Details of the Drug Combination

General Information of Drug Combination (ID: DC6C989)

• Drug Combination Name: Lefaxin + Sivelestat
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Lefaxin (DM0CEY3): Small molecular drug
  Sivelestat (DM6BZCV): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 28.03
  Bliss Independence Score: 28.03
  Loewe Additivity Score: 43.92
  LHighest Single Agent (HSA) Score: 43.93

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Lefaxin

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[2]

Lefaxin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Coagulation factor Xa (F10)	TTCIHJA	FA10_HUMAN	Inhibitor	[2]

Lefaxin Interacts with 11 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Acetylcholinesterase (ACHE)	OT2H8HG6	ACES_HUMAN	Decreases Activity	[6]
Superoxide dismutase (SOD1)	OT39TA1L	SODC_HUMAN	Affects Expression	[7]
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Decreases Expression	[7]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Decreases Expression	[7]
Glutathione peroxidase 1 (GPX1)	OTE2O72Q	GPX1_HUMAN	Decreases Expression	[7]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[7]
DNA cytosine-5)-methyltransferase 1 (DNMT1)	OTM2DGTK	DNMT1_HUMAN	Decreases Expression	[7]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Decreases Expression	[7]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Decreases Expression	[7]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Decreases Expression	[7]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[8]

Indication(s) of Sivelestat

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

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	[9]
Neutrophil elastase (NE)	TTPLTSQ	ELNE_HUMAN	Inhibitor	[10]

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] Novel approaches to the treatment of thrombosis. Trends Pharmacol Sci. 2002 Jan;23(1):25-32.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [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] In vitro kinetic interactions of DEET, pyridostigmine and organophosphorus pesticides with human cholinesterases. Chem Biol Interact. 2011 Apr 25;190(2-3):79-83.
• [7] The Val16Ala-SOD2 polymorphism affects cyto-genotoxicity of pyridostigmine bromide on human peripheral blood mononuclear cells. Toxicol In Vitro. 2019 Oct;60:237-244.
• [8] Binding of pyridostigmine bromide, N,N-diethyl-m-toluamide and permethrin, alone and in combinations, to human serum albumin. Arch Toxicol. 2002 May;76(4):203-8. doi: 10.1007/s00204-002-0328-8. Epub 2002 Mar 9.
• [9] 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.
• [10] Neutrophil elastase inhibitor (sivelestat) reduces the levels of inflammatory mediators by inhibiting NF-kB. Inflamm Res. 2009 Apr;58(4):198-203.