zero Interaction Potency (ZIP) Score: 3.76
  Bliss Independence Score: 3.43
  Loewe Additivity Score: 0.54
  LHighest Single Agent (HSA) Score: 0.71

Molecular Interaction Atlas of This Drug Combination

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]

Indication(s) of Valrubicin

Disease Entry	ICD 11	Status	REF
Bladder cancer	2C94	Approved	[6]
In situ carcinoma	N.A.	Approved	[7]
Urinary bladder cancer	N.A.	Approved	[7]
Psoriasis vulgaris	EA90	Phase 2	[3]

Valrubicin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
DNA topoisomerase II (TOP2)	TT0IHXV	TOP2A_HUMAN; TOP2B_HUMAN	Inhibitor	[8]

Valrubicin Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[9]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Clear cell renal cell carcinoma	DCX25X5	786-0	Investigative	[10]
Renal cell carcinoma	DCRGN3L	SN12C	Investigative	[10]
Renal cell carcinoma	DCZ9XZY	UO-31	Investigative	[10]
Carcinoma	DCL0P2X	MCF7	Investigative	[11]
Amelanotic melanoma	DC8UHGE	MDA-MB-435	Investigative	[1]
Lung adenocarcinoma	DCQGXPE	EKVX	Investigative	[1]
Lung adenocarcinoma	DC6PCGW	HOP-62	Investigative	[1]

References

• [1] 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.
• [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] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [7] Valrubicin FDA Label
• [8] Metabolic activation of N-acylanthracyclines precedes their interaction with DNA topoisomerase II. NCI Monogr. 1987;(4):111-5.
• [9] A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
• [10] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [11] 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.