Details of the Drug Combination

General Information of Drug Combination (ID: DCG5YN6)

• Drug Combination Name: Paromomycin + Miltefosine
• Indication: Visceral Leishmaniasis; Status: Phase 3 [1]
• Component Drugs:
  Paromomycin (DM1AGXN): Small molecular drug
  Miltefosine (DMND304): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Paromomycin

Disease Entry	ICD 11	Status	REF
Amoebiasis	1A36	Approved	[2]
Hepatic coma	N.A.	Approved	[2]
Intestinal amebiasis	1A36	Approved	[3]

Paromomycin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Staphylococcus 30S ribosomal subunit (Stap-coc pbp2)	TTQ8KVI	F4NA87_STAAU	Binder	[7]

Paromomycin Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Serine-protein kinase ATM (ATM)	OTQVOHLT	ATM_HUMAN	Increases Expression	[8]

Indication(s) of Miltefosine

Disease Entry	ICD 11	Status	REF
Chronic urticaria	N.A.	Approved	[4]
Leishmaniasis	1F54	Approved	[5]
Visceral leishmaniasis	1F54.0	Phase 2	[6]

Miltefosine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Phospholipase A2 (PLA2G1B)	TT9V5JH	PA21B_HUMAN	Inhibitor	[6]

Miltefosine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Choline phosphatase 1 (PLD1)	DEB2ZMT	PLD1_HUMAN	Metabolism	[9]

Miltefosine Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Protein kinase C alpha type (PRKCA)	OT5UWNRD	KPCA_HUMAN	Decreases Phosphorylation	[10]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Response To Substance	[11]

References

• [1] ClinicalTrials.gov (NCT03129646) Miltefosine/Paromomycin Phase III Trial for Treatment of Primary Visceral Leishmaniasis (VL) Patients in Eastern Africa
• [2] Paromomycin FDA Label
• [3] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 064171.
• [4] Miltefosine FDA Label
• [5] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [6] Novel antifungal agents, targets or therapeutic strategies for the treatment of invasive fungal diseases: a review of the literature (2005-2009). Rev Iberoam Micol. 2009 Mar 31;26(1):15-22.
• [7] Aminoglycoside association pathways with the 30S ribosomal subunit. J Phys Chem B. 2009 May 21;113(20):7322-30.
• [8] Correction of ATM gene function by aminoglycoside-induced read-through of premature termination codons. Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15676-81. doi: 10.1073/pnas.0405155101. Epub 2004 Oct 21.
• [9] Development of miltefosine as an oral treatment for leishmaniasis. Trans R Soc Trop Med Hyg. 2006 Dec;100 Suppl 1:S17-20.
• [10] Dimethylsphingosine and miltefosine induce apoptosis in lung adenocarcinoma A549?cells in a synergistic manner. Chem Biol Interact. 2019 Sep 1;310:108731. doi: 10.1016/j.cbi.2019.108731. Epub 2019 Jun 29.
• [11] MDR1 causes resistance to the antitumour drug miltefosine. Br J Cancer. 2001 May 18;84(10):1405-11. doi: 10.1054/bjoc.2001.1776.