General Information of DFM (ID: F05454)
Name	Tolterodine 4 mg capsule
Company	Greenstone; Pharmacia and Upjohn Company
Active Pharmaceutical Ingredient (API)	Tolterodine		API Info click to show the detail info of this API
	Overactive bladder		ICD-11: GC50	Approved
Drug Inactive Ingredient (DIGs)
	DIG ID	DIG Info	DIG Name	DIG Functional Class
	E0L3MB	DIG Info	FD&C blue no. 2	Colorant
	E0X2OX	DIG Info	Medium-chain triglyceride	Emollient ...
	E0R0WE	DIG Info	Oleic acid	Emulsifying agent ...
	E0Q3PU	DIG Info	Saccharose	Binding agent ...

Full List of Biological Targets of DIG (DBTs) Regulated by DIG(s) in This DFM
G-protein coupled receptor (GPCR)
DBT Name: Adenosine receptor A3 (AA3R)				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	Oleic acid
Biological Activity	IC50 = 12 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	AA3R_HUMAN
Experiment (2) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	FD&C blue no. 2
Biological Activity	IC50 = 1 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	AA3R_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	Oleic acid
Biological Activity	IC50 = 13 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	ACM1_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	Oleic acid
Biological Activity	IC50 = 25 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	TA2R_HUMAN
Oxidoreductase (ORase)
DBT Name: Aromatase (ARO1)				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	Oleic acid
Biological Activity	IC50 = 32700 nM (tested by experiment)					[2]
Tested Species	Homo sapiens (Human)
UniProt ID	CP19A_HUMAN
DBT Name: Monoamine oxidase A (MAO-A)				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. 2
Biological Activity	IC50 > 3 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	AOFA_HUMAN
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 (1) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Oleic acid
Biological Activity	IC50 > 500000 nM (tested by experiment)					[3]
Tested Species	Bos taurus (Bovine)
UniProt ID	PGH1_BOVIN
Experiment (2) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Oleic acid
Biological Activity	IC50 = 6.7 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	Oleic acid
Biological Activity	IC50 > 500000 nM (tested by experiment)					[3]
Tested Species	Ovis aries (Sheep)
UniProt ID	PGH2_SHEEP
Experiment (2) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Oleic acid
Biological Activity	IC50 = 3.5 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	PGH2_HUMAN
Experiment (3) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	FD&C blue no. 2
Biological Activity	IC50 = 24 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	PGH2_HUMAN
DBT Name: Albendazole monooxygenase (CYP3A4)				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	Oleic acid
Biological Activity	Inhibition ratio < 20 % (tested by experiment)					[4]
Tested Species	Homo sapiens (Human)
UniProt ID	CP3A4_HUMAN
Transferase (TFase)
DBT Name: Telomerase reverse transcriptase (TERT)				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	Oleic acid
Biological Activity	IC50 = 8600 nM (tested by experiment)					[5]
Tested Species	Homo sapiens (Human)
UniProt ID	TERT_HUMAN
DBT Name: VEGF-2 receptor (KDR)				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. 2
Biological Activity	IC50 = 3.1 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	VGFR2_HUMAN
Hydrolase (HDase)
DBT Name: Proconvertin-TF complex (F7-F3)				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	Oleic acid
Biological Activity	IC50 = 80000 nM (tested by experiment)					[6]
Tested Species	Homo sapiens (Human)
UniProt ID	FA7_HUMAN ; TF_HUMAN
DBT Name: Protein-tyrosine phosphatase 1D (PTPN11)				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. 2
Biological Activity	IC50 = 7940 nM (estimated based on the structural similarity with CHEMBL3692077 )					[7]
Structural Similarity	Tanimoto coefficient = 0.822222222
Tested Species	Homo sapiens (Human)
UniProt ID	PTN11_HUMAN
DBT Name: Trypsin (PRSS)				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	Oleic acid
Biological Activity	IC50 > 200000 nM (tested by experiment)					[6]
Tested Species	Sus scrofa (Pig)
UniProt ID	TRYP_PIG
Primary active transporter (PAT)
DBT Name: Urate exporter (BCRP)				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	Oleic acid
Biological Activity	Inhibition ratio > 60 % (tested by experiment)					[8]
Tested Species	Homo sapiens (Human)
UniProt ID	ABCG2_HUMAN
Potential-driven transporter (PDT)
DBT Name: Norepinephrine transporter (NET)				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	Oleic acid
Biological Activity	IC50 = 27 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	SC6A2_HUMAN
DBT Name: Solute carrier SLCO2B1 (OATPB)				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. 2
Biological Activity	Inhibition ratio = 26 % (tested by experiment)					[9]
Tested Species	Homo sapiens (Human)
UniProt ID	SO2B1_HUMAN
DBT Name: Monoamine transporter VAT2 (VMAT2)				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	Oleic acid
Biological Activity	Ki = 4.7 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	VMAT2_HUMAN
Transmembrane channel/porin (TC/P)
DBT Name: Vanilloid receptor 2 (TrpV2)				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	Oleic acid
Biological Activity	IC50 > 10000 nM (tested by experiment)					[10]
Tested Species	Rattus norvegicus (Rat)
UniProt ID	TRPV2_RAT
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	FD&C blue no. 2
Biological Activity	IC50 > 10 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	ESR1_HUMAN
DBT Name: PPAR-alpha (PPARA)				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	Oleic acid
Biological Activity	IC50 = 600 nM (tested by experiment)					[11]
Tested Species	Homo sapiens (Human)
UniProt ID	PPARA_HUMAN
DBT Name: PPAR-delta (PPARD)				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	Oleic acid
Biological Activity	IC50 = 5300 nM (tested by experiment)					[11]
Tested Species	Homo sapiens (Human)
UniProt ID	PPARD_HUMAN
DBT Name: PPAR-gamma (PPARG)				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	Oleic acid
Biological Activity	IC50 = 4100 nM (tested by experiment)					[11]
Tested Species	Homo sapiens (Human)
UniProt ID	PPARG_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	Oleic acid
Biological Activity	IC50 = 12 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	PRGR_HUMAN
Other protein families (OPF)
DBT Name: Adipocyte lipid-binding protein (ALBP)				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	Oleic acid
Biological Activity	Ki = 1500 nM (tested by experiment)					[12]
Tested Species	Homo sapiens (Human)
UniProt ID	FABP4_HUMAN
DBT Name: Liver lipid-binding protein (L-FABP)				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	Oleic acid
Biological Activity	Ki = 180 nM (tested by experiment)					[13]
Tested Species	Rattus norvegicus (Rat)
UniProt ID	FABPL_RAT
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	Medium-chain triglyceride
Biological Activity	Inhibition ratio > 36 % (tested by experiment)					[14]
Tested Species	Homo sapiens (Human)

References
1	The activities of drug inactive ingredients on biological targets. Science. 2020 Jul 24;369(6502):403-413.
2	Interference by naturally occurring fatty acids in a noncellular enzyme-based aromatase bioassay. J Nat Prod. 2006 Apr; 69(4):700-3.
3	Cox-2 inhibitory effects of naturally occurring and modified fatty acids. J Nat Prod. 2001 Jun; 64(6):745-9.
4	Pharmaceutical excipients inhibit cytochrome P450 activity in cell free systems and after systemic administration. Eur J Pharm Biopharm. 2008 Sep;70(1):279-88.
5	Natural products targeting telomere maintenance. Med Chem Comm. (2011) 2:229-245.
6	Inhibitory activity of unsaturated fatty acids and anacardic acids toward soluble tissue factor-factor VIIa complex. J Nat Prod. 1998 Nov; 61(11):1352-5.
7	US patent application no. 8987474B2, Inhibition of Shp2/PTPN11 Protein Tyrosine Phosphatase by NSC-87877, NSC-117199 and Their Analogs.
8	Oleic acid decreases BCRP mediated efflux of mitoxantrone in Caco-2 cell monolayers. Food Chem Toxicol. 2012 Oct;50(10):3635-45.
9	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.
10	Elongation of the Hydrophobic Chain as a Molecular Switch: Discovery of Capsaicin Derivatives and Endogenous Lipids as Potent Transient Receptor Potential Vanilloid Channel 2 Antagonists. J Med Chem. 2018 Sep 27; 61(18):8255-8281.
11	Molecular properties of fatty acids related to PPAR binding and metabolic diseases. Med Chem Res (2013) 22:3126-3133.
12	The discovery of novel and selective fatty acid binding protein 4 inhibitors by virtual screening and biological evaluation. Bioorg Med Chem. 2016 Sep 15; 24(18):4310-4317.
13	Characterization of the drug binding specificity of rat liver fatty acid binding protein. J Med Chem. 2008 Jul 10; 51(13):3755-64.
14	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.

If you find any error in data or bug in web service, please kindly report it to Dr. Zhang and Dr. Mou.