Details of the Drug Combination

General Information of Drug Combination (ID: DCLLTLN)

• Drug Combination Name: Methylene blue + Idarubicin
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Methylene blue (DMJAPE7): N.A.
  Idarubicin (DMM0XGL): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 1.32
  Bliss Independence Score: 1.32
  Loewe Additivity Score: 3.05
  LHighest Single Agent (HSA) Score: 3.08

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Methylene blue

Disease Entry	ICD 11	Status	REF
Acquired methemoglobinemia	3A93	Approved	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[3]

Methylene blue Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Monoamine oxidase (MAO)	TT32XQJ	NOUNIPROTAC	.	[6]
Guanylate cyclase (GC)	TT6HPVC	NOUNIPROTAC	Inhibitor	[7]

Methylene blue Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
6-phosphogluconate dehydrogenase, decarboxylating (PGD)	OTVG296F	6PGD_HUMAN	Increases Activity	[8]

Indication(s) of Idarubicin

Disease Entry	ICD 11	Status	REF
Acute myelogenous leukaemia	2A41	Approved	[4]
Acute myeloid leukaemia	2A60	Approved	[5]
Adult acute monocytic leukemia	N.A.	Approved	[4]
Childhood acute megakaryoblastic leukemia	N.A.	Approved	[4]
Leukemia	N.A.	Approved	[4]

Idarubicin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
DNA topoisomerase II (TOP2)	TT0IHXV	TOP2A_HUMAN; TOP2B_HUMAN	Modulator	[10]

Idarubicin Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[11]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[12]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[12]

Idarubicin Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[13]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[13]

Idarubicin Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Natriuretic peptides B (NPPB)	OTSN2IPY	ANFB_HUMAN	Increases Expression	[14]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Decreases Activity	[9]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [2] Recombinant Plasmodium falciparum glutathione reductase is inhibited by the antimalarial dye methylene blue. FEBS Lett. 1998 Feb 6;422(3):311-4.
• [3] ClinicalTrials.gov (NCT04370288) Clinical Application of Methylene Blue for Treatment of Covid-19 Patients. U.S. National Institutes of Health.
• [4] Idarubicin 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: 7083).
• [6] Photoluminescence of CdTe nanocrystals modulated by methylene blue and DNA. A label-free luminescent signaling nanohybrid platform. Phys Chem Chem Phys. 2009 Jul 7;11(25):5062-9.
• [7] Curcumin ameliorates high glucose-induced acute vascular endothelial dysfunction in rat thoracic aorta. Clin Exp Pharmacol Physiol. 2009 Dec;36(12):1177-82.
• [8] Defenses against oxidation in human erythrocytes: role of glutathione reductase in the activation of glucose decarboxylation by hemolytic drugs. J Lab Clin Med. 1991 Apr;117(4):325-31.
• [9] Quantitative high-throughput profiling of environmental chemicals and drugs that modulate farnesoid X receptor. Sci Rep. 2014 Sep 26;4:6437. doi: 10.1038/srep06437.
• [10] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [11] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [12] Amonafide L-malate is not a substrate for multidrug resistance proteins in secondary acute myeloid leukemia. Leukemia. 2008 Nov;22(11):2110-5.
• [13] In vitro evaluation of cytochrome P450-mediated drug interactions between cytarabine, idarubicin, itraconazole and caspofungin. Hematology. 2004 Jun;9(3):217-21.
• [14] The use of biochemical markers in cardiotoxicity monitoring in patients treated for leukemia. Neoplasma. 2005;52(5):430-4.