Details of the Drug Combination

General Information of Drug Combination (ID: DCC3X4H)

• Drug Combination Name: Galantamine + Fenoprofen
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Galantamine (DMEO794): Small molecular drug
  Fenoprofen (DML5VQ0): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 4.53
  Bliss Independence Score: 4.53
  Loewe Additivity Score: 19.72
  LHighest Single Agent (HSA) Score: 19.74

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Galantamine

Disease Entry	ICD 11	Status	REF
Alzheimer disease	8A20	Approved	[2]
Traumatic brain injury	NA07.Z	Approved	[3]

Galantamine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Acetylcholinesterase (AChE)	TT1RS9F	ACES_HUMAN	Inhibitor	[6]

Galantamine Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[7]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[7]

Galantamine Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cholinesterase (BCHE)	OTOH3WQ9	CHLE_HUMAN	Decreases Activity	[8]
Cocaine esterase (CES2)	OTC647SQ	EST2_HUMAN	Decreases Activity	[9]
Neuronal acetylcholine receptor subunit beta-2 (CHRNB2)	OTNAT2M5	ACHB2_HUMAN	Affects Binding	[10]
Acetylcholinesterase (ACHE)	OT2H8HG6	ACES_HUMAN	Decreases Activity	[11]
Neuronal acetylcholine receptor subunit alpha-4 (CHRNA4)	OT1H0ZXC	ACHA4_HUMAN	Affects Binding	[10]

Indication(s) of Fenoprofen

Disease Entry	ICD 11	Status	REF
Osteoarthritis	FA00-FA05	Approved	[4]
Pain	MG30-MG3Z	Approved	[4]
Rheumatoid arthritis	FA20	Approved	[5]

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	[14]

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	[14]
Prostaglandin reductase 1 (PTGR1)	OTMAR351	PTGR1_HUMAN	Affects Activity	[15]
HLA class II histocompatibility antigen, DQ beta 1 chain (HLA-DQB1)	OTVVI3UI	DQB1_HUMAN	Affects Expression	[16]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[17]
HLA class II histocompatibility antigen, DP alpha 1 chain (HLA-DPA1)	OT7OG7Y2	DPA1_HUMAN	Affects Expression	[16]
Dehydrogenase/reductase SDR family member 11 (DHRS11)	OTU3J0ZL	DHR11_HUMAN	Decreases Activity	[18]

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: 6693).
• [3] Galantamine FDA Label
• [4] Fenoprofen FDA Label
• [5] 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).
• [6] [From symptomatic to disease modifying therapy Recent developments in the pharmacotherapy of Alzheimer's disease]. Fortschr Neurol Psychiatr. 2009 Jun;77(6):326-33.
• [7] Clinical pharmacokinetics of galantamine. Clin Pharmacokinet. 2003;42(15):1383-92.
• [8] Lichens of parmelioid clade as promising multitarget neuroprotective agents. Chem Res Toxicol. 2019 Jun 17;32(6):1165-1177.
• [9] Inhibition of human carboxylesterases hCE1 and hiCE by cholinesterase inhibitors. Chem Biol Interact. 2013 Mar 25;203(1):226-30.
• [10] Cholinergic drugs potentiate human nicotinic alpha4beta2 acetylcholine receptors by a competitive mechanism. Eur J Pharmacol. 2005 Feb 21;509(2-3):97-108. doi: 10.1016/j.ejphar.2004.12.037.
• [11] Potencies and selectivities of inhibitors of acetylcholinesterase and its molecular forms in normal and Alzheimer's disease brain. Acta Biol Hung. 2003;54(2):183-9. doi: 10.1556/ABiol.54.2003.2.7.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] Human prostaglandin reductase 1 (PGR1): Substrate specificity, inhibitor analysis and site-directed mutagenesis. Chem Biol Interact. 2015 Jun 5;234:105-13.
• [16] 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.
• [17] 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.
• [18] 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.