Details of the Drug Combination

General Information of Drug Combination (ID: DCOH9YM)

• Drug Combination Name: DZNep + Mebendazole
• Indication: Diffuse intrinsic pontine glioma; Status: Investigative [1]
• Component Drugs:
  DZNep (DM0JXBK): Small molecular drug
  Mebendazole (DMO14SG): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: DIPG25
  Zero Interaction Potency (ZIP) Score: 20.368
  Bliss Independence Score: 22.318
  Loewe Additivity Score: 6.157
  LHighest Single Agent (HSA) Score: 8.351

Molecular Interaction Atlas of This Drug Combination

Indication(s) of DZNep

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[2]

DZNep Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adenosylhomocysteinase (AHCY)	TTE2KUJ	SAHH_HUMAN	Inhibitor	[2]

DZNep Interacts with 18 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Huntingtin-interacting protein 1 (HIP1)	OT7AKCFQ	HIP1_HUMAN	Decreases Expression	[5]
Histone-lysine N-methyltransferase SUV39H1 (SUV39H1)	OTDTF5BU	SUV91_HUMAN	Increases Expression	[5]
Histone-lysine N-methyltransferase NSD2 (NSD2)	OTQ6SW4R	NSD2_HUMAN	Increases Degradation	[6]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)	OTA675TJ	GTR1_HUMAN	Decreases Expression	[6]
Cadherin-1 (CDH1)	OTFJMXPM	CADH1_HUMAN	Increases Expression	[7]
Coilin (COIL)	OTP4I4DL	COIL_HUMAN	Increases Expression	[5]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[5]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Increases Expression	[6]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[6]
Transcriptional protein SWT1 (SWT1)	OTY4AFM1	SWT1_HUMAN	Decreases Expression	[5]
Transmembrane protein 87A (TMEM87A)	OT8ATDVX	TM87A_HUMAN	Increases Expression	[5]
Dapper homolog 3 (DACT3)	OTSNQ55G	DACT3_HUMAN	Affects Expression	[8]
Fructose-2,6-bisphosphatase TIGAR (TIGAR)	OTR7NMRJ	TIGAR_HUMAN	Decreases Expression	[6]
E3 ubiquitin-protein ligase Jade-2 (JADE2)	OTVG2MYF	JADE2_HUMAN	Increases Expression	[5]
Kelch-like protein 42 (KLHL42)	OTK6WARI	KLH42_HUMAN	Increases Expression	[5]
Two pore channel protein 1 (TPCN1)	OTT4C4DI	TPC1_HUMAN	Decreases Expression	[5]
DmX-like protein 1 (DMXL1)	OTWVL31L	DMXL1_HUMAN	Decreases Expression	[5]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Increases Response To Substance	[9]

Indication(s) of Mebendazole

Disease Entry	ICD 11	Status	REF
Ascariasis	1F62	Approved	[3]
Enterobiasis	1F65	Approved	[3]
Helminth infection	1F90.0	Approved	[3]
Trichuris trichiura infection	1F6G	Approved	[3]
Worm infection	1F90.Z	Approved	[4]

Mebendazole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin beta (TUBB)	TTYFKSZ	NOUNIPROTAC	Binder	[11]

Mebendazole Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[12]

Mebendazole Interacts with 23 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Proepiregulin (EREG)	OTRM4NQY	EREG_HUMAN	Increases Expression	[13]
Protein c-Fos (FOS)	OTJBUVWS	FOS_HUMAN	Increases Expression	[14]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[15]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Increases Expression	[13]
Protein S100-A8 (S100A8)	OTVMOB3F	S10A8_HUMAN	Increases Expression	[16]
Protein S100-A9 (S100A9)	OTOARHCS	S10A9_HUMAN	Increases Expression	[16]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Expression	[17]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Increases Expression	[13]
Interleukin-6 receptor subunit alpha (IL6R)	OTCQL07Z	IL6RA_HUMAN	Increases Expression	[10]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[18]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)	OTA675TJ	GTR1_HUMAN	Decreases Expression	[19]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[10]
Hexokinase-1 (HK1)	OTMPHE8O	HXK1_HUMAN	Decreases Expression	[19]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[18]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[18]
Mitogen-activated protein kinase 8 (MAPK8)	OTEREYS5	MK08_HUMAN	Increases Phosphorylation	[18]
Mitogen-activated protein kinase 9 (MAPK9)	OTCEVJ9E	MK09_HUMAN	Increases Phosphorylation	[18]
Neurogenic locus notch homolog protein 1 (NOTCH1)	OTI1WADQ	NOTC1_HUMAN	Decreases Expression	[20]
Transcription factor HES-1 (HES1)	OT8P19W2	HES1_HUMAN	Decreases Expression	[20]
PTB-containing, cubilin and LRP1-interacting protein (PID1)	OT5YJ7FI	PCLI1_HUMAN	Increases Expression	[13]
Rho guanine nucleotide exchange factor 2 (ARHGEF2)	OTBQTFRT	ARHG2_HUMAN	Decreases Expression	[21]
Multidrug and toxin extrusion protein 1 (SLC47A1)	OTZX0U5Q	S47A1_HUMAN	Decreases Expression	[17]
NACHT, LRR and PYD domains-containing protein 3 (NLRP3)	OTZM6MHU	NLRP3_HUMAN	Increases Expression	[16]

References

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• [3] Mebendazole FDA Label
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• [6] S-adenosylhomocysteine (AdoHcy)-dependent methyltransferase inhibitor DZNep overcomes breast cancer tamoxifen resistance via induction of NSD2 degradation and suppression of NSD2-driven redox homeostasis. Chem Biol Interact. 2020 Feb 1;317:108965. doi: 10.1016/j.cbi.2020.108965. Epub 2020 Jan 28.
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• [9] Disruption of the MYC-miRNA-EZH2 loop to suppress aggressive B-cell lymphoma survival and clonogenicity. Leukemia. 2013 Dec;27(12):2341-50. doi: 10.1038/leu.2013.94. Epub 2013 Mar 29.
• [10] 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.
• [11] Flubendazole interferes with a wide spectrum of cell homeostatic mechanisms in Echinococcus granulosus protoscoleces. Parasitol Int. 2009 Sep;58(3):270-7.
• [12] Alveolar echinococcosis of the liver in an adult with human immunodeficiency virus type-1 infection. Infection. 2004 Oct;32(5):299-302.
• [13] An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
• [14] Selection of drugs to test the specificity of the Tg.AC assay by screening for induction of the gadd153 promoter in vitro. Toxicol Sci. 2003 Aug;74(2):260-70. doi: 10.1093/toxsci/kfg113. Epub 2003 May 2.
• [15] Mebendazole induces apoptosis via C-MYC inactivation in malignant ascites cell line (AGP01). Toxicol In Vitro. 2019 Oct;60:305-312. doi: 10.1016/j.tiv.2019.06.010. Epub 2019 Jun 14.
• [16] Development of a cell-based assay system considering drug metabolism and immune- and inflammatory-related factors for the risk assessment of drug-induced liver injury. Toxicol Lett. 2014 Jul 3;228(1):13-24. doi: 10.1016/j.toxlet.2014.04.005. Epub 2014 Apr 15.
• [17] Mebendazole, an antiparasitic drug, inhibits drug transporters expression in preclinical model of gastric peritoneal carcinomatosis. Toxicol In Vitro. 2017 Sep;43:87-91. doi: 10.1016/j.tiv.2017.06.007. Epub 2017 Jun 9.
• [18] 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.
• [19] Mebendazole targets essential proteins in glucose metabolism leading gastric cancer cells to death. Toxicol Appl Pharmacol. 2023 Sep 15;475:116630. doi: 10.1016/j.taap.2023.116630. Epub 2023 Jul 18.
• [20] Mebendazole is a potent inhibitor to chemoresistant T cell acute lymphoblastic leukemia cells. Toxicol Appl Pharmacol. 2020 Jun 1;396:115001. doi: 10.1016/j.taap.2020.115001. Epub 2020 Apr 8.
• [21] Flubendazole and mebendazole impair migration and epithelial to mesenchymal transition in oral cell lines. Chem Biol Interact. 2018 Sep 25;293:124-132. doi: 10.1016/j.cbi.2018.07.026. Epub 2018 Jul 31.