Details of the Drug Combination

General Information of Drug Combination (ID: DC3NG06)

• Drug Combination Name: Aliskiren + Atenolol
• Indication: Marfan Syndrome; Status: Phase 1 [1]
• Component Drugs:
  Aliskiren (DM1BV7W): Small molecular drug
  Atenolol (DMNKG1Z): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Aliskiren

Disease Entry	ICD 11	Status	REF
Hypertension	BA00-BA04	Approved	[2]

Aliskiren Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Angiotensinogenase renin (REN)	TTB2MXP	RENI_HUMAN	Inhibitor	[5]

Aliskiren Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[6]
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[7]

Aliskiren Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]

Aliskiren Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Activity	[9]

Indication(s) of Atenolol

Disease Entry	ICD 11	Status	REF
Angina pectoris	BA40	Approved	[3]
Hypertension	BA00-BA04	Approved	[4]
Malignant essential hypertension	BA00	Approved	[3]
Myocardial infarction	BA41-BA43	Approved	[3]

Atenolol Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adrenergic receptor beta-1 (ADRB1)	TTR6W5O	ADRB1_HUMAN	Antagonist	[11]

Atenolol Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[12]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[13]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[14]

Atenolol Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[15]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[16]

Atenolol Interacts with 27 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Increases ADR	[17]
Potassium voltage-gated channel subfamily KQT member 1 (KCNQ1)	OT8SPJNX	KCNQ1_HUMAN	Affects Response To Substance	[18]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[19]
Renin (REN)	OT52GZR2	RENI_HUMAN	Decreases Activity	[20]
Angiotensinogen (AGT)	OTBZLYR3	ANGT_HUMAN	Decreases Expression	[21]
Natriuretic peptides A (NPPA)	OTMQNTNX	ANF_HUMAN	Decreases Expression	[22]
Apolipoprotein A-I (APOA1)	OT5THARI	APOA1_HUMAN	Decreases Expression	[23]
Apolipoprotein A-II (APOA2)	OTQ3HGTC	APOA2_HUMAN	Decreases Expression	[23]
Apolipoprotein B-100 (APOB)	OTH0UOCZ	APOB_HUMAN	Increases Expression	[23]
Beta-2 adrenergic receptor (ADRB2)	OTSDOX4Q	ADRB2_HUMAN	Increases Expression	[24]
Natriuretic peptides B (NPPB)	OTSN2IPY	ANFB_HUMAN	Increases Expression	[25]
Reduced folate transporter (SLC19A1)	OTWB0BTO	S19A1_HUMAN	Decreases Expression	[26]
Sodium- and chloride-dependent creatine transporter 1 (SLC6A8)	OT88C8JA	SC6A8_HUMAN	Decreases Expression	[10]
Beta-2-microglobulin (B2M)	OTDWN6NX	B2MG_HUMAN	Decreases Expression	[27]
Small nuclear ribonucleoprotein-associated protein N (SNRPN)	OTQB1ID1	RSMN_HUMAN	Increases Expression	[10]
Peptidyl-prolyl cis-trans isomerase FKBP5 (FKBP5)	OT404F9K	FKBP5_HUMAN	Decreases Expression	[10]
Solute carrier organic anion transporter family member 4C1 (SLCO4C1)	OTVILUUN	SO4C1_HUMAN	Increases Expression	[10]
C-type lectin domain family 2 member B (CLEC2B)	OT0W0M0L	CLC2B_HUMAN	Increases Expression	[10]
Ryanodine receptor 2 (RYR2)	OT0PF19E	RYR2_HUMAN	Increases Activity	[28]
Inward rectifier potassium channel 2 (KCNJ2)	OT2OQEZS	KCNJ2_HUMAN	Affects Response To Substance	[18]
Voltage-dependent L-type calcium channel subunit alpha-1C (CACNA1C)	OT6KFNMS	CAC1C_HUMAN	Increases Response To Substance	[29]
Sodium channel protein type 5 subunit alpha (SCN5A)	OTGYZWR6	SCN5A_HUMAN	Increases ADR	[17]
B2 bradykinin receptor (BDKRB2)	OTOA9D3W	BKRB2_HUMAN	Affects Response To Substance	[30]
Endothelin-1 (EDN1)	OTZCACEG	EDN1_HUMAN	Affects Response To Substance	[31]
Alpha-2A adrenergic receptor (ADRA2A)	OTZFGOTP	ADA2A_HUMAN	Affects Response To Substance	[32]
Potassium voltage-gated channel subfamily E member 1 (KCNE1)	OTZNQUW9	KCNE1_HUMAN	Increases ADR	[17]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Increases ADR	[17]

References

• [1] ClinicalTrials.gov (NCT01715207) Comparison of Aliskiren vs Negative Controls on Aortic Stiffness in Patients With MFS
• [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: 4812).
• [3] Atenolol FDA Label
• [4] 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: 548).
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• [31] Gender-specific association between preproendothelin-1 genotype and reduction of systolic blood pressure during antihypertensive treatment--results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA). Clin Cardiol. 2004 May;27(5):287-90. doi: 10.1002/clc.4960270510.
• [32] Single nucleotide polymorphisms predict the change in left ventricular mass in response to antihypertensive treatment. J Hypertens. 2004 Dec;22(12):2321-8. doi: 10.1097/00004872-200412000-00014.