Details of the Drug Combination

General Information of Drug Combination (ID: DCS8ROF)

• Drug Combination Name: Galantamine + Sivelestat
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Galantamine (DMEO794): Small molecular drug
  Sivelestat (DM6BZCV): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 3.94
  Bliss Independence Score: 3.94
  Loewe Additivity Score: 19.88
  LHighest Single Agent (HSA) Score: 19.9

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	[7]

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	[8]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[8]

Galantamine Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cholinesterase (BCHE)	OTOH3WQ9	CHLE_HUMAN	Decreases Activity	[9]
Cocaine esterase (CES2)	OTC647SQ	EST2_HUMAN	Decreases Activity	[10]
Neuronal acetylcholine receptor subunit beta-2 (CHRNB2)	OTNAT2M5	ACHB2_HUMAN	Affects Binding	[11]
Acetylcholinesterase (ACHE)	OT2H8HG6	ACES_HUMAN	Decreases Activity	[12]
Neuronal acetylcholine receptor subunit alpha-4 (CHRNA4)	OT1H0ZXC	ACHA4_HUMAN	Affects Binding	[11]

Indication(s) of Sivelestat

Disease Entry	ICD 11	Status	REF
Crohn disease	DD70	Phase 3	[4]
Multiple sclerosis	8A40	Phase 3	[4]
Psoriatic arthritis	FA21	Phase 3	[4]
Pyoderma gangrenosum	EB21	Phase 3	[5]
Rheumatoid arthritis	FA20	Phase 3	[4]
Ulcerative colitis	DD71	Phase 3	[4]
Anterior uveitis	9A96	Application submitted	[6]
Axial spondyloarthritis	FA92.0	Application submitted	[4]

Sivelestat Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Pancreatic elastase 1 (CELA1)	TT3NKIB	CELA1_HUMAN	Inhibitor	[13]
Neutrophil elastase (NE)	TTPLTSQ	ELNE_HUMAN	Inhibitor	[14]

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] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] [From symptomatic to disease modifying therapy Recent developments in the pharmacotherapy of Alzheimer's disease]. Fortschr Neurol Psychiatr. 2009 Jun;77(6):326-33.
• [8] Clinical pharmacokinetics of galantamine. Clin Pharmacokinet. 2003;42(15):1383-92.
• [9] Lichens of parmelioid clade as promising multitarget neuroprotective agents. Chem Res Toxicol. 2019 Jun 17;32(6):1165-1177.
• [10] Inhibition of human carboxylesterases hCE1 and hiCE by cholinesterase inhibitors. Chem Biol Interact. 2013 Mar 25;203(1):226-30.
• [11] 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.
• [12] 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.
• [13] Sivelestat (selective neutrophil elastase inhibitor) improves the mortality rate of sepsis associated with both acute respiratory distress syndrome... Shock. 2010 Jan;33(1):14-8.
• [14] Neutrophil elastase inhibitor (sivelestat) reduces the levels of inflammatory mediators by inhibiting NF-kB. Inflamm Res. 2009 Apr;58(4):198-203.