Details of the Drug Combination

General Information of Drug Combination (ID: DC0N038)

• Drug Combination Name: Vemurafenib + Digoxin
• Indication: Malignant Melanoma, Neoplasms; Status: Phase 1 [1]
• Component Drugs:
  Vemurafenib (DM62UG5): Small molecular drug
  Digoxin (DMQCTIH): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Vemurafenib

Disease Entry	ICD 11	Status	REF
Melanoma	2C30	Approved	[2]

Vemurafenib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Serine/threonine-protein kinase B-raf (BRAF)	TTWCGQT	BRAF_HUMAN	Modulator	[7]

Vemurafenib Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[8]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[9]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[9]

Vemurafenib 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]

Vemurafenib Interacts with 19 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Microphthalmia-associated transcription factor (MITF)	OT6XJCZH	MITF_HUMAN	Affects Expression	[5]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[11]
Cyclin-dependent kinase 4 (CDK4)	OT7EP05T	CDK4_HUMAN	Decreases Expression	[12]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[13]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[12]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[6]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[6]
CD70 antigen (CD70)	OTHB2AL1	CD70_HUMAN	Decreases Expression	[14]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Decreases Expression	[12]
Sterol regulatory element-binding protein 1 (SREBF1)	OTWBRPAI	SRBP1_HUMAN	Decreases Expression	[15]
Melanocyte protein PMEL (PMEL)	OTCDDHHM	PMEL_HUMAN	Increases Expression	[5]
Melanoma-associated antigen 1 (MAGEA1)	OTXAO193	MAGA1_HUMAN	Decreases Expression	[5]
Thyroxine 5-deiodinase (DIO3)	OTNTITOT	IOD3_HUMAN	Decreases Expression	[16]
Melanoma antigen recognized by T-cells 1 (MLANA)	OT1N2S2K	MAR1_HUMAN	Increases Expression	[5]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Expression	[13]
GTPase KRas (KRAS)	OT78QCN8	RASK_HUMAN	Affects Response To Substance	[17]
Serine/threonine-protein kinase B-raf (BRAF)	OT7S81XQ	BRAF_HUMAN	Increases Response To Substance	[18]
Heat shock 70 kDa protein 1A (HSPA1A)	OTKGIE76	HS71A_HUMAN	Decreases Response To Substance	[19]
GTPase NRas (NRAS)	OTVQ1DG3	RASN_HUMAN	Affects Response To Substance	[17]

Indication(s) of Digoxin

Disease Entry	ICD 11	Status	REF
Arrhythmia	BC9Z	Approved	[3]
Atrial fibrillation	BC81.3	Approved	[4]
Chronic heart failure	BD1Z	Approved	[4]
Congestive cardiac insufficiency	BD1Z	Approved	[3]
Heart failure	BD10-BD13	Approved	[3]

Digoxin Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Sodium/potassium-transporting ATPase (SPT ATPase)	TTQ38E9	AT1A1_HUMAN; AT1A2_HUMAN; AT1A3_HUMAN; AT1B1_HUMAN; AT1B2_HUMAN; AT1B3_HUMAN	Inhibitor	[21]
Organic anion transporter M1 (SLCO4C1)	TTACFNR	SO4C1_HUMAN	Modulator	[22]

Digoxin Interacts with 7 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[23]
Multidrug resistance protein 3 (ABCB4)	DTZRMK5	MDR3_HUMAN	Substrate	[24]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[25]
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[26]
Organic solute transporter subunit alpha (SLC51A)	DTMEQ32	OSTA_HUMAN	Substrate	[27]
Organic solute transporter subunit beta (SLC51B)	DT1V9AJ	OSTB_HUMAN	Substrate	[27]
Organic anion transporting polypeptide 4C1 (SLCO4C1)	DTY0QMU	SO4C1_HUMAN	Substrate	[28]

Digoxin Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[29]
Cardiac glycoside reductase 1 (cgr1)	DE84PFW	CGR1_EGGLE	Metabolism	[30]
Cardiac glycoside reductase 2 (cgr2)	DE9VSLW	CGR2_EGGLE	Metabolism	[30]

Digoxin Interacts with 15 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[31]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)	OTRT3F3U	HMDH_HUMAN	Increases ADR	[32]
Interleukin-6 receptor subunit alpha (IL6R)	OTCQL07Z	IL6RA_HUMAN	Decreases Expression	[20]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[33]
C-C motif chemokine 4 (CCL4)	OT6B8P25	CCL4_HUMAN	Decreases Expression	[20]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Decreases Expression	[20]
C-C motif chemokine 5 (CCL5)	OTSCA5CK	CCL5_HUMAN	Decreases Expression	[20]
Natriuretic peptides B (NPPB)	OTSN2IPY	ANFB_HUMAN	Increases Expression	[34]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[35]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Activity	[31]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Decreases Activity	[36]
Sodium/potassium-transporting ATPase subunit alpha-1 (ATP1A1)	OTCJ458Q	AT1A1_HUMAN	Increases ADR	[32]
p21 protein (HRAS)	OTFYE6AJ	P78460_HUMAN	Increases ADR	[32]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases ADR	[32]
Insulin (INS)	OTZ85PDU	INS_HUMAN	Decreases Response To Substance	[37]

References

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