Details of the Drug Combination

General Information of Drug Combination (ID: DCCNH33)

• Drug Combination Name: Paromomycin + Sodium stibogluconate
• Indication: Visceral Leishmaniasis; Status: Phase 3 [1]
• Component Drugs:
  Paromomycin (DM1AGXN): Small molecular drug
  Sodium stibogluconate (DMH5MVE): N.A.

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 Sodium stibogluconate

Disease Entry	ICD 11	Status	REF
Advanced cancer	2A00-2F9Z	Approved	[4]
Leishmaniasis	1F54	Approved	[5]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[6]

Sodium stibogluconate Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Leishmania DNA topoisomerase I (Leishm TOP1)	TTNJKC3	Q9NJG8_LEIDO	Modulator	[6]

Sodium stibogluconate Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Decreases Expression	[9]
Interferon gamma receptor 1 (IFNGR1)	OTCTQBWW	INGR1_HUMAN	Increases Expression	[10]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A)	OT2D9DOV	TNR1A_HUMAN	Decreases Expression	[11]
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B)	OTDS2EAR	TNR1B_HUMAN	Decreases Expression	[11]
Tyrosine-protein phosphatase non-receptor type 6 (PTPN6)	OT33XNZM	PTN6_HUMAN	Decreases Activity	[12]

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] Perspectives of antimony compounds in oncology. Acta Pharmacol Sin. 2008 Aug;29(8):881-90.
• [5] Leishmaniasis in Norway. Tidsskr Nor Laegeforen. 2021 Feb 22;141(3).
• [6] Inhibition of Leishmania donovani promastigote DNA topoisomerase I and human monocyte DNA topoisomerases I and II by antimonial drugs and classical antitopoisomerase agents. J Parasitol. 2004 Oct;90(5):1155-62.
• [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] Evaluation of localized and systemic immune responses in cutaneous leishmaniasis caused by Leishmania tropica: interleukin-8, monocyte chemotactic protein-1 and nitric oxide are major regulatory factors. Immunology. 2010 Jun;130(2):193-201. doi: 10.1111/j.1365-2567.2009.03223.x. Epub 2010 Jan 22.
• [10] Antileishmanial drugs cause up-regulation of interferon-gamma receptor 1, not only in the monocytes of visceral leishmaniasis cases but also in cultured THP1 cells. Ann Trop Med Parasitol. 2003 Apr;97(3):245-57. doi: 10.1179/000349803235001714.
• [11] Soluble receptors for tumor necrosis factor as markers of disease activity in visceral leishmaniasis. J Infect Dis. 1995 Feb;171(2):498-501. doi: 10.1093/infdis/171.2.498.
• [12] Effects of sodium stibogluconate on differentiation and proliferation of human myeloid leukemia cell lines in vitro. Leukemia. 2002 Nov;16(11):2285-91. doi: 10.1038/sj.leu.2402692.