Details of the Drug Combination

General Information of Drug Combination (ID: DCFE5YW)

• Drug Combination Name: Moricizine + Fenoprofen
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Moricizine (DMOMBJW): Small molecular drug
  Fenoprofen (DML5VQ0): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 9.89
  Bliss Independence Score: 9.89
  Loewe Additivity Score: 25.37
  LHighest Single Agent (HSA) Score: 25.39

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Moricizine

Disease Entry	ICD 11	Status	REF
Arrhythmia	BC9Z	Approved	[2]
Long QT syndrome	BC65.0	Approved	[3]
Heart arrhythmia	BC65	Withdrawn from market	[4]

Moricizine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Voltage-gated sodium channel alpha Nav1.5 (SCN5A)	TTZOVE0	SCN5A_HUMAN	Blocker	[7]

Moricizine Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[8]
Cytochrome P450 2B6 (CYP2B6)	OTOYO4S7	CP2B6_HUMAN	Increases Expression	[8]

Indication(s) of Fenoprofen

Disease Entry	ICD 11	Status	REF
Osteoarthritis	FA00-FA05	Approved	[5]
Pain	MG30-MG3Z	Approved	[5]
Rheumatoid arthritis	FA20	Approved	[6]

Fenoprofen Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Prostaglandin G/H synthase (COX)	TTK0943	PGH1_HUMAN; PGH2_HUMAN	Inhibitor	[11]

Fenoprofen Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Tumor necrosis factor receptor superfamily member 16 (NGFR)	OTPKSM49	TNR16_HUMAN	Increases Expression	[11]
Prostaglandin reductase 1 (PTGR1)	OTMAR351	PTGR1_HUMAN	Affects Activity	[12]
HLA class II histocompatibility antigen, DQ beta 1 chain (HLA-DQB1)	OTVVI3UI	DQB1_HUMAN	Affects Expression	[13]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[14]
HLA class II histocompatibility antigen, DP alpha 1 chain (HLA-DPA1)	OT7OG7Y2	DPA1_HUMAN	Affects Expression	[13]
Dehydrogenase/reductase SDR family member 11 (DHRS11)	OTU3J0ZL	DHR11_HUMAN	Decreases Activity	[15]

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] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] Moricizine 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: 7244).
• [5] Fenoprofen FDA Label
• [6] 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: 4820).
• [7] From first class to third class: recent upheaval in antiarrhythmic therapy--lessons from clinical trials. Am J Cardiol. 1996 Aug 29;78(4A):28-33.
• [8] Comparison of immortalized Fa2N-4 cells and human hepatocytes as in vitro models for cytochrome P450 induction. Drug Metab Dispos. 2008 Jun;36(6):1046-55.
• [9] Complementary deoxyribonucleic acid cloning and expression of a human liver uridine diphosphate-glucuronosyltransferase glucuronidating carboxylic acid-containing drugs. J Pharmacol Exp Ther. 1993 Jan;264(1):475-9.
• [10] Gastrointestinally distributed UDP-glucuronosyltransferase 1A10, which metabolizes estrogens and nonsteroidal anti-inflammatory drugs, depends upon phosphorylation. J Biol Chem. 2004 Jul 2;279(27):28320-9. doi: 10.1074/jbc.M401396200. Epub 2004 Apr 26.
• [11] The aryl propionic acid R-flurbiprofen selectively induces p75NTR-dependent decreased survival of prostate tumor cells. Cancer Res. 2007 Apr 1;67(7):3254-62.
• [12] Human prostaglandin reductase 1 (PGR1): Substrate specificity, inhibitor analysis and site-directed mutagenesis. Chem Biol Interact. 2015 Jun 5;234:105-13.
• [13] Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
• [14] A protein-coated magnetic beads as a tool for the rapid drug-protein binding study. J Pharm Biomed Anal. 2010 Jul 8;52(3):420-4. doi: 10.1016/j.jpba.2009.06.023. Epub 2009 Jun 18.
• [15] Rabbit dehydrogenase/reductase SDR family member 11 (DHRS11): Its identity with acetohexamide reductase with broad substrate specificity and inhibitor sensitivity, different from human DHRS11. Chem Biol Interact. 2019 May 25;305:12-20. doi: 10.1016/j.cbi.2019.03.026. Epub 2019 Mar 26.