Details of the Drug Combination

General Information of Drug Combination (ID: DCAMU99)

• Drug Combination Name: Levamisole + Mesalazine
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Levamisole (DM5EN79): Small molecular drug
  Mesalazine (DMOL5IU): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 66.27
  Bliss Independence Score: 66.27
  Loewe Additivity Score: 80.75
  LHighest Single Agent (HSA) Score: 80.76

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Levamisole

Disease Entry	ICD 11	Status	REF
Parasitic infection	1D0Y-1G2Z	Approved	[2]
Colon cancer	2B90.Z	Withdrawn from market	[3]

Levamisole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Alkaline phosphatase tissue-nonspecific (ALPL)	TTMR5UV	PPBT_HUMAN	Inhibitor	[8]

Levamisole Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Decreases Expression	[9]
Endothelin-1 (EDN1)	OTZCACEG	EDN1_HUMAN	Decreases Expression	[9]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Expression	[9]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[9]
Clusterin (CLU)	OTQGG0JM	CLUS_HUMAN	Decreases Expression	[9]
Nitric oxide synthase 3 (NOS3)	OTLDT7NR	NOS3_HUMAN	Decreases Expression	[9]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Increases Expression	[9]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Expression	[10]

Indication(s) of Mesalazine

Disease Entry	ICD 11	Status	REF
Diverticulitis	N.A.	Approved	[4]
Proctitis	DB33.Z	Approved	[5]
Ulcerative colitis	DD71	Approved	[6]
Ulcerative proctosigmoiditis	N.A.	Approved	[7]

Mesalazine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Prostaglandin G/H synthase 1 (COX-1)	TT8NGED	PGH1_HUMAN	Inhibitor	[11]

Mesalazine Interacts with 4 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[12]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[13]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[13]
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[13]

Mesalazine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
RNA cytidine acetyltransferase (hALP)	DEZV4AP	NAT10_HUMAN	Metabolism	[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] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] 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: 7210).
• [4] Colonic diverticular disease. Nat Rev Dis Primers. 2020 Mar 26;6(1):20.
• [5] Optimized Management of Ulcerative Proctitis: When and How to Use Mesalazine Suppository. Digestion. 2018;97(1):59-63.
• [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: 4655).
• [7] Efficacy of Oral, Topical, or Combined Oral and Topical 5-Aminosalicylates, in Ulcerative Colitis: Systematic Review and Network Meta-analysis. J Crohns Colitis. 2021 Jul 5;15(7):1184-1196.
• [8] Characterization of rat heart alkaline phosphatase isoenzymes and modulation of activity. Braz J Med Biol Res. 2008 Jul;41(7):600-9.
• [9] Levamisole induced apoptosis in cultured vascular endothelial cells. Br J Pharmacol. 2000 Dec;131(8):1577-83.
• [10] Levamisole can reduce the high serum tumour necrosis factor-alpha level to a normal level in patients with erosive oral lichen planus. Clin Exp Dermatol. 2007 May;32(3):308-10. doi: 10.1111/j.1365-2230.2006.02343.x.
• [11] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [12] Transport studies with 5-aminosalicylate. Eur J Clin Pharmacol. 2006 Oct;62(10):871-5.
• [13] Role of organic anion-transporting polypeptides for cellular mesalazine (5-aminosalicylic acid) uptake. Drug Metab Dispos. 2011 Jun;39(6):1097-102.
• [14] NAT1 genotypes do not predict response to mesalamine in patients with ulcerative colitis. Z Gastroenterol. 2008 Mar;46(3):259-65.