General Information of Drug Combination (ID: DC5NOXV)

Drug Combination Name
PHA-739358 Mebendazole
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs PHA-739358   DMGYBZI Mebendazole   DMO14SG
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 4.44
Bliss Independence Score: 4.44
Loewe Additivity Score: 18.58
LHighest Single Agent (HSA) Score: 18.6

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of PHA-739358
Disease Entry ICD 11 Status REF
Prostate cancer 2C82.0 Phase 2 [2]
PHA-739358 Interacts with 4 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Aurora kinase B (AURKB) TT5LS6T AURKB_HUMAN Inhibitor [5]
Aurora B messenger RNA (AURKB mRNA) TT9RTBL AURKB_HUMAN Inhibitor [6]
Aurora kinase A (AURKA) TTPS3C0 AURKA_HUMAN Inhibitor [5]
Aurora kinase C (AURKC) TTLYXIT AURKC_HUMAN Inhibitor [6]
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PHA-739358 Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Decreases Response To Substance [7]
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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 [9]
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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 [10]
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Mebendazole Interacts with 43 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases Expression [11]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Increases Expression [12]
Proepiregulin (EREG) OTRM4NQY EREG_HUMAN Increases Expression [13]
L-lactate dehydrogenase A chain (LDHA) OTN7K4XB LDHA_HUMAN Decreases Expression [14]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Increases Expression [15]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Expression [16]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Expression [17]
Interleukin-1 alpha (IL1A) OTPSGILV IL1A_HUMAN Increases Expression [13]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [13]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Increases Expression [13]
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) OTBPMIMW G3P_HUMAN Decreases Expression [14]
Protein S100-A8 (S100A8) OTVMOB3F S10A8_HUMAN Increases Expression [18]
Protein S100-A9 (S100A9) OTOARHCS S10A9_HUMAN Increases Expression [18]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Expression [19]
Hepatocyte growth factor receptor (MET) OT7K55MU MET_HUMAN Increases Expression [13]
Interleukin-6 receptor subunit alpha (IL6R) OTCQL07Z IL6RA_HUMAN Increases Expression [8]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [17]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Increases Phosphorylation [20]
Microtubule-associated protein tau (MAPT) OTMTP2Z7 TAU_HUMAN Decreases Expression [21]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1) OTA675TJ GTR1_HUMAN Decreases Expression [14]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Expression [8]
Hexokinase-1 (HK1) OTMPHE8O HXK1_HUMAN Decreases Expression [14]
Bone morphogenetic protein 6 (BMP6) OT9WN536 BMP6_HUMAN Increases Expression [13]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [17]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [17]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Decreases Expression [19]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Increases Expression [13]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [14]
Mitogen-activated protein kinase 8 (MAPK8) OTEREYS5 MK08_HUMAN Increases Phosphorylation [17]
Mitogen-activated protein kinase 9 (MAPK9) OTCEVJ9E MK09_HUMAN Increases Phosphorylation [17]
Neurogenic locus notch homolog protein 1 (NOTCH1) OTI1WADQ NOTC1_HUMAN Decreases Expression [22]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [14]
Transforming protein RhoA (RHOA) OT6YOJ9N RHOA_HUMAN Decreases Expression [23]
Ras-related C3 botulinum toxin substrate 1 (RAC1) OTKRO61U RAC1_HUMAN Decreases Expression [23]
Focal adhesion kinase 1 (PTK2) OT3Q1JDY FAK1_HUMAN Decreases Expression [23]
Interleukin-24 (IL24) OT4VUWH1 IL24_HUMAN Increases Expression [13]
Transcription factor HES-1 (HES1) OT8P19W2 HES1_HUMAN Decreases Expression [22]
Advanced glycosylation end product-specific receptor (AGER) OTPY0IH7 RAGE_HUMAN Increases Expression [18]
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 [23]
Multidrug and toxin extrusion protein 1 (SLC47A1) OTZX0U5Q S47A1_HUMAN Decreases Expression [19]
NACHT, LRR and PYD domains-containing protein 3 (NLRP3) OTZM6MHU NLRP3_HUMAN Increases Expression [18]
Cystine/glutamate transporter (SLC7A11) OTKJ6PXW XCT_HUMAN Increases Expression [13]
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⏷ Show the Full List of 43 DOT(s)

References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 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: 7937).
3 Mebendazole FDA Label
4 Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313.
5 Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
6 Potent and selective Aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition. J Med Chem. 2005 Apr 21;48(8):3080-4.
7 Abcg2 overexpression represents a novel mechanism for acquired resistance to the multi-kinase inhibitor Danusertib in BCR-ABL-positive cells in vitro. PLoS One. 2011 Apr 26;6(4):e19164. doi: 10.1371/journal.pone.0019164.
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 Alveolar echinococcosis of the liver in an adult with human immunodeficiency virus type-1 infection. Infection. 2004 Oct;32(5):299-302.
11 Prediction of aryl hydrocarbon receptor-mediated enzyme induction of drugs and chemicals by mRNA quantification. Chem Res Toxicol. 1998 Dec;11(12):1447-52.
12 The effects of mebendazole on P4501A activity in rat hepatocytes and HepG2 cellsComparison with tiabendazole and omeprazole. J Pharm Pharmacol. 2003 Jun;55(6):773-81.
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 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.
15 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.
16 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.
17 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.
18 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.
19 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.
20 Mebendazole induces apoptosis via Bcl-2 inactivation in chemoresistant melanoma cells. Mol Cancer Res. 2008 Aug;6(8):1308-15. doi: 10.1158/1541-7786.MCR-07-2159. Epub 2008 Jul 30.
21 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.
22 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.
23 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.