General Information of Drug Combination (ID: DCTEVAT)

Drug Combination Name
Topiramate Piperaquine
Indication
Disease Entry Status REF
DD2 Investigative [1]
Component Drugs Topiramate   DM82Z30 Piperaquine   DMT70RC
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: DD2
Zero Interaction Potency (ZIP) Score: 2.837
Bliss Independence Score: 4.119
Loewe Additivity Score: 1.88
LHighest Single Agent (HSA) Score: 2.465

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Topiramate
Disease Entry ICD 11 Status REF
Alcohol dependence 6C40.2 Approved [2]
Epilepsy 8A60-8A68 Approved [2]
Epilepsy with generalized tonic-clonic seizures N.A. Approved [3]
Hyperlipidemia 5C80.Z Approved [3]
Hypertriglyceridemia 5C80.1 Approved [3]
Obesity 5B81 Approved [3]
Metabolic syndrome x 5C50-5D2Z Investigative [3]
Seizure disorder 8A6Z Investigative [4]
Topiramate Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Glutamate receptor ionotropic kainate 1 (GRIK1) TT0MYE2 GRIK1_HUMAN Antagonist [7]
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Topiramate Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [8]
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Topiramate Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [9]
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Topiramate Interacts with 12 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [9]
Glutamate receptor ionotropic, kainate 1 (GRIK1) OTO19X5C GRIK1_HUMAN Affects Response To Substance [10]
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Increases Activity [9]
Steroid 17-alpha-hydroxylase/17,20 lyase (CYP17A1) OTZKVLVJ CP17A_HUMAN Decreases Activity [11]
3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 (HSD3B2) OT02MSKN 3BHS2_HUMAN Decreases Activity [11]
Carbonic anhydrase 12 (CA12) OT6WNFU8 CAH12_HUMAN Decreases Activity [12]
Carbonic anhydrase 2 (CA2) OTJRMUAG CAH2_HUMAN Decreases Activity [12]
HLA class I histocompatibility antigen, A alpha chain (HLA-A) OTAH14LU HLAA_HUMAN Affects Expression [13]
HLA class II histocompatibility antigen, DM beta chain (HLA-DMB) OT17HGXJ DMB_HUMAN Affects Expression [13]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [14]
Pro-neuropeptide Y (NPY) OT4ICV3P NPY_HUMAN Increases ADR [15]
Galanin peptides (GAL) OTB3VPTO GALA_HUMAN Increases ADR [15]
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⏷ Show the Full List of 12 DOT(s)
Indication(s) of Piperaquine
Disease Entry ICD 11 Status REF
Malaria 1F40-1F45 Approved [5]
Piperaquine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Sarcoplasmic/endoplasmic reticulum calcium ATPase (ATP2A) TTZVSJ2 NOUNIPROTAC Inhibitor [5]
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Piperaquine Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [16]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [17]
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References

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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: 6849).
3 Topiramate FDA Label
4 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
5 The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
6 The association between the C802T polymorphism of the UDP-glucuronosyltransferase 2B7 gene and effective topiramate dosage. Zh Nevrol Psikhiatr Im S S Korsakova. 2007;107(5):63-4.
7 Development of medications for alcohol use disorders: recent advances and ongoing challenges. Expert Opin Emerg Drugs. 2005 May;10(2):323-43.
8 The antiepileptic drug topiramate is a substrate for human P-glycoprotein but not multidrug resistance proteins. Pharm Res. 2009 Nov;26(11):2464-70.
9 Dose-dependent induction of cytochrome P450 (CYP) 3A4 and activation of pregnane X receptor by topiramate. Epilepsia. 2003 Dec;44(12):1521-8.
10 A preliminary pharmacogenetic investigation of adverse events from topiramate in heavy drinkers. Exp Clin Psychopharmacol. 2009 Apr;17(2):122-9. doi: 10.1037/a0015700.
11 Effects of anticonvulsants on human p450c17 (17alpha-hydroxylase/17,20 lyase) and 3beta-hydroxysteroid dehydrogenase type 2. Epilepsia. 2005 Mar;46(3):444-8.
12 Design, synthesis, and biological evaluation of novel carbohydrate-based sulfamates as carbonic anhydrase inhibitors. J Med Chem. 2011 Mar 10;54(5):1481-9.
13 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.
14 Effects of the antiepileptic drugs lamotrigine, topiramate and gabapentin on hERG potassium currents. Epilepsy Res. 2005 Jan;63(1):17-25. doi: 10.1016/j.eplepsyres.2004.10.002. Epub 2004 Dec 8.
15 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.
16 Eurartesim - European Medicines Agency
17 Open-label crossover study of primaquine and dihydroartemisinin-piperaquine pharmacokinetics in healthy adult thai subjects. Antimicrob Agents Chemother. 2014 Dec;58(12):7340-6.