Details of the Drug Combination

General Information of Drug Combination (ID: DCBO84A)

• Drug Combination Name: Clofibrate + Idarubicin
• Indication: Glioblastoma?; Status: Investigative [1]
• Component Drugs:
  Clofibrate (DMPC1J7): Small molecular drug
  Idarubicin (DMM0XGL): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: T98G
  Zero Interaction Potency (ZIP) Score: 10.98
  Bliss Independence Score: 10.98
  Loewe Additivity Score: 5.7
  LHighest Single Agent (HSA) Score: 5.7

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Clofibrate

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

Clofibrate Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Lipoprotein lipase (LPL)	TTOF3WZ	LIPL_HUMAN	Activator	[5]

Clofibrate Interacts with 9 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[6]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[7]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Metabolism	[7]
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Metabolism	[7]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[7]
Glutathione S-transferase alpha-1 (GSTA1)	DE4ZHS1	GSTA1_HUMAN	Metabolism	[8]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[7]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[7]
Lauric acid omega-hydroxylase (CYP4A11)	DE2XQGW	CP4AB_HUMAN	Metabolism	[9]

Clofibrate Interacts with 18 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 4A11 (CYP4A11)	OTPU5J0S	CP4AB_HUMAN	Increases Expression	[10]
Carnitine O-palmitoyltransferase 1, liver isoform (CPT1A)	OTI862QH	CPT1A_HUMAN	Increases Expression	[11]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[12]
Phospholipid-transporting ATPase ABCA1 (ABCA1)	OT94G6BQ	ABCA1_HUMAN	Increases Expression	[13]
Ceruloplasmin (CP)	OTM8JE4Y	CERU_HUMAN	Decreases Expression	[14]
Antithrombin-III (SERPINC1)	OTDFATG0	ANT3_HUMAN	Decreases Expression	[15]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[16]
Pro-glucagon (GCG)	OTXU08VF	GLUC_HUMAN	Affects Secretion	[17]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Increases Expression	[14]
Serotransferrin (TF)	OT41PEMS	TRFE_HUMAN	Increases Expression	[14]
Transcriptional activator Myb (MYB)	OTJH64IV	MYB_HUMAN	Decreases Expression	[18]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Expression	[16]
G1/S-specific cyclin-D2 (CCND2)	OTDULQF9	CCND2_HUMAN	Decreases Expression	[18]
Microsomal triglyceride transfer protein large subunit (MTTP)	OTNUVSDT	MTP_HUMAN	Decreases Expression	[19]
Nuclear receptor subfamily 1 group I member 3 (NR1I3)	OTS3SGH7	NR1I3_HUMAN	Increases Activity	[20]
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A)	OTHCDQ22	PRGC1_HUMAN	Increases Expression	[19]
Phosphatidylcholine transfer protein (PCTP)	OTM36JXE	PPCT_HUMAN	Affects Localization	[21]
Nuclear receptor coactivator 1 (NCOA1)	OTLIUJQD	NCOA1_HUMAN	Affects Response To Substance	[16]

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	[23]

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	[24]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[25]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[25]

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	[26]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[26]

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	[27]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Decreases Activity	[22]

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: 2667).
• [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).
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• [15] Venous thrombosis, heparin-induced antithrombin III deficiency, and factor VIII. Lancet. 1977 Dec 10;2(8050):1231-2.
• [16] Steroid receptor coactivator 1 deficiency increases MMTV-neu mediated tumor latency and differentiation specific gene expression, decreases metastasis, and inhibits response to PPAR ligands. BMC Cancer. 2010 Nov 16;10:629. doi: 10.1186/1471-2407-10-629.
• [17] Glucagon secretion in primary endogenous hypertriglyceridemia before and after clofibrate treatment. Metabolism. 1975 Aug;24(8):901-14. doi: 10.1016/0026-0495(75)90081-5.
• [18] Peroxisome proliferator-activated receptor ligands affect growth-related gene expression in human leukemic cells. J Pharmacol Exp Ther. 2003 Jun;305(3):932-42. doi: 10.1124/jpet.103.049098. Epub 2003 Mar 20.
• [19] Advantageous use of HepaRG cells for the screening and mechanistic study of drug-induced steatosis. Toxicol Appl Pharmacol. 2016 Jul 1;302:1-9. doi: 10.1016/j.taap.2016.04.007. Epub 2016 Apr 16.
• [20] Agonistic effects of diverse xenobiotics on the constitutive androstane receptor as detected in a recombinant yeast-cell assay. Toxicol In Vitro. 2018 Feb;46:335-349. doi: 10.1016/j.tiv.2017.09.014. Epub 2017 Sep 18.
• [21] Clofibrate-induced relocation of phosphatidylcholine transfer protein to mitochondria in endothelial cells. Exp Cell Res. 2002 Mar 10;274(1):100-11. doi: 10.1006/excr.2001.5460.
• [22] 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.
• [23] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [24] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [25] Amonafide L-malate is not a substrate for multidrug resistance proteins in secondary acute myeloid leukemia. Leukemia. 2008 Nov;22(11):2110-5.
• [26] In vitro evaluation of cytochrome P450-mediated drug interactions between cytarabine, idarubicin, itraconazole and caspofungin. Hematology. 2004 Jun;9(3):217-21.
• [27] The use of biochemical markers in cardiotoxicity monitoring in patients treated for leukemia. Neoplasma. 2005;52(5):430-4.