Details of the Drug Combination

General Information of Drug Combination (ID: DC5BEWA)

• Drug Combination Name: Labetalol + Atenolol
• Indication: Systolic Hypertension; Status: Phase 1 [1]
• Component Drugs:
  Labetalol (DMK8U72): Small molecular drug
  Atenolol (DMNKG1Z): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Labetalol

Disease Entry	ICD 11	Status	REF
Hypertension	BA00-BA04	Approved	[2]
Hypertension, pregnancy-induced	N.A.	Approved	[3]
Malignant essential hypertension	BA00	Approved	[3]

Labetalol Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adrenergic receptor Alpha-1 (ADRA1)	TTG28O6	NOUNIPROTAC	Antagonist	[6]

Labetalol Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[8]

Labetalol Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[9]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[10]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[11]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[9]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Metabolism	[9]
UDP-glucuronosyltransferase 2B4 (UGT2B4)	DENUPDX	UD2B4_HUMAN	Metabolism	[9]

Labetalol Interacts with 9 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Increases ADR	[12]
Renin (REN)	OT52GZR2	RENI_HUMAN	Decreases Activity	[13]
Angiotensinogen (AGT)	OTBZLYR3	ANGT_HUMAN	Decreases Expression	[14]
Natriuretic peptides A (NPPA)	OTMQNTNX	ANF_HUMAN	Decreases Activity	[13]
Prolactin (PRL)	OTWFQGX7	PRL_HUMAN	Increases Expression	[15]
Beta-2 adrenergic receptor (ADRB2)	OTSDOX4Q	ADRB2_HUMAN	Decreases Activity	[16]
Beta-1 adrenergic receptor (ADRB1)	OTQBWN4U	ADRB1_HUMAN	Decreases Activity	[16]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Activity	[17]
Angiotensin-converting enzyme 2 (ACE2)	OTTRZGU7	ACE2_HUMAN	Increases Activity	[18]

Indication(s) of Atenolol

Disease Entry	ICD 11	Status	REF
Angina pectoris	BA40	Approved	[4]
Hypertension	BA00-BA04	Approved	[5]
Malignant essential hypertension	BA00	Approved	[4]
Myocardial infarction	BA41-BA43	Approved	[4]

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	[20]

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	[21]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[22]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[23]

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	[24]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[25]

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	[12]
Potassium voltage-gated channel subfamily KQT member 1 (KCNQ1)	OT8SPJNX	KCNQ1_HUMAN	Affects Response To Substance	[26]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[27]
Renin (REN)	OT52GZR2	RENI_HUMAN	Decreases Activity	[28]
Angiotensinogen (AGT)	OTBZLYR3	ANGT_HUMAN	Decreases Expression	[29]
Natriuretic peptides A (NPPA)	OTMQNTNX	ANF_HUMAN	Decreases Expression	[30]
Apolipoprotein A-I (APOA1)	OT5THARI	APOA1_HUMAN	Decreases Expression	[31]
Apolipoprotein A-II (APOA2)	OTQ3HGTC	APOA2_HUMAN	Decreases Expression	[31]
Apolipoprotein B-100 (APOB)	OTH0UOCZ	APOB_HUMAN	Increases Expression	[31]
Beta-2 adrenergic receptor (ADRB2)	OTSDOX4Q	ADRB2_HUMAN	Increases Expression	[32]
Natriuretic peptides B (NPPB)	OTSN2IPY	ANFB_HUMAN	Increases Expression	[33]
Reduced folate transporter (SLC19A1)	OTWB0BTO	S19A1_HUMAN	Decreases Expression	[34]
Sodium- and chloride-dependent creatine transporter 1 (SLC6A8)	OT88C8JA	SC6A8_HUMAN	Decreases Expression	[19]
Beta-2-microglobulin (B2M)	OTDWN6NX	B2MG_HUMAN	Decreases Expression	[35]
Small nuclear ribonucleoprotein-associated protein N (SNRPN)	OTQB1ID1	RSMN_HUMAN	Increases Expression	[19]
Peptidyl-prolyl cis-trans isomerase FKBP5 (FKBP5)	OT404F9K	FKBP5_HUMAN	Decreases Expression	[19]
Solute carrier organic anion transporter family member 4C1 (SLCO4C1)	OTVILUUN	SO4C1_HUMAN	Increases Expression	[19]
C-type lectin domain family 2 member B (CLEC2B)	OT0W0M0L	CLC2B_HUMAN	Increases Expression	[19]
Ryanodine receptor 2 (RYR2)	OT0PF19E	RYR2_HUMAN	Increases Activity	[36]
Inward rectifier potassium channel 2 (KCNJ2)	OT2OQEZS	KCNJ2_HUMAN	Affects Response To Substance	[26]
Voltage-dependent L-type calcium channel subunit alpha-1C (CACNA1C)	OT6KFNMS	CAC1C_HUMAN	Increases Response To Substance	[37]
Sodium channel protein type 5 subunit alpha (SCN5A)	OTGYZWR6	SCN5A_HUMAN	Increases ADR	[12]
B2 bradykinin receptor (BDKRB2)	OTOA9D3W	BKRB2_HUMAN	Affects Response To Substance	[38]
Endothelin-1 (EDN1)	OTZCACEG	EDN1_HUMAN	Affects Response To Substance	[39]
Alpha-2A adrenergic receptor (ADRA2A)	OTZFGOTP	ADA2A_HUMAN	Affects Response To Substance	[40]
Potassium voltage-gated channel subfamily E member 1 (KCNE1)	OTZNQUW9	KCNE1_HUMAN	Increases ADR	[12]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Increases ADR	[12]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Obesity, Morbid	DCFSHSV	N. A.	Phase 1	[41]

References

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• [3] Labetalol FDA Label
• [4] Atenolol FDA Label
• [5] 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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