Details of the Drug Combination

General Information of Drug Combination (ID: DCFX5DT)

• Drug Combination Name: Labetalol + Furosemide
• Indication: Hypertension, Pregnancy-Induced; Status: Phase 4 [1]
• Component Drugs:
  Labetalol (DMK8U72): Small molecular drug
  Furosemide (DMMQ8ZG): 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 Furosemide

Disease Entry	ICD 11	Status	REF
Congestive heart failure	BD10	Approved	[4]
Edema	MG29	Approved	[5]
Renal hypoplasia	N.A.	Approved	[5]

Furosemide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Solute carrier family 12 member 1 (SLC12A1)	TTS087L	S12A1_HUMAN	Blocker	[21]

Furosemide Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[22]
Organic anion transporter 1 (SLC22A6)	DTQ23VB	S22A6_HUMAN	Substrate	[23]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[23]

Furosemide Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[24]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[25]

Furosemide Interacts with 15 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Thiopurine S-methyltransferase (TPMT)	OTFOX70W	TPMT_HUMAN	Decreases Activity	[26]
Carbonic anhydrase 2 (CA2)	OTJRMUAG	CAH2_HUMAN	Decreases Activity	[27]
Renin (REN)	OT52GZR2	RENI_HUMAN	Increases Activity	[28]
Angiotensinogen (AGT)	OTBZLYR3	ANGT_HUMAN	Increases Expression	[29]
Natriuretic peptides A (NPPA)	OTMQNTNX	ANF_HUMAN	Decreases Expression	[30]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Secretion	[31]
HLA class I histocompatibility antigen, B alpha chain (HLA-B)	OTNXFWY2	HLAB_HUMAN	Affects Expression	[32]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[33]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Secretion	[31]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Decreases Secretion	[31]
Solute carrier family 12 member 2 (SLC12A2)	OT3ZJ3LH	S12A2_HUMAN	Decreases Activity	[34]
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Increases Activity	[35]
ATP-binding cassette sub-family C member 4 (ABCC4)	OTO27PAL	MRP4_HUMAN	Increases Transport	[36]
Parathyroid hormone/parathyroid hormone-related peptide receptor (PTH1R)	OTQF5ZAK	PTH1R_HUMAN	Increases ADR	[12]
Lipoprotein lipase (LPL)	OTTW0267	LIPL_HUMAN	Increases ADR	[12]

References

• [1] ClinicalTrials.gov (NCT04343235) Postpartum Management of Gestational Hypertensive Disorders Using Furosemide
• [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: 7207).
• [3] Labetalol 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: 4839).
• [5] Furosemide FDA Label
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