Details of the Drug Combination

General Information of Drug Combination (ID: DC8BXG5)

• Drug Combination Name: Phenytoin + Eslicarbazepine acetate
• Indication: Epilepsy; Status: Phase 1 [1]
• Component Drugs:
  Phenytoin (DMNOKBV): Small molecular drug
  Eslicarbazepine acetate (DMREUZV): N.A.

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Phenytoin

Disease Entry	ICD 11	Status	REF
Epilepsy	8A60-8A68	Approved	[2]
Epilepsy with generalized tonic-clonic seizures	N.A.	Approved	[3]
Focal epilepsy	N.A.	Approved	[3]
Primary motor cortex epilepsy	N.A.	Approved	[3]

Phenytoin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Sodium channel unspecific (NaC)	TTRK8B9	NOUNIPROTAC	Blocker	[8]

Phenytoin Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[9]
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[10]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[11]

Phenytoin Interacts with 9 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[12]
Glutathione S-transferase alpha-1 (GSTA1)	DE4ZHS1	GSTA1_HUMAN	Metabolism	[13]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[14]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[14]
Cytochrome P450 2C18 (CYP2C18)	DEZMWRE	CP2CI_HUMAN	Metabolism	[15]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[15]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[16]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[14]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[15]

Phenytoin Interacts with 74 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Decreases Hydroxylation	[17]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Metabolism	[18]
HLA class I histocompatibility antigen, C alpha chain (HLA-C)	OTV38BUJ	HLAC_HUMAN	Increases ADR	[19]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Activity	[20]
Neurocan core protein (NCAN)	OT8OO6ZE	NCAN_HUMAN	Increases Expression	[6]
Plexin-B2 (PLXNB2)	OT56I2VD	PLXB2_HUMAN	Decreases Expression	[6]
Calpain-5 (CAPN5)	OTQ8QM7K	CAN5_HUMAN	Decreases Expression	[6]
Leucine-rich repeat transmembrane protein FLRT2 (FLRT2)	OTGD8TID	FLRT2_HUMAN	Increases Expression	[6]
Fibroblast growth factor receptor substrate 3 (FRS3)	OTTNP6H7	FRS3_HUMAN	Decreases Expression	[6]
Lathosterol oxidase (SC5D)	OT41KMW4	SC5D_HUMAN	Increases Expression	[6]
Eomesodermin homolog (EOMES)	OTB9VQFA	EOMES_HUMAN	Increases Expression	[6]
Metalloproteinase inhibitor 1 (TIMP1)	OTOXC51H	TIMP1_HUMAN	Increases Expression	[21]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Increases Expression	[22]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Decreases Expression	[23]
Interstitial collagenase (MMP1)	OTI4I2V1	MMP1_HUMAN	Decreases Expression	[24]
Creatine kinase M-type (CKM)	OTME0KO7	KCRM_HUMAN	Increases Expression	[25]
Collagen alpha-2(I) chain (COL1A2)	OTY7G382	CO1A2_HUMAN	Increases Expression	[6]
Chymotrypsin-like elastase family member 2A (CELA2A)	OTY8QG2J	CEL2A_HUMAN	Decreases Expression	[6]
Stromelysin-1 (MMP3)	OTGBI74Z	MMP3_HUMAN	Decreases Expression	[24]
Small ribosomal subunit protein uS2 (RPSA)	OTJZHEGT	RSSA_HUMAN	Increases Expression	[6]
Annexin A4 (ANXA4)	OTUCRYXL	ANXA4_HUMAN	Increases Expression	[6]
Homeobox protein Hox-B7 (HOXB7)	OTC7WYU8	HXB7_HUMAN	Increases Expression	[5]
Transforming growth factor beta-3 proprotein (TGFB3)	OT2LOUQ1	TGFB3_HUMAN	Increases Expression	[6]
Fibroblast growth factor 5 (FGF5)	OTQXGHBY	FGF5_HUMAN	Increases Expression	[6]
Collagen alpha-1(XI) chain (COL11A1)	OTB0DRMS	COBA1_HUMAN	Increases Expression	[6]
Collagen alpha-1(VI) chain (COL6A1)	OTYKSCOB	CO6A1_HUMAN	Decreases Expression	[6]
Collagen alpha-2(VI) chain (COL6A2)	OTQC6PPO	CO6A2_HUMAN	Increases Expression	[26]
Collagen alpha-3(VI) chain (COL6A3)	OTAS6R6I	CO6A3_HUMAN	Increases Expression	[26]
Interferon gamma receptor 1 (IFNGR1)	OTCTQBWW	INGR1_HUMAN	Increases Expression	[6]
Methylated-DNA--protein-cysteine methyltransferase (MGMT)	OT40A9WH	MGMT_HUMAN	Increases Methylation	[27]
Homeobox protein Hox-B9 (HOXB9)	OTMVHQOU	HXB9_HUMAN	Increases Expression	[5]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Increases Expression	[6]
Midkine (MDK)	OTF24HKC	MK_HUMAN	Increases Expression	[6]
Paired box protein Pax-3 (PAX3)	OTN5PJZV	PAX3_HUMAN	Decreases Expression	[5]
Paired box protein Pax-6 (PAX6)	OTOC9876	PAX6_HUMAN	Increases Expression	[5]
Protein S100-A4 (S100A4)	OTLRGFSQ	S10A4_HUMAN	Increases Expression	[6]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[24]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[24]
Fibroblast growth factor 9 (FGF9)	OT2SKDGM	FGF9_HUMAN	Increases Expression	[6]
Keratin, type II cytoskeletal 2 epidermal (KRT2)	OTG2EZEN	K22E_HUMAN	Increases Expression	[6]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Decreases Expression	[6]
Collagen alpha-1(XVIII) chain (COL18A1)	OTJFUH6O	COIA1_HUMAN	Decreases Expression	[6]
Large ribosomal subunit protein eL28 (RPL28)	OTEVRCBO	RL28_HUMAN	Increases Expression	[6]
Microtubule-associated protein 1B (MAP1B)	OTVXW089	MAP1B_HUMAN	Increases Expression	[6]
Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (PIP4K2A)	OTO9JO9U	PI42A_HUMAN	Increases Expression	[6]
Homeobox protein MOX-1 (MEOX1)	OTJEMT2D	MEOX1_HUMAN	Decreases Expression	[5]
Small ribosomal subunit protein mS29 (DAP3)	OTNPEZYM	RT29_HUMAN	Increases Expression	[6]
Protein S100-A10 (S100A10)	OTI71243	S10AA_HUMAN	Increases Expression	[6]
Disintegrin and metalloproteinase domain-containing protein 8 (ADAM8)	OT24S8YN	ADAM8_HUMAN	Decreases Expression	[6]
Transcription factor Sp3 (SP3)	OTYDQZ1T	SP3_HUMAN	Increases Expression	[6]
Fibromodulin (FMOD)	OT9EJ5H8	FMOD_HUMAN	Decreases Expression	[6]
Transcription factor 15 (TCF15)	OTA6UCWC	TCF15_HUMAN	Decreases Expression	[5]
Phosphatidate phosphatase LPIN1 (LPIN1)	OTQ75KF2	LPIN1_HUMAN	Increases Expression	[6]
Signal transducer and activator of transcription 4 (STAT4)	OTAK3VFR	STAT4_HUMAN	Decreases Expression	[6]
Nuclear receptor subfamily 1 group I member 3 (NR1I3)	OTS3SGH7	NR1I3_HUMAN	Increases Activity	[28]
Oligodendrocyte transcription factor 3 (OLIG3)	OTU8XLAF	OLIG3_HUMAN	Increases Expression	[5]
Sodium channel protein type 2 subunit alpha (SCN2A)	OTUSYE4Z	SCN2A_HUMAN	Decreases Activity	[29]
Eyes absent homolog 1 (EYA1)	OTHU807A	EYA1_HUMAN	Decreases Expression	[5]
Neurogenin-2 (NEUROG2)	OTAEMIGT	NGN2_HUMAN	Increases Expression	[5]
Sodium channel protein type 3 subunit alpha (SCN3A)	OT4C2LCB	SCN3A_HUMAN	Affects Binding	[30]
Death-associated protein kinase 2 (DAPK2)	OTWODUQG	DAPK2_HUMAN	Decreases Expression	[6]
Structural maintenance of chromosomes protein 3 (SMC3)	OTWGFRHD	SMC3_HUMAN	Increases Expression	[6]
Glutathione S-transferase kappa 1 (GSTK1)	OTDNGWAF	GSTK1_HUMAN	Decreases Expression	[6]
Adiponectin receptor protein 2 (ADIPOR2)	OT2HDTL8	PAQR2_HUMAN	Increases ADR	[7]
Protein kinase C-binding protein NELL1 (NELL1)	OTF3TX3N	NELL1_HUMAN	Increases ADR	[7]
Sodium channel subunit beta-1 (SCN1B)	OTGD78J3	SCN1B_HUMAN	Decreases Response To Substance	[30]
Bis(5'-adenosyl)-triphosphatase (FHIT)	OTGWBSLA	FHIT_HUMAN	Increases ADR	[7]
Sodium channel protein type 1 subunit alpha (SCN1A)	OTJ9ZTYI	SCN1A_HUMAN	Affects Response To Substance	[31]
Dachshund homolog 1 (DACH1)	OTMKNAGG	DACH1_HUMAN	Increases ADR	[7]
V-type proton ATPase subunit d 2 (ATP6V0D2)	OTMOZJO0	VA0D2_HUMAN	Increases ADR	[7]
A disintegrin and metalloproteinase with thrombospondin motifs 20 (ADAMTS20)	OTU0EKLN	ATS20_HUMAN	Increases ADR	[7]
Probable E3 ubiquitin-protein ligase IRF2BPL (IRF2BPL)	OTV8MNT1	I2BPL_HUMAN	Increases ADR	[7]
Glutathione hydrolase 7 (GGT7)	OTW4IO3I	GGT7_HUMAN	Increases ADR	[32]
cAMP-dependent protein kinase type II-beta regulatory subunit (PRKAR2B)	OTZEXEFH	KAP3_HUMAN	Increases ADR	[7]

Eslicarbazepine acetate Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[33]

References

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• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] Phenytoin FDA Label
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• [15] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
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