Details of the Drug Combination

General Information of Drug Combination (ID: DCBB67T)

• Drug Combination Name: Praziquantel + Albendazole
• Indication: HIV Infections; Status: Phase 1 [1]
• Component Drugs:
  Praziquantel (DMOU1PK): Small molecular drug
  Albendazole (DMYZ57N): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Praziquantel

Disease Entry	ICD 11	Status	REF
Flatworm infection	1F70-1F86	Approved	[2]
Opisthorchiasis	N.A.	Approved	[3]
Schistosomiasis	1F86	Approved	[3]

Praziquantel Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Glutathione-dependent PGD synthase (HPGDS)	TTCYE56	HPGDS_HUMAN	Inhibitor	[5]

Praziquantel Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[6]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[7]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[8]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[8]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[7]
Cytochrome P450 3A43 (CYP3A43)	DEO1IE3	CP343_HUMAN	Metabolism	[8]

Praziquantel Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Interleukin-5 (IL5)	OTAFPSCO	IL5_HUMAN	Increases Expression	[9]
Transient receptor potential cation channel subfamily M member 8 (TRPM8)	OT7ACGYK	TRPM8_HUMAN	Decreases Response To Substance	[10]

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	[2]

Albendazole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin beta (TUBB)	TTYFKSZ	NOUNIPROTAC	Binder	[12]

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	[13]

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	[7]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[14]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[15]

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	[14]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Increases Expression	[14]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Secretion	[16]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Affects Activity	[17]
Interleukin-6 receptor subunit alpha (IL6R)	OTCQL07Z	IL6RA_HUMAN	Increases Expression	[11]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[11]
Microtubule-associated protein tau (MAPT)	OTMTP2Z7	TAU_HUMAN	Decreases Expression	[18]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[11]
HLA class II histocompatibility antigen, DM beta chain (HLA-DMB)	OT17HGXJ	DMB_HUMAN	Affects Expression	[19]
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Increases Activity	[20]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[21]

References

• [1] ClinicalTrials.gov (NCT00507221) Empiric Therapy of Helminth Co-infection to Reduce HIV-1 Disease Progression
• [2] Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40.
• [3] Praziquantel FDA Label
• [4] Albendazole FDA Label
• [5] X-ray structure of glutathione S-transferase from Schistosoma japonicum in a new crystal form reveals flexibility of the substrate-binding site. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 Mar 1;61(Pt 3):263-5.
• [6] Biotransformation of praziquantel by human cytochrome p450 3A4 (CYP 3A4). Acta Pol Pharm. 2006 Sep-Oct;63(5):381-5.
• [7] 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.
• [8] Rifampin markedly decreases plasma concentrations of praziquantel in healthy volunteers. Clin Pharmacol Ther. 2002 Nov;72(5):505-13.
• [9] Chemotherapy for schistosomiasis in Ugandan fishermen: treatment can cause a rapid increase in interleukin-5 levels in plasma but decreased levels of eosinophilia and worm-specific immunoglobulin E. Infect Immun. 2004 Jul;72(7):4023-30. doi: 10.1128/IAI.72.7.4023-4030.2004.
• [10] The anthelminthic drug praziquantel is a selective agonist of the sensory transient receptor potential melastatin type 8 channel. Toxicol Appl Pharmacol. 2017 Dec 1;336:55-65. doi: 10.1016/j.taap.2017.10.012. Epub 2017 Oct 18.
• [11] 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.
• [12] Flubendazole interferes with a wide spectrum of cell homeostatic mechanisms in Echinococcus granulosus protoscoleces. Parasitol Int. 2009 Sep;58(3):270-7.
• [13] The anthelminthic agent albendazole does not interact with p-glycoprotein. Drug Metab Dispos. 2002 Apr;30(4):365-9.
• [14] 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.
• [15] Danazol inhibits cytochrome P450 2J2 activity in a substrate-independent manner. Drug Metab Dispos. 2015 Aug;43(8):1250-3.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] 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.