Details of the Drug Combination

General Information of Drug Combination (ID: DC5AT0U)

• Drug Combination Name: Taxol + Ixabepilone
• Indication: Malignant melanoma; Status: Investigative [1]
• Component Drugs:
  Taxol (DMUOT9V): Small molecular drug
  Ixabepilone (DM2OZ3G): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: UACC62
  Zero Interaction Potency (ZIP) Score: 1.41
  Bliss Independence Score: 0.41
  Loewe Additivity Score: 1.53
  LHighest Single Agent (HSA) Score: 4.42

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 Ixabepilone

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[6]
Breast carcinoma	N.A.	Approved	[7]

Ixabepilone Interacts with 1 DTT Molecule(s)

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

Ixabepilone Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[9]

Ixabepilone Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[10]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult acute myeloid leukemia	DCEQJX2	HL-60(TB)	Investigative	[11]
Astrocytoma	DC797B8	SNB-19	Investigative	[11]
Chronic myelogenous leukemia	DCFS6SN	K-562	Investigative	[11]
Glioma	DCQ3I8Q	SF-539	Investigative	[11]
Renal cell carcinoma	DC8QC3O	SN12C	Investigative	[11]
Colon adenocarcinoma	DC87P8P	COLO 205	Investigative	[12]
Colon carcinoma	DCA2G0N	KM12	Investigative	[12]
Invasive ductal carcinoma	DC5U5XG	T-47D	Investigative	[12]
Adenocarcinoma	DCGXSWR	DU-145	Investigative	[1]
Adenocarcinoma	DCY6EV0	A549	Investigative	[1]
Adenocarcinoma	DCR3171	SW-620	Investigative	[1]
Adenocarcinoma	DC3HERI	HT29	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC30OND	OVCAR-5	Investigative	[1]
Large cell lung carcinoma	DCSWR1P	NCI-H460	Investigative	[1]
Lung adenocarcinoma	DCXL5MF	NCI-H522	Investigative	[1]
Prostate carcinoma	DC33HGQ	PC-3	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] 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: 6824).
• [7] Ixabepilone FDA Label
• [8] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [9] Ixabepilone, a novel microtubule-targeting agent for breast cancer, is a substrate for P-glycoprotein (P-gp/MDR1/ABCB1) but not breast cancer resistance protein (BCRP/ABCG2). J Pharmacol Exp Ther. 2011 May;337(2):423-32.
• [10] The effect of ketoconazole on the pharmacokinetics and pharmacodynamics of ixabepilone: a first in class epothilone B analogue in late-phase clinical development. Clin Cancer Res. 2008 May 1;14(9):2701-9.
• [11] 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.
• [12] 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.