Details of the Drug Combination

General Information of Drug Combination (ID: DC49JTO)

• Drug Combination Name: Miltefosine + Pentoxifylline
• Indication: Leishmaniasis; Status: Phase 2 [1]
• Component Drugs:
  Miltefosine (DMND304): Small molecular drug
  Pentoxifylline (DMU3DNC): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Miltefosine

Disease Entry	ICD 11	Status	REF
Chronic urticaria	N.A.	Approved	[2]
Leishmaniasis	1F54	Approved	[3]
Visceral leishmaniasis	1F54.0	Phase 2	[4]

Miltefosine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Phospholipase A2 (PLA2G1B)	TT9V5JH	PA21B_HUMAN	Inhibitor	[4]

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	[7]

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	[8]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Response To Substance	[9]

Indication(s) of Pentoxifylline

Disease Entry	ICD 11	Status	REF
Alcoholic hepatitis	DB94.1	Approved	[5]
Intermittent claudication	BD40.00	Approved	[6]
Type-1 diabetes	5A10	Approved	[5]
Peripheral vascular disease	BD4Z	Investigative	[5]

Pentoxifylline Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tumor necrosis factor (TNF)	TTF8CQI	TNFA_HUMAN	.	[10]

Pentoxifylline Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[11]

Pentoxifylline Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Metalloproteinase inhibitor 1 (TIMP1)	OTOXC51H	TIMP1_HUMAN	Increases ADR	[12]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases ADR	[12]
Thrombomodulin (THBD)	OT8VHLKY	TRBM_HUMAN	Increases ADR	[12]
Matrix metalloproteinase-14 (MMP14)	OT9C197Z	MMP14_HUMAN	Increases ADR	[12]
Perforin-1 (PRF1)	OTFVXD7H	PERF_HUMAN	Increases ADR	[12]
Granzyme B (GZMB)	OTPPVIRS	GRAB_HUMAN	Increases ADR	[12]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Increases ADR	[12]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases ADR	[12]

References

• [1] ClinicalTrials.gov (NCT02530697) The Association of Miltefosine and Pentoxifylline to Treat Mucosal and Cutaneous Leishmaniasis: A Clinical Trial in Brazil
• [2] Miltefosine FDA Label
• [3] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [4] 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.
• [5] Pentoxifylline FDA Label
• [6] 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: 7095).
• [7] Development of miltefosine as an oral treatment for leishmaniasis. Trans R Soc Trop Med Hyg. 2006 Dec;100 Suppl 1:S17-20.
• [8] 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.
• [9] MDR1 causes resistance to the antitumour drug miltefosine. Br J Cancer. 2001 May 18;84(10):1405-11. doi: 10.1054/bjoc.2001.1776.
• [10] Targeted therapies in myelodysplastic syndromes: ASH 2003 review. Semin Hematol. 2004 Apr;41(2 Suppl 4):13-20.
• [11] Cytochrome P450 isozymes involved in lisofylline metabolism to pentoxifylline in human liver microsomes. Drug Metab Dispos. 1997 Dec;25(12):1354-8.
• [12] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.