Details of the Drug Combination

General Information of Drug Combination (ID: DCXOZ0F)

• Drug Combination Name: Tindamax + Methylene blue
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Tindamax (DM3OWT4): Small molecular drug
  Methylene blue (DMJAPE7): N.A.
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 3.96
  Bliss Independence Score: 3.96
  Loewe Additivity Score: 4.66
  LHighest Single Agent (HSA) Score: 4.73

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Tindamax

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Approved	[2]
Bacterial vaginosis	MF3A	Approved	[3]
Trichomoniasis	N.A.	Approved	[4]
Giardiasis	N.A.	Investigative	[5]

Tindamax 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]
Nitroreductase (NTR)	DEAN5EW	NFSB_ENTCL	Metabolism	[9]

Tindamax Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[10]

Indication(s) of Methylene blue

Disease Entry	ICD 11	Status	REF
Acquired methemoglobinemia	3A93	Approved	[6]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[7]

Methylene blue Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Monoamine oxidase (MAO)	TT32XQJ	NOUNIPROTAC	.	[11]
Guanylate cyclase (GC)	TT6HPVC	NOUNIPROTAC	Inhibitor	[12]

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	[13]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [2] 2004 approvals: the demise of the blockbuster. Nat Rev Drug Discov. 2005 Feb;4(2):93-4.
• [3] Tinidazole. 2021 Mar 17. Drugs and Lactation Database (LactMed?) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development; 2006C.
• [4] Tinidazole (Tindamax)--a new option for treatment of bacterial vaginosis. Med Lett Drugs Ther. 2007 Sep 10;49(1269):73-4.
• [5] Tinidazole (Tindamax) - a new anti-protozoal drug. Med Lett Drugs Ther. 2004 Aug 30;46(1190):70-2.
• [6] Recombinant Plasmodium falciparum glutathione reductase is inhibited by the antimalarial dye methylene blue. FEBS Lett. 1998 Feb 6;422(3):311-4.
• [7] ClinicalTrials.gov (NCT04370288) Clinical Application of Methylene Blue for Treatment of Covid-19 Patients. U.S. National Institutes of Health.
• [8] FDA label of Tinidazole. The 2020 official website of the U.S. Food and Drug Administration.
• [9] Overexpression, isotopic labeling, and spectral characterization of Enterobacter cloacae nitroreductase. Protein Expr Purif. 1998 Jun;13(1):53-60.
• [10] Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.
• [11] 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.
• [12] Curcumin ameliorates high glucose-induced acute vascular endothelial dysfunction in rat thoracic aorta. Clin Exp Pharmacol Physiol. 2009 Dec;36(12):1177-82.
• [13] 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.