Details of the Drug Combination

General Information of Drug Combination (ID: DCLN0OZ)

• Drug Combination Name: Valrubicin + Ixabepilone
• Indication: Adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Valrubicin (DMOYJFK): Small molecular drug
  Ixabepilone (DM2OZ3G): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HCC-2998
  Zero Interaction Potency (ZIP) Score: 3.92
  Bliss Independence Score: 3.24
  Loewe Additivity Score: 3.48
  LHighest Single Agent (HSA) Score: 6.93

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Valrubicin

Disease Entry	ICD 11	Status	REF
Bladder cancer	2C94	Approved	[2]
In situ carcinoma	N.A.	Approved	[3]
Urinary bladder cancer	N.A.	Approved	[3]
Psoriasis vulgaris	EA90	Phase 2	[4]

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	[7]

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	[8]

Indication(s) of Ixabepilone

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[5]
Breast carcinoma	N.A.	Approved	[6]

Ixabepilone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin (TUB)	TTML2WA	NOUNIPROTAC	Stablizer	[9]

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	[10]

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	[11]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Astrocytoma	DCKPWPI	U251	Investigative	[12]
Glioma	DCZDB1U	SF-295	Investigative	[12]
Colon carcinoma	DCVQ11N	KM12	Investigative	[13]
Adenocarcinoma	DC5K6H1	NCIH23	Investigative	[1]
Adenocarcinoma	DCO7P2R	HT29	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] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [3] Valrubicin FDA Label
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] 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).
• [6] Ixabepilone FDA Label
• [7] Metabolic activation of N-acylanthracyclines precedes their interaction with DNA topoisomerase II. NCI Monogr. 1987;(4):111-5.
• [8] A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
• [9] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] 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.