Details of the Drug Combination

General Information of Drug Combination (ID: DCEKE15)

• Drug Combination Name: Tindamax + Triapine
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Tindamax (DM3OWT4): Small molecular drug
  Triapine (DM7XZY5): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 0.23
  Bliss Independence Score: 0.23
  Loewe Additivity Score: 0.93
  LHighest Single Agent (HSA) Score: 0.96

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	[7]
Nitroreductase (NTR)	DEAN5EW	NFSB_ENTCL	Metabolism	[8]

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	[9]

Indication(s) of Triapine

Disease Entry	ICD 11	Status	REF
Nerve injury	ND56.4	Phase 2	[6]

Triapine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Ribonucleoside-diphosphate reductase M2 (RRM2)	TTBWDI0	RIR2_HUMAN	Modulator	[6]

Triapine Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[11]
Thioredoxin-dependent peroxide reductase, mitochondrial (PRDX3)	OTLB2WEU	PRDX3_HUMAN	Increases Oxidation	[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] 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] PAN-811 inhibits oxidative stress-induced cell death of human Alzheimer's disease-derived and age-matched olfactory neuroepithelial cells via suppression of intracellular reactive oxygen species. J Alzheimers Dis. 2009;17(3):611-9.
• [7] FDA label of Tinidazole. The 2020 official website of the U.S. Food and Drug Administration.
• [8] Overexpression, isotopic labeling, and spectral characterization of Enterobacter cloacae nitroreductase. Protein Expr Purif. 1998 Jun;13(1):53-60.
• [9] Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.
• [10] The iron-chelating drug triapine causes pronounced mitochondrial thiol redox stress. Toxicol Lett. 2011 Mar 5;201(2):130-6. doi: 10.1016/j.toxlet.2010.12.017. Epub 2010 Dec 31.
• [11] Distinct mechanisms of cell-kill by triapine and its terminally dimethylated derivative Dp44mT due to a loss or gain of activity of their copper(II) complexes. Biochem Pharmacol. 2014 Oct 1;91(3):312-22. doi: 10.1016/j.bcp.2014.08.006. Epub 2014 Aug 15.