Details of the Drug Combination

General Information of Drug Combination (ID: DCONUPQ)

• Drug Combination Name: Gemfibrozil + Idarubicin
• Indication: Glioblastoma?; Status: Investigative [1]
• Component Drugs:
  Gemfibrozil (DMD8Q3J): Small molecular drug
  Idarubicin (DMM0XGL): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: T98G
  Zero Interaction Potency (ZIP) Score: 18.99
  Bliss Independence Score: 18.99
  Loewe Additivity Score: 5.38
  LHighest Single Agent (HSA) Score: 5.38

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Gemfibrozil

Disease Entry	ICD 11	Status	REF
Hyperlipidaemia	5C80	Approved	[2]

Gemfibrozil Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Lipoprotein lipase (LPL)	TTOF3WZ	LIPL_HUMAN	Activator	[6]

Gemfibrozil Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[7]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[8]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[8]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Metabolism	[9]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Metabolism	[8]
Catechol-2,3-dioxygenase (caD)	DEFKSVZ	A0A371SLU3_9BACI	Metabolism	[10]

Gemfibrozil Interacts with 3 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Aldo-keto reductase family 1 member B10 (AKR1B10)	OTOA4HTH	AK1BA_HUMAN	Decreases Activity	[11]
Phospholipid-transporting ATPase ABCA1 (ABCA1)	OT94G6BQ	ABCA1_HUMAN	Increases Expression	[12]
Plasminogen activator inhibitor 1 (SERPINE1)	OTT0MPQ3	PAI1_HUMAN	Decreases Expression	[13]

Indication(s) of Idarubicin

Disease Entry	ICD 11	Status	REF
Acute myelogenous leukaemia	2A41	Approved	[3]
Acute myeloid leukaemia	2A60	Approved	[4]
Adult acute monocytic leukemia	N.A.	Approved	[3]
Childhood acute megakaryoblastic leukemia	N.A.	Approved	[3]
Leukemia	N.A.	Approved	[3]

Idarubicin 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	Modulator	[15]

Idarubicin Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[16]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[17]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[17]

Idarubicin Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[18]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[18]

Idarubicin Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Natriuretic peptides B (NPPB)	OTSN2IPY	ANFB_HUMAN	Increases Expression	[19]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Decreases Activity	[14]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [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: 3439).
• [3] Idarubicin FDA Label
• [4] 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: 7083).
• [5] Comparative effects of fibrates on drug metabolizing enzymes in human hepatocytes. Pharm Res. 2005 Jan;22(1):71-8.
• [6] Mode of action of fibrates in the regulation of triglyceride and HDL-cholesterol metabolism. Drugs Today (Barc). 2006 Jan;42(1):39-64.
• [7] Clinical pharmacokinetics of fibric acid derivatives (fibrates). Clin Pharmacokinet. 1998 Feb;34(2):155-62.
• [8] The UDP-glucuronosyltransferase 2B7 isozyme is responsible for gemfibrozil glucuronidation in the human liver. Drug Metab Dispos. 2007 Nov;35(11):2040-4.
• [9] Comprehensive pharmacogenomic study reveals an important role of UGT1A3 in montelukast pharmacokinetics. Clin Pharmacol Ther. 2018 Jul;104(1):158-168.
• [10] Genomic, proteomic, and metabolite characterization of gemfibrozil-degrading organism Bacillus sp. GeD10. Environ Sci Technol. 2016 Jan 19;50(2):744-55.
• [11] Inhibiting wild-type and C299S mutant AKR1B10; a homologue of aldose reductase upregulated in cancers. Eur J Pharmacol. 2008 Apr 28;584(2-3):213-21.
• [12] On the mechanism for PPAR agonists to enhance ABCA1 gene expression. Atherosclerosis. 2009 Aug;205(2):413-9. doi: 10.1016/j.atherosclerosis.2009.01.008. Epub 2009 Jan 19.
• [13] Effects of fibrate compounds on expression of plasminogen activator inhibitor-1 by cultured endothelial cells. Arterioscler Thromb Vasc Biol. 1999 Jun;19(6):1577-81. doi: 10.1161/01.atv.19.6.1577.
• [14] Quantitative high-throughput profiling of environmental chemicals and drugs that modulate farnesoid X receptor. Sci Rep. 2014 Sep 26;4:6437. doi: 10.1038/srep06437.
• [15] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [16] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [17] Amonafide L-malate is not a substrate for multidrug resistance proteins in secondary acute myeloid leukemia. Leukemia. 2008 Nov;22(11):2110-5.
• [18] In vitro evaluation of cytochrome P450-mediated drug interactions between cytarabine, idarubicin, itraconazole and caspofungin. Hematology. 2004 Jun;9(3):217-21.
• [19] The use of biochemical markers in cardiotoxicity monitoring in patients treated for leukemia. Neoplasma. 2005;52(5):430-4.