Details of the Drug Combination

General Information of Drug Combination (ID: DCFN2J8)

• Drug Combination Name: Clopidogrel + Ramipril
• Indication: Diabetes Type 2; Status: Phase 1 [1]
• Component Drugs:
  Clopidogrel (DMOL54H): Small molecular drug
  Ramipril (DM2R68E): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Clopidogrel

Disease Entry	ICD 11	Status	REF
Acute coronary syndrome	BA41	Approved	[2]
Atherosclerosis	BD40	Approved	[2]
Myocardial infarction	BA41-BA43	Approved	[2]
Thrombosis	DB61-GB90	Approved	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[4]
Intracranial embolism	8B22.1	Investigative	[2]

Clopidogrel Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
P2Y purinoceptor 12 (P2RY12)	TTZ1DT0	P2Y12_HUMAN	Antagonist	[9]

Clopidogrel Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[10]

Clopidogrel Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[11]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[12]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[13]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[13]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[14]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[15]

Clopidogrel Interacts with 26 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[16]
Cytochrome P450 2B6 (CYP2B6)	OTOYO4S7	CP2B6_HUMAN	Increases Expression	[16]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Increases Oxidation	[17]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Affects Response To Substance	[18]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Expression	[10]
P2Y purinoceptor 12 (P2RY12)	OTX2W0WD	P2Y12_HUMAN	Affects Response To Substance	[19]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Increases ADR	[20]
Stearoyl-CoA desaturase (SCD)	OTB1073G	SCD_HUMAN	Decreases Expression	[16]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[21]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Activity	[22]
Thrombospondin-1 (THBS1)	OT0ECWK3	TSP1_HUMAN	Increases Expression	[21]
C-C motif chemokine 4 (CCL4)	OT6B8P25	CCL4_HUMAN	Increases Expression	[23]
C-C motif chemokine 5 (CCL5)	OTSCA5CK	CCL5_HUMAN	Increases Expression	[23]
Brain-derived neurotrophic factor (BDNF)	OTLGH7EW	BDNF_HUMAN	Decreases Secretion	[24]
Phosphoenolpyruvate carboxykinase, cytosolic (PCK1)	OTNWEJ5Y	PCKGC_HUMAN	Increases Expression	[16]
Glucose-6-phosphatase catalytic subunit 1 (G6PC1)	OTJ6FM9F	G6PC1_HUMAN	Decreases Expression	[16]
Tight junction protein ZO-1 (TJP1)	OTBDCUPK	ZO1_HUMAN	Decreases Expression	[25]
Nuclear receptor subfamily 1 group I member 3 (NR1I3)	OTS3SGH7	NR1I3_HUMAN	Affects Localization	[16]
Occludin (OCLN)	OTSUTVWL	OCLN_HUMAN	Decreases Expression	[25]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[22]
Thyroid hormone-inducible hepatic protein (THRSP)	OTKYE01L	THRSP_HUMAN	Increases Expression	[16]
Proteinase-activated receptor 1 (F2R)	OT4WVWBO	PAR1_HUMAN	Affects Response To Substance	[26]
Serum paraoxonase/arylesterase 1 (PON1)	OTD0Z2XO	PON1_HUMAN	Affects Response To Substance	[27]
Cytochrome P450 2C9 (CYP2C9)	OTGLBN29	CP2C9_HUMAN	Decreases Metabolism	[28]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases Response To Substance	[29]
Integrin beta-3 (ITGB3)	OTWCK1K6	ITB3_HUMAN	Decreases Response To Substance	[30]

Indication(s) of Ramipril

Disease Entry	ICD 11	Status	REF
Acute heart failure	BD10-BD13	Approved	[5]
Chronic heart failure	BD1Z	Approved	[6]
Congestive heart failure	BD10	Approved	[7]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[8]
Stroke	8B20	Investigative	[6]

Ramipril Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Angiotensin-converting enzyme (ACE)	TTL69WB	ACE_HUMAN	Inhibitor	[31]
HUMAN angiotensin-converting enzyme (ACE)	TTGFNPD	ACE_HUMAN	Inhibitor	[32]

Ramipril Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[33]
Peptide transporter 2 (SLC15A2)	DT8QKNP	S15A2_HUMAN	Substrate	[33]

Ramipril Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Renin (REN)	OT52GZR2	RENI_HUMAN	Increases Activity	[34]
Platelet-derived growth factor subunit B (PDGFB)	OTMFMFC3	PDGFB_HUMAN	Decreases Expression	[35]
Platelet-derived growth factor subunit A (PDGFA)	OTCMZ0W8	PDGFA_HUMAN	Decreases Expression	[35]
Leptin (LEP)	OT5Q7ODW	LEP_HUMAN	Decreases Expression	[36]
Adiponectin (ADIPOQ)	OTNX23LE	ADIPO_HUMAN	Decreases Expression	[37]
Liver carboxylesterase 1 (CES1)	OT9L0LR8	EST1_HUMAN	Increases Hydrolysis	[38]
Angiotensin-converting enzyme (ACE)	OTDF1964	ACE_HUMAN	Increases ADR	[39]
B2 bradykinin receptor (BDKRB2)	OTOA9D3W	BKRB2_HUMAN	Increases ADR	[40]

References

• [1] ClinicalTrials.gov (NCT01743014) Ramipril and Clopidogrel in Oxidative Stress, Vascular Inflammation and Endothelial Dysfunction in Type 2 Diabetes and Diabetic Nephropathy
• [2] Clopidogrel FDA Label
• [3] 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: 7150).
• [4] Preventing Cardiac Complication of COVID-19 Disease With Early Acute Coronary Syndrome Therapy: A Randomised Controlled Trial. (C-19-ACS)
• [5] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 202392.
• [6] Ramipril FDA Label
• [7] 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: 6339).
• [8] ClinicalTrials.gov (NCT04366050) Ramipril for the Treatment of COVID-19. U.S. National Institutes of Health.
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