Details of the Drug Combination

General Information of Drug Combination (ID: DC1A0WG)

• Drug Combination Name: Ciprofibrate + Palonosetron
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Ciprofibrate (DMGC5DB): Small molecular drug
  Palonosetron (DMBHMOX): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 25.49
  Bliss Independence Score: 25.49
  Loewe Additivity Score: 39.35
  LHighest Single Agent (HSA) Score: 39.35

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Ciprofibrate

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

Ciprofibrate Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Peroxisome proliferator-activated receptor alpha (PPARA)	TTJ584C	PPARA_HUMAN	Agonist	[5]

Ciprofibrate Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[6]

Ciprofibrate Interacts with 5 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	[7]
Transcriptional activator Myb (MYB)	OTJH64IV	MYB_HUMAN	Decreases Expression	[8]
G1/S-specific cyclin-D2 (CCND2)	OTDULQF9	CCND2_HUMAN	Decreases Expression	[8]
Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1)	OTM0A0DY	ACOX1_HUMAN	Increases Expression	[9]
Perilipin-2 (PLIN2)	OTRXJ9UN	PLIN2_HUMAN	Increases Expression	[10]

Indication(s) of Palonosetron

Disease Entry	ICD 11	Status	REF
Nausea	MD90	Approved	[3]
Vomiting	MD90	Approved	[4]

Palonosetron Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
5-HT 3A receptor (HTR3A)	TTPC4TU	5HT3A_HUMAN	Antagonist	[11]

Palonosetron Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[12]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[13]

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: 3438).
• [3] 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: 7486).
• [4] Palonosetron FDA Label
• [5] Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J Biol Chem. 2000 Jun 2;275(22):16638-42.
• [6] Clinical pharmacokinetics of fibric acid derivatives (fibrates). Clin Pharmacokinet. 1998 Feb;34(2):155-62.
• [7] 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.
• [8] 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.
• [9] Fish oil and fenofibrate prevented phosphorylation-dependent hepatic sortilin 1 degradation in Western diet-fed mice. J Biol Chem. 2014 Aug 8;289(32):22437-49. doi: 10.1074/jbc.M114.548933. Epub 2014 Jul 1.
• [10] Role of Peroxisome Proliferator-Activated Receptor / and B-Cell Lymphoma-6 in Regulation of Genes Involved in Metastasis and Migration in Pancreatic Cancer Cells. PPAR Res. 2013;2013:121956. doi: 10.1155/2013/121956. Epub 2013 May 2.
• [11] Management of postoperative nausea and vomiting: focus on palonosetron. Ther Clin Risk Manag. 2009 Feb;5(1):21-34.
• [12] Pharmacokinetics, metabolism and excretion of intravenous [l4C]-palonosetron in healthy human volunteers. Biopharm Drug Dispos. 2004 Nov;25(8):329-37.
• [13] Cytochrome P450 2D6 metabolism and 5-hydroxytryptamine type 3 receptor antagonists for postoperative nausea and vomiting. Med Sci Monit. 2005 Oct;11(10):RA322-8.