Details of the Drug Combination

General Information of Drug Combination (ID: DCGVSG1)

Drug Combination Name
Mephenytoin Pizotyline
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Mephenytoin   DM5UGDK Pizotyline   DMV74ZH
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: 3.07
Bliss Independence Score: 3.07
Loewe Additivity Score: 17.24
LHighest Single Agent (HSA) Score: 17.24

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Mephenytoin
Disease Entry ICD 11 Status REF
Epilepsy 8A60-8A68 Approved [2]
Mephenytoin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Voltage-gated sodium channel alpha Nav1.5 (SCN5A) TTZOVE0 SCN5A_HUMAN Blocker [4]
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Mephenytoin Interacts with 9 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [5]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [6]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [7]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [5]
Cytochrome P450 2C18 (CYP2C18) DEZMWRE CP2CI_HUMAN Metabolism [8]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [9]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [8]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [10]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [11]
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⏷ Show the Full List of 9 DME(s)
Mephenytoin Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2B6 (CYP2B6) OTOYO4S7 CP2B6_HUMAN Decreases Methylation [12]
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Indication(s) of Pizotyline
Disease Entry ICD 11 Status REF
Headache 8A80-8A84 Approved [3]
Pizotyline Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
5-HT receptor (5HTR) TT85JO3 NOUNIPROTAC Modulator [13]
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Pizotyline Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
UDP-glucuronosyltransferase 2B10 (UGT2B10) DEI8NGH UDB10_HUMAN Metabolism [14]
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Pizotyline Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [15]
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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: 7223).
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: 93).
4 Lacosamide: a new approach to target voltage-gated sodium currents in epileptic disorders. CNS Drugs. 2009;23(7):555-68.
5 Species differences in stereoselective metabolism of mephenytoin by cytochrome P450 (CYP2C and CYP3A). J Pharmacol Exp Ther. 1993 Jan;264(1):89-94.
6 Comparison of (S)-mephenytoin and proguanil oxidation in vitro: contribution of several CYP isoforms. Br J Clin Pharmacol. 1999 Aug;48(2):158-67.
7 Ethnic differences in genetic polymorphisms of CYP2D6, CYP2C19, CYP3As and MDR1/ABCB1. Drug Metab Pharmacokinet. 2004 Apr;19(2):83-95.
8 Cytochrome P450 metabolic dealkylation of nine N-nitrosodialkylamines by human liver microsomes. Carcinogenesis. 1996 Sep;17(9):2029-34.
9 Evidence that CYP2C19 is the major (S)-mephenytoin 4'-hydroxylase in humans. Biochemistry. 1994 Feb 22;33(7):1743-52.
10 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
11 Cytochromes P450 mediating the N-demethylation of amitriptyline. Br J Clin Pharmacol. 1997 Feb;43(2):137-44.
12 Evaluation of cytochrome P450 probe substrates commonly used by the pharmaceutical industry to study in vitro drug interactions. Drug Metab Dispos. 2002 Dec;30(12):1311-9.
13 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
14 Human UDP-glucuronosyltransferase (UGT) 2B10 in drug N-glucuronidation: substrate screening and comparison with UGT1A3 and UGT1A4. Drug Metab Dispos. 2013 Jul;41(7):1389-97.
15 Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.