General Information of DFM (ID: F09089)
Name	Gemfibrozil 600 mg tablet
Company	Nivagen Pharmaceuticals
Active Pharmaceutical Ingredient (API)	Gemfibrozil		API Info click to show the detail info of this API
	Hypertriglyceridaemia		ICD-11: 5C80	Approved
Drug Inactive Ingredient (DIGs)
	DIG ID	DIG Info	DIG Name	DIG Functional Class
	E01VDF	DIG Info	Butyl alcohol	Flavoring agent ...
	E0F2PK	DIG Info	Calcium stearate	lubricant
	E03SQI	DIG Info	Carmellose sodium	Disintegrant
	E0IC9H	DIG Info	FD&C blue no. 1	Colorant
	E0N2PK	DIG Info	Isopropyl alcohol	Antimicrobial preservative ...
	E0PC2L	DIG Info	Polyethylene glycol 400	Coating agent ...
	E0R4JL	DIG Info	Polysorbate 80	Dispersing agent ...
	E0M1JK	DIG Info	Propylene glycol	Antimicrobial preservative ...
	E01UTV	DIG Info	Silicon dioxide	Anticaking agent ...
	E05BSD	DIG Info	Titanium dioxide	Coating agent ...

Full List of Biological Targets of DIG (DBTs) Regulated by DIG(s) in This DFM
G-protein coupled receptor (GPCR)
DBT Name: Serotonin receptor 2B (5HT2B)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	FD&C blue no. 1
Biological Activity	EC50 > 10 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	5HT2B_HUMAN
DBT Name: Adenosine receptor A3 (AA3R)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	IC50 = 9.3 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	AA3R_HUMAN
DBT Name: Cannabinoid CB2 receptor (CNR2)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	FD&C blue no. 1
Biological Activity	EC50 = 608.6 nM (estimated based on the structural similarity with CHEMBL2326294 )					[2]
Structural Similarity	Tanimoto coefficient = 0.805970149
Tested Species	Homo sapiens (Human)
UniProt ID	CNR2_HUMAN
DBT Name: Muscarinic receptor M1 (ACM1)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	IC50 = 2.6 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	ACM1_HUMAN
DBT Name: Muscarinic receptor M2 (ACM2)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	IC50 = 1.3 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	ACM2_HUMAN
DBT Name: Dopamine D3 receptor (DRD3)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	IC50 = 22 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	DRD3_HUMAN
DBT Name: Histamine H3 receptor (HRH3)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	IC50 = 5.3 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	HRH3_HUMAN
DBT Name: Thromboxane A2 receptor (TBXA2R)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	IC50 = 12 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	TA2R_HUMAN
Oxidoreductase (ORase)
DBT Name: Prostaglandin G/H synthase 1 (COX-1)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	IC50 = 1 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	PGH1_HUMAN
DBT Name: Prostaglandin G/H synthase 2 (COX-2)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment (1) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	FD&C blue no. 1
Biological Activity	IC50 = 22 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	PGH2_HUMAN
Experiment (2) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	IC50 = 2.9 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	PGH2_HUMAN
DBT Name: Cytochrome P450 3A (CYP3A)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment (1) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	Inhibition (tested by experiment)					[3]
Tested Species	Homo sapiens (Human)
UniProt ID	CP3A4_HUMAN ; CP3A5_HUMAN ; CP3A7_HUMAN ; CP343_HUMAN
Experiment (2) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	Protein expression downregulation (tested by experiment)					[4]
Tested Species	Homo sapiens (Human)
UniProt ID	CP3A4_HUMAN ; CP3A5_HUMAN ; CP3A7_HUMAN ; CP343_HUMAN
DBT Name: Albendazole monooxygenase (CYP3A4)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment (1) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Propylene glycol
Biological Activity	Inhibition ratio < 20 % (tested by experiment)					[5]
Tested Species	Homo sapiens (Human)
UniProt ID	CP3A4_HUMAN
Experiment (2) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Carmellose sodium
Biological Activity	Protein expression upregulation (tested by experiment)					[6]
Tested Species	Homo sapiens (Human)
UniProt ID	CP3A4_HUMAN
Experiment (3) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Carmellose sodium
Biological Activity	Protein expression upregulation (tested by experiment)					[6]
Tested Species	Homo sapiens (Human)
UniProt ID	CP3A4_HUMAN
Experiment (4) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polyethylene glycol 400
Biological Activity	IC50 = 10.77 mg.mL-1 (tested by experiment)					[5]
Tested Species	Homo sapiens (Human)
UniProt ID	CP3A4_HUMAN
Experiment (5) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	IC50 = 201 uM (tested by experiment)					[7]
Tested Species	Homo sapiens (Human)
UniProt ID	CP3A4_HUMAN
Experiment (6) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	IC50 = 400 uM (tested by experiment)					[8]
Tested Species	Homo sapiens (Human)
UniProt ID	CP3A4_HUMAN
Experiment (7) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	Protein expression downregulation (tested by experiment)					[6]
Tested Species	Homo sapiens (Human)
UniProt ID	CP3A4_HUMAN
Experiment (8) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Silicon dioxide
Biological Activity	Protein expression downregulation (tested by experiment)					[6]
Tested Species	Homo sapiens (Human)
UniProt ID	CP3A4_HUMAN
DBT Name: Cytochrome P450 2E1 (CYP2E1)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	IC50 = 225 uM (tested by experiment)					[7]
Tested Species	Homo sapiens (Human)
UniProt ID	CP2E1_HUMAN
DBT Name: Cytochrome P450 2C9 (CYP2C9)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment (1) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	EC50 = 374.2 uM (tested by experiment)					[7]
Tested Species	Homo sapiens (Human)
UniProt ID	CP2C9_HUMAN
Experiment (2) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	IC50 = 40 uM (tested by experiment)					[8]
Tested Species	Homo sapiens (Human)
UniProt ID	CP2C9_HUMAN
DBT Name: Mephenytoin 4-hydroxylase (CYP2C19)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	IC50 = 118.6 uM (tested by experiment)					[7]
Tested Species	Homo sapiens (Human)
UniProt ID	CP2CJ_HUMAN
DBT Name: Debrisoquine 4-hydroxylase (CYP2D6)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	EC50 = 486.4 uM (tested by experiment)					[7]
Tested Species	Homo sapiens (Human)
UniProt ID	CP2D6_HUMAN
DBT Name: Cytochrome P450 3A5 (CYP3A5)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	IC50 = 186.4 uM (tested by experiment)					[7]
Tested Species	Homo sapiens (Human)
UniProt ID	CP3A5_HUMAN
Hydrolase (HDase)
DBT Name: Acetylcholinesterase (ACHE)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	FD&C blue no. 1
Biological Activity	IC50 > 10 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	ACES_HUMAN
DBT Name: Phosphodiesterase 3A (PDE3A)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	IC50 > 3 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	PDE3A_HUMAN
DBT Name: Phosphodiesterase 4D (PDE4D)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment (1) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	FD&C blue no. 1
Biological Activity	IC50 = 28 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	PDE4D_HUMAN
Experiment (2) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	IC50 > 10 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	PDE4D_HUMAN
Primary active transporter (PAT)
DBT Name: Multidrug resistance protein 2 (ABCC2)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment (1) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polyethylene glycol 400
Biological Activity	Inhibition ratio = 67 % (tested by experiment)					[9]
Tested Species	Homo sapiens (Human)
UniProt ID	MRP2_HUMAN
Experiment (2) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polyethylene glycol 400
Biological Activity	Inhibition ratio > 73 % (tested by experiment)					[10]
Tested Species	Homo sapiens (Human)
UniProt ID	MRP2_HUMAN
DBT Name: Multidrug resistance protein 1 (ABCB1)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment (1) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polyethylene glycol 400
Biological Activity	Inhibition ratio = 28 % (tested by experiment)					[11]
Tested Species	Homo sapiens (Human)
UniProt ID	MDR1_HUMAN ; MDR3_HUMAN ; ABCB5_HUMAN
Experiment (2) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polyethylene glycol 400
Biological Activity	Inhibition ratio = 64 % (tested by experiment)					[12]
Tested Species	Homo sapiens (Human)
UniProt ID	MDR1_HUMAN ; MDR3_HUMAN ; ABCB5_HUMAN
Experiment (3) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	IC50 = 0.31 mg.mL-1 (tested by experiment)					[13]
Tested Species	Homo sapiens (Human)
UniProt ID	MDR1_HUMAN ; MDR3_HUMAN ; ABCB5_HUMAN
Experiment (4) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	Inhibition ratio = 60 % (tested by experiment)					[14]
Tested Species	Homo sapiens (Human)
UniProt ID	MDR1_HUMAN ; MDR3_HUMAN ; ABCB5_HUMAN
Experiment (5) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	Inhibition ratio > 250 % (tested by experiment)					[15]
Tested Species	Homo sapiens (Human)
UniProt ID	MDR1_HUMAN ; MDR3_HUMAN ; ABCB5_HUMAN
Potential-driven transporter (PDT)
DBT Name: Solute carrier SLCO2B1 (OATPB)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment (1) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	FD&C blue no. 1
Biological Activity	Inhibition ratio = 80.5 % (tested by experiment)					[16]
Tested Species	Homo sapiens (Human)
UniProt ID	SO2B1_HUMAN
Experiment (2) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	FD&C blue no. 1
Biological Activity	Ki = 13 uM (tested by experiment)					[16]
Tested Species	Homo sapiens (Human)
UniProt ID	SO2B1_HUMAN
DBT Name: Solute carrier SLCO1A2 (OATP-A)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment (1) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polyethylene glycol 400
Biological Activity	IC50 = 0.14 %(w/v) (tested by experiment)					[17]
Tested Species	Homo sapiens (Human)
UniProt ID	SO1A2_HUMAN
Experiment (2) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polyethylene glycol 400
Biological Activity	IC50 = 0.05 %(w/v) (tested by experiment)					[17]
Tested Species	Homo sapiens (Human)
UniProt ID	SO1A2_HUMAN
Nuclear receptor (NR)
DBT Name: Estrogen receptor alpha (ESR1)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	IC50 > 10 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	ESR1_HUMAN
DBT Name: Progesterone receptor (PGR)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	IC50 = 21 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	PRGR_HUMAN
Cell line (CELL)
DBT Name: Colon cancer Caco-2 cells (Caco-2)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 80
Biological Activity	Chylomicron secretion upregulation (tested by experiment)					[18]
Tested Species	Homo sapiens (Human)
DBT Name: Lymphoma P388/ADR cells (P388/ADR)				Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Isopropyl alcohol
Biological Activity	IC50 = 0.22 uM (estimated based on the structural similarity with CHEMBL545 )					[19]
Structural Similarity	Tanimoto coefficient = 0.789473684
Tested Species	Mus musculus (Mouse)
Cellosaurus ID	CVCL_IZ75

References
1	The activities of drug inactive ingredients on biological targets. Science. 2020 Jul 24;369(6502):403-413.
2	Novel triaryl sulfonamide derivatives as selective cannabinoid receptor 2 inverse agonists and osteoclast inhibitors: discovery, optimization, and biological evaluation. J Med Chem. 2013 Mar 14; 56(5):2045-58.
3	In vitro investigation on the impact of the surface-active excipients Cremophor EL, Tween 80 and Solutol HS 15 on the metabolism of midazolam. iopharm Drug Dispos. 2004 Jan;25(1):37-49.
4	Scientific perspectives on extending the provision for waivers of in vivo bioavailability and bioequivalence studies for drug products containing high solubility-low permeability drugs (BCS-Class 3). AAPS J. 2008 Jun;10(2):300-5.
5	Pharmaceutical excipients inhibit cytochrome P450 activity in cell free systems and after systemic administration. Eur J Pharm Biopharm. 2008 Sep;70(1):279-88.
6	Effects of commonly used excipients on the expression of CYP3A4 in colon and liver cells. Pharm Res. 2010 Aug;27(8):1703-12.
7	Mediation of in vitro cytochrome p450 activity by common pharmaceutical excipients. Mol Pharm. 2013 Jul 1;10(7):2739-48.
8	Effects of non-ionic surfactants on cytochrome P450-mediated metabolism in vitro. Eur J Pharm Biopharm. 2011 May;78(1):166-72.
9	Inhibition of human efflux transporter ABCC2 (MRP2) by self-emulsifying drug delivery system: influences of concentration and combination of excipients. J Pharm Pharm Sci. 2014;17(4):447-60.
10	Interactions between human multidrug resistance related protein (MRP2; ABCC2) and excipients commonly used in self-emulsifying drug delivery systems (SEDDS). Int J Pharm. 2013 Apr 15;447(1-2):192-8.
11	The effect of polyoxyethylene polymers on the transport of ranitidine in Caco-2 cell monolayers. Int J Pharm. 2011 May 16;409(1-2):164-8.
12	Modulation of intestinal P-glycoprotein function by polyethylene glycols and their derivatives by in vitro transport and in situ absorption studies. Int J Pharm. 2006 Apr 26;313(1-2):49-56.
13	Reversal of multidrug resistance by surfactants. Br J Cancer. 1992 Jul;66(1):62-8.
14	A comparison of commonly used polyethoxylated pharmaceutical excipients on their ability to inhibit P-glycoprotein activity in vitro. J Pharm Sci. 2002 Sep;91(9):1991-2002.
15	Effect of excipients on breast cancer resistance protein substrate uptake activity. J Control Release. 2007 Dec 4;124(1-2):1-5.
16	Bacterial metabolism rescues the inhibition of intestinal drug absorption by food and drug additives. Proc Natl Acad Sci U S A. 2020 Jul 7;117(27):16009-16018.
17	Pharmaceutical excipients influence the function of human uptake transporting proteins. Mol Pharm. 2012 Sep 4;9(9):2577-81.
18	Stimulation of triglyceride-rich lipoprotein secretion by polysorbate 80: in vitro and in vivo correlation using Caco-2 cells and a cannulated rat intestinal lymphatic model. Pharm Res. 2004 Dec;21(12):2320-6.
19	Synthesis and evaluation of dihydropyrroloquinolines that selectively antagonize P-glycoprotein. J Med Chem. 2004 Mar 11; 47(6):1413-22.

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