Details of the Drug Combination

General Information of Drug Combination (ID: DCAAKLZ)

Drug Combination Name
Furazolidone Primidone
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Furazolidone   DM3P6V7 Primidone   DM0WX6I
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: 16.47
Bliss Independence Score: 16.47
Loewe Additivity Score: 30.65
LHighest Single Agent (HSA) Score: 30.65

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Furazolidone
Disease Entry ICD 11 Status REF
Diarrhea ME05.1 Approved [2]
Furazolidone Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Bacterial Deoxyribonucleic acid (Bact DNA) TTS1W4A NOUNIPROTAC Modulator [5]
------------------------------------------------------------------------------------
Furazolidone Interacts with 8 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Serine/threonine-protein kinase Chk1 (CHEK1) OTTTI622 CHK1_HUMAN Increases Expression [6]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [7]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A) OTDRV63V GA45A_HUMAN Increases Expression [8]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [6]
G1/S-specific cyclin-D3 (CCND3) OTNKPQ22 CCND3_HUMAN Increases Expression [9]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [6]
Breast cancer type 1 susceptibility protein (BRCA1) OT5BN6VH BRCA1_HUMAN Increases Expression [6]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [7]
------------------------------------------------------------------------------------
⏷ Show the Full List of 8 DOT(s)
Indication(s) of Primidone
Disease Entry ICD 11 Status REF
Epilepsy 8A60-8A68 Approved [3]
Epilepsy with generalized tonic-clonic seizures N.A. Approved [4]
Focal epilepsy N.A. Approved [4]
Primidone Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
GABA(A) receptor alpha-1 (GABRA1) TT1MPAY GBRA1_HUMAN Antagonist [10]
------------------------------------------------------------------------------------
Primidone Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [11]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [12]
------------------------------------------------------------------------------------
Primidone Interacts with 5 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [13]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Decreases Expression [14]
Protein S100-A8 (S100A8) OTVMOB3F S10A8_HUMAN Increases Expression [15]
Protein S100-A9 (S100A9) OTOARHCS S10A9_HUMAN Increases Expression [15]
Glutathione hydrolase 7 (GGT7) OTW4IO3I GGT7_HUMAN Increases ADR [16]
------------------------------------------------------------------------------------

References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
2 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 011270.
3 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: 5338).
4 Primidone FDA Label
5 Interaction of furazolidone with DNA. Biochim Biophys Acta. 1975 Aug 21;402(2):161-5.
6 Involvement of the activation of Nrf2/HO-1, p38 MAPK signaling pathways and endoplasmic reticulum stress in furazolidone induced cytotoxicity and S phase arrest in human hepatocyte L02 cells: modulation of curcumin. Toxicol Mech Methods. 2017 Mar;27(3):165-172. doi: 10.1080/15376516.2016.1273424. Epub 2017 Jan 8.
7 P21(Waf1/Cip1) plays a critical role in furazolidone-induced apoptosis in HepG2 cells through influencing the caspase-3 activation and ROS generation. Food Chem Toxicol. 2016 Feb;88:1-12. doi: 10.1016/j.fct.2015.12.004. Epub 2015 Dec 11.
8 The Effect of GADD45a on Furazolidone-Induced S-Phase Cell-Cycle Arrest in Human Hepatoma G2 Cells. J Biochem Mol Toxicol. 2015 Oct;29(10):489-495. doi: 10.1002/jbt.21719. Epub 2015 Jun 11.
9 Involvement of the p38 MAPK signaling pathway in S-phase cell-cycle arrest induced by Furazolidone in human hepatoma G2 cells. J Appl Toxicol. 2013 Dec;33(12):1500-5. doi: 10.1002/jat.2829. Epub 2012 Oct 30.
10 DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
11 Prescribrt's digital referenve - Primidone - Drug Summary.
12 Clinically significant pharmacokinetic drug interactions between antiepileptic drugs. J Clin Pharm Ther. 1999 Apr;24(2):87-92.
13 Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.
14 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.
15 Prediction of drug-induced liver injury using keratinocytes. J Appl Toxicol. 2017 Jul;37(7):863-872. doi: 10.1002/jat.3435. Epub 2017 Jan 31.
16 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.