Details of the Drug Combination

General Information of Drug Combination (ID: DCWJ3V3)

• Drug Combination Name: Vincristine + Taxol
• Indication: High grade ovarian serous adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Vincristine (DMINOX3): Small molecular drug
  Taxol (DMUOT9V): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: OVCAR-8
  Zero Interaction Potency (ZIP) Score: 10.08
  Bliss Independence Score: 13.37
  Loewe Additivity Score: 0.52
  LHighest Single Agent (HSA) Score: 10.26

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Vincristine

Disease Entry	ICD 11	Status	REF
Acute lymphoblastic leukaemia	2A85	Approved	[2]
Adult kidney Wilms tumor	N.A.	Approved	[3]
Beckwith-Wiedemann syndrome	N.A.	Approved	[3]
Burkitt lymphoma	N.A.	Approved	[3]
Central nervous system neoplasm	N.A.	Approved	[3]
Childhood acute lymphoblastic leukemia	N.A.	Approved	[3]
Childhood kidney Wilms tumor	N.A.	Approved	[3]
Hamartoma	N.A.	Approved	[3]
Kidney neoplasm	N.A.	Approved	[3]
Leukemia	N.A.	Approved	[3]
MALT lymphoma	N.A.	Approved	[3]
Nodal marginal zone lymphoma	2A85.0	Approved	[3]
Plasma cell myeloma	2A83.1	Approved	[3]
Primitive neuroectodermal tumor	N.A.	Approved	[3]
Splenic marginal zone lymphoma	N.A.	Approved	[3]
Testicular lymphoma	N.A.	Approved	[3]
Wilms tumor	N.A.	Approved	[3]
Classic Hodgkin lymphoma	N.A.	Investigative	[3]
Follicular lymphoma	2A80	Investigative	[3]
Neuroblastoma	2D11.2	Investigative	[3]

Vincristine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin beta (TUBB)	TTYFKSZ	NOUNIPROTAC	Modulator	[8]

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	[9]
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[10]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[11]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[12]

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	[13]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[13]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[14]

Indication(s) of Taxol

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[4]
Solid tumour/cancer	2A00-2F9Z	Approved	[5]
Pancreatic cancer	2C10	Phase 3	[6]
Gastric adenocarcinoma	2B72	Phase 2	[7]
Ovarian cancer	2C73	Phase 2	[7]

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	[4]
Tubulin beta (TUBB)	TTYFKSZ	NOUNIPROTAC	Modulator	[4]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Chronic myelogenous leukemia	DCHO5GA	K-562	Investigative	[1]
Plasma cell myeloma	DC8XQFZ	RPMI-8226	Investigative	[1]

References

• [1] 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.
• [2] 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).
• [3] Vincristine FDA Label
• [4] Paclitaxel directly binds to Bcl-2 and functionally mimics activity of Nur77. Cancer Res. 2009 Sep 1;69(17):6906-14.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [9] Interaction of plant cannabinoids with the multidrug transporter ABCC1 (MRP1). Eur J Pharmacol. 2008 Sep 4;591(1-3):128-31.
• [10] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [11] L-type calcium channel blockers reverse docetaxel and vincristine-induced multidrug resistance independent of ABCB1 expression in human lung cancer cell lines. Toxicol Lett. 2010 Feb 15;192(3):408-18.
• [12] Mutant Gly482 and Thr482 ABCG2 mediate high-level resistance to lipophilic antifolates. Cancer Chemother Pharmacol. 2006 Dec;58(6):826-34.
• [13] Association of CYP3A5 expression and vincristine neurotoxicity in pediatric malignancies in Turkish population. J Pediatr Hematol Oncol. 2017 Aug;39(6):458-462.
• [14] Drug Interactions Flockhart Table