Details of the Drug Combination

General Information of Drug Combination (ID: DCIHYRW)

• Drug Combination Name: Glibenclamide + Dapagliflozin
• Indication: Hypertension; Status: Phase 4 [1]
• Component Drugs:
  Glibenclamide (DM8JXPZ): Small molecular drug
  Dapagliflozin (DM28UJG): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Glibenclamide

Disease Entry	ICD 11	Status	REF
Diabetic complication	5A2Y	Approved	[2]
Non-insulin dependent diabetes	5A11	Approved	[3]
Stroke	8B20	Phase 3	[4]

Glibenclamide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
ATP-binding cassette transporter C8 (ABCC8)	TTP835K	ABCC8_HUMAN	Modulator	[8]

Glibenclamide Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[9]
Multidrug resistance-associated protein 3 (ABCC3)	DTQ3ZHF	MRP3_HUMAN	Substrate	[10]
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[11]

Glibenclamide Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[12]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[13]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[14]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[14]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[15]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[12]

Glibenclamide Interacts with 17 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[16]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Decreases Activity	[17]
Aldo-keto reductase family 1 member C2 (AKR1C2)	OTQ2XMO3	AK1C2_HUMAN	Decreases Activity	[17]
Aldo-keto reductase family 1 member C1 (AKR1C1)	OTQKR4CM	AK1C1_HUMAN	Decreases Activity	[17]
Transmembrane protease serine 2 (TMPRSS2)	OTN44YQ5	TMPS2_HUMAN	Increases Expression	[18]
Insulin (INS)	OTZ85PDU	INS_HUMAN	Increases Expression	[19]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[20]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[21]
Cystic fibrosis transmembrane conductance regulator (CFTR)	OT6B22QH	CFTR_HUMAN	Decreases Activity	[22]
Calpain-2 catalytic subunit (CAPN2)	OTIAPE5J	CAN2_HUMAN	Increases Expression	[21]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Decreases Activity	[23]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Expression	[21]
Lysozyme C (LYZ)	OTD7H0G6	LYSC_HUMAN	Decreases Secretion	[24]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[25]
ATP-sensitive inward rectifier potassium channel 8 (KCNJ8)	OTZ8G8FE	KCNJ8_HUMAN	Decreases Activity	[26]
Angiotensin-converting enzyme 2 (ACE2)	OTTRZGU7	ACE2_HUMAN	Decreases Expression	[18]
Glucose-6-phosphate 1-dehydrogenase (G6PD)	OT300SMK	G6PD_HUMAN	Increases ADR	[27]

Indication(s) of Dapagliflozin

Disease Entry	ICD 11	Status	REF
Non-insulin dependent diabetes	5A11	Approved	[5]
Type-2 diabetes	5A11	Approved	[6]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[7]

Dapagliflozin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Sodium/glucose cotransporter 2 (SGLT2)	TTLWPVF	SC5A2_HUMAN	Modulator	[28]

Dapagliflozin Interacts with 7 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[29]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[29]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Metabolism	[29]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[29]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[29]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[29]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Metabolism	[29]

Dapagliflozin Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Sodium/glucose cotransporter 2 (SLC5A2)	OT93UUDI	SC5A2_HUMAN	Decreases Activity	[30]

References

• [1] ClinicalTrials.gov (NCT03089333) Effects of SGLT2 Inhibitor on Hemodynamic Parameters in Resistant Hypertensive Subjects
• [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: 2414).
• [3] Spectroscopic interactions of non-insulin-dependent diabetes mellitus with levocetirizine. Pak J Pharm Sci. 2021 Jul;34(4(Supplementary)):1639-1644.
• [4] Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
• [5] Dapagliflozin FDA Label
• [6] 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: 4594).
• [7] Dapagliflozin in Respiratory Failure in Patients With COVID-19 (DARE-19)
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
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• [20] Chromatographic studies of changes in binding of sulfonylurea drugs to human serum albumin due to glycation and fatty acids. J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Nov 15;878(30):3193-7. doi: 10.1016/j.jchromb.2010.09.033. Epub 2010 Oct 23.
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• [22] Comparative pharmacology of the activity of wild-type and G551D mutated CFTR chloride channel: effect of the benzimidazolone derivative NS004. J Membr Biol. 2003 Jul 15;194(2):109-17. doi: 10.1007/s00232-003-2030-z.
• [23] Role of two adjacent cytoplasmic tyrosine residues in MRP1 (ABCC1) transport activity and sensitivity to sulfonylureas. Biochem Pharmacol. 2005 Feb 1;69(3):451-61. doi: 10.1016/j.bcp.2004.10.014. Epub 2004 Dec 16.
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• [26] The intermediate conductance Ca2+-activated K+ channel inhibitor TRAM-34 stimulates proliferation of breast cancer cells via activation of oestrogen receptors. Br J Pharmacol. 2010 Feb 1;159(3):650-8. doi: 10.1111/j.1476-5381.2009.00557.x. Epub 2009 Dec 24.
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• [28] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
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• [30] Discovery of novel N--D-xylosylindole derivatives as sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors for the management of hyperglycemia in diabetes. J Med Chem. 2011 Jan 13;54(1):166-78. doi: 10.1021/jm101072y. Epub 2010 Dec 3.