Details of the Drug Combination

General Information of Drug Combination (ID: DCYNMAD)

• Drug Combination Name: Moxidectin + Albendazole
• Indication: Onchocerciasis; Status: Phase 3 [1]
• Component Drugs:
  Moxidectin (DMYGHX5): N.A.
  Albendazole (DMYZ57N): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Moxidectin

Disease Entry	ICD 11	Status	REF
Onchocerciasis	1F6A	Approved	[2]
River blindness	1F6A.0	Approved	[3]

Moxidectin Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Onchocerca Glutamate-gated chloride channel (Onchoc GluCl)	TTSNVHO	Q25634_ONCVO	Modulator	[3]
Gamma-aminobutyric acid receptor (GAR)	TTNJYV2	NOUNIPROTAC	Modulator	[3]

Moxidectin Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Expression	[6]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Increases Export	[7]

Indication(s) of Albendazole

Disease Entry	ICD 11	Status	REF
Echinococcus granulosus infectious disease	N.A.	Approved	[4]
Helminth infection	1F90.0	Approved	[4]
Worm infection	1F90.Z	Approved	[5]

Albendazole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin beta (TUBB)	TTYFKSZ	NOUNIPROTAC	Binder	[9]

Albendazole Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[10]

Albendazole Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[11]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[12]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[13]

Albendazole Interacts with 11 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Increases Expression	[12]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Increases Expression	[12]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Secretion	[14]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Affects Activity	[15]
Interleukin-6 receptor subunit alpha (IL6R)	OTCQL07Z	IL6RA_HUMAN	Increases Expression	[8]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[8]
Microtubule-associated protein tau (MAPT)	OTMTP2Z7	TAU_HUMAN	Decreases Expression	[16]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[8]
HLA class II histocompatibility antigen, DM beta chain (HLA-DMB)	OT17HGXJ	DMB_HUMAN	Affects Expression	[17]
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Increases Activity	[18]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[19]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Lymphatic Filariasis	DCDFVQA	N. A.	Phase 3	[20]

References

• [1] ClinicalTrials.gov (NCT04311671) Safety of a Single Dose of Moxidectin Compared With Ivermectin in Individuals Living in Onchocerciasis Endemic Areas and in Individuals Living in Onchocerciasis Endemic Areas With High Levels of Lymphatic Filariasis Co-endemicity Receiving Concomitant Albendazole
• [2] FDA Approved Drug Products from FDA Official Website. 2018. Application Number: (ANDA) 210867.
• [3] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [4] Albendazole FDA Label
• [5] Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40.
• [6] Reversal effects of two new milbemycin compounds on multidrug resistance in MCF-7/adr cells in vitro. Eur J Pharmacol. 2011 Jun 1;659(2-3):108-13. doi: 10.1016/j.ejphar.2011.03.023. Epub 2011 Mar 31.
• [7] In vitro and in vivo interaction of moxidectin with BCRP/ABCG2. Chem Biol Interact. 2009 Jun 15;180(1):106-12. doi: 10.1016/j.cbi.2009.02.009. Epub 2009 Feb 23.
• [8] Cell-based and cytokine-directed chemical screen to identify potential anti-multiple myeloma agents. Leuk Res. 2010 Jul;34(7):917-24. doi: 10.1016/j.leukres.2009.12.002. Epub 2010 Feb 8.
• [9] Flubendazole interferes with a wide spectrum of cell homeostatic mechanisms in Echinococcus granulosus protoscoleces. Parasitol Int. 2009 Sep;58(3):270-7.
• [10] The anthelminthic agent albendazole does not interact with p-glycoprotein. Drug Metab Dispos. 2002 Apr;30(4):365-9.
• [11] Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data. Eur J Clin Pharmacol. 2003 Sep;59(5-6):429-42.
• [12] Cytochrome P450 1A1/2 induction by antiparasitic drugs: dose-dependent increase in ethoxyresorufin O-deethylase activity and mRNA caused by quinine, primaquine and albendazole in HepG2 cells. Eur J Clin Pharmacol. 2002 Nov;58(8):537-42.
• [13] Danazol inhibits cytochrome P450 2J2 activity in a substrate-independent manner. Drug Metab Dispos. 2015 Aug;43(8):1250-3.
• [14] Stimulation of pro-inflammatory responses by mebendazole in human monocytic THP-1 cells through an ERK signaling pathway. Arch Toxicol. 2011 Mar;85(3):199-207. doi: 10.1007/s00204-010-0584-y. Epub 2010 Sep 17.
• [15] Identification of environmental chemicals that activate p53 signaling after in vitro metabolic activation. Arch Toxicol. 2022 Jul;96(7):1975-1987. doi: 10.1007/s00204-022-03291-5. Epub 2022 Apr 18.
• [16] Pharmacologic reductions of total tau levels; implications for the role of microtubule dynamics in regulating tau expression. Mol Neurodegener. 2006 Jul 26;1:6. doi: 10.1186/1750-1326-1-6.
• [17] Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
• [18] A Gene Expression Biomarker Predicts Heat Shock Factor 1 Activation in a Gene Expression Compendium. Chem Res Toxicol. 2021 Jul 19;34(7):1721-1737. doi: 10.1021/acs.chemrestox.0c00510. Epub 2021 Jun 25.
• [19] Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
• [20] ClinicalTrials.gov (NCT04410406) Moxidectin for LF, Cote d'Ivoire (DOLF)