Details of the Drug Combination

General Information of Drug Combination (ID: DC0QVET)

• Drug Combination Name: Rufinamide + Olmesartan medoxomil
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Rufinamide (DMWE60C): Small molecular drug
  Olmesartan medoxomil (DMWBHRY): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 14.49
  Bliss Independence Score: 14.49
  Loewe Additivity Score: 27.83
  LHighest Single Agent (HSA) Score: 27.85

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Rufinamide

Disease Entry	ICD 11	Status	REF
Epilepsy	8A60-8A68	Approved (orphan drug)	[2]
Pediatric lennox-gastaut syndrome	8A62.1	Approved	[3]
Seizure disorder	8A6Z	Approved	[2]

Rufinamide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Sodium channel unspecific (NaC)	TTRK8B9	NOUNIPROTAC	Blocker	[5]

Rufinamide Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Carboxylesterase 1 (CES1)	DEB30C5	EST1_HUMAN	Metabolism	[6]
Carboxylesterase 2 (CES2)	DETHCPD	EST2_HUMAN	Metabolism	[6]

Indication(s) of Olmesartan medoxomil

Disease Entry	ICD 11	Status	REF
High blood pressure	BA00	Approved	[4]

Olmesartan medoxomil Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Angiotensin II receptor type-1 (AGTR1)	TT8DBY3	AGTR1_HUMAN	Antagonist	[7]

Olmesartan medoxomil Interacts with 8 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[8]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[9]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[10]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[11]
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[8]
Organic anion transporter 1 (SLC22A6)	DTQ23VB	S22A6_HUMAN	Substrate	[8]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[8]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[8]

Olmesartan medoxomil Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[12]
Tight junction protein ZO-1 (TJP1)	OTBDCUPK	ZO1_HUMAN	Affects Localization	[13]

References

• [1] 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.
• [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: 7470).
• [3] Clinical pipeline report, company report or official report of Eisai.
• [4] Effect of angiotensin receptor blockade on endothelial function: focus on olmesartan medoxomil. Vasc Health Risk Manag. 2009;5(1):301-14.
• [5] Emerging drugs for epilepsy. Expert Opin Emerg Drugs. 2007 Sep;12(3):407-22.
• [6] Investigation of the metabolism of rufinamide and its interaction with valproate. Drug Metab Lett. 2011 Dec;5(4):280-9.
• [7] Mechanism of diastolic stiffening of the failing myocardium and its prevention by angiotensin receptor and calcium channel blockers. J Cardiovasc Pharmacol. 2009 Jul;54(1):47-56.
• [8] Multiple human isoforms of drug transporters contribute to the hepatic and renal transport of olmesartan, a selective antagonist of the angiotensin II AT1-receptor. Drug Metab Dispos. 2007 Dec;35(12):2166-76.
• [9] KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01665)
• [10] KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01913)
• [11] OATP1B1, OATP1B3, and mrp2 are involved in hepatobiliary transport of olmesartan, a novel angiotensin II blocker. Drug Metab Dispos. 2006 May;34(5):862-9.
• [12] A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
• [13] Immunopathogenesis of olmesartan-associated enteropathy. Aliment Pharmacol Ther. 2015 Dec;42(11-12):1303-14. doi: 10.1111/apt.13413. Epub 2015 Oct 1.