General Information of DFM (ID: F20268)
Name	Sirolimus 1 mg tablet
Company	American Health Packaging
Active Pharmaceutical Ingredient (API)	Sirolimus		API Info click to show the detail info of this API
	Lymphangioleiomyomatosis		ICD-11: CB07	Approved
Drug Inactive Ingredient (DIGs)
	DIG ID	DIG Info	DIG Name	DIG Functional Class
	E01OUP	DIG Info	Allura red AC dye	Colorant
	E0LT2O	DIG Info	Alpha-tocopherol	Antimicrobial preservative ...
	E0A1CS	DIG Info	Ammonia	Alkalizing agent
	E00DHW	DIG Info	Lactose monohydrate	Binding agent ...
	E01UTP	DIG Info	Magnesium stearate	lubricant
	E0Q6DQ	DIG Info	Mannitol	Diluent ...
	E09KOV	DIG Info	Poloxamer 188	Emulsifying agent ...
	E0M1JK	DIG Info	Propylene glycol	Antimicrobial preservative ...
	E0Q3PU	DIG Info	Saccharose	Binding 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 1A (5HT1A)				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	Allura red AC dye
Biological Activity	IC50 = 19 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	5HT1A_HUMAN
DBT Name: Dopamine D1 receptor (DRD1)				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	Allura red AC dye
Biological Activity	IC50 = 29 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	DRD1_HUMAN
Oxidoreductase (ORase)
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 for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Allura red AC dye
Biological Activity	IC50 = 26 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 for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Poloxamer 188
Biological Activity	IC50 = 750 uM (tested by experiment)					[2]
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)					[3]
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	Magnesium stearate
Biological Activity	Protein expression downregulation (tested by experiment)					[4]
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	Poloxamer 188
Biological Activity	IC50 = 60 uM (tested by experiment)					[5]
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	Poloxamer 188
Biological Activity	IC50 = 203.7 uM (tested by experiment)					[5]
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 for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Poloxamer 188
Biological Activity	IC50 = 244.8 uM (tested by experiment)					[5]
Tested Species	Homo sapiens (Human)
UniProt ID	CP2C9_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	Poloxamer 188
Biological Activity	EC50 = 387.6 uM (tested by experiment)					[5]
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	Poloxamer 188
Biological Activity	IC50 = 210 uM (tested by experiment)					[5]
Tested Species	Homo sapiens (Human)
UniProt ID	CP3A5_HUMAN
Transferase (TFase)
DBT Name: Glutathione S-transferase P (GSTP1)				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	Alpha-tocopherol
Biological Activity	IC50 = 500 nM (tested by experiment)					[6]
Tested Species	Homo sapiens (Human)
UniProt ID	GSTP1_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	Allura red AC dye
Biological Activity	IC50 > 10 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	ACES_HUMAN
DBT Name: Protein-tyrosine phosphatase 1B (PTPN1)				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	Allura red AC dye
Biological Activity	IC50 = 33000 nM (tested by experiment)					[7]
Tested Species	Homo sapiens (Human)
UniProt ID	PTN1_HUMAN
Experiment (2) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Allura red AC dye
Biological Activity	IC50 = 410000 nM (tested by experiment)					[7]
Tested Species	Saccharomyces cerevisiae (Yeast)
UniProt ID	PTP1_YEAST
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	Allura red AC dye
Biological Activity	IC50 = 17 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	PDE3A_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	Poloxamer 188
Biological Activity	Inhibition ratio = 53 % (tested by experiment)					[8]
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	Poloxamer 188
Biological Activity	Inhibition ratio > 55 % (tested by experiment)					[9]
Tested Species	Homo sapiens (Human)
UniProt ID	MRP2_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	Allura red AC dye
Biological Activity	Inhibition ratio = 96.52 % (tested by experiment)					[10]
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	Allura red AC dye
Biological Activity	Ki = 2.59 uM (tested by experiment)					[10]
Tested Species	Homo sapiens (Human)
UniProt ID	SO2B1_HUMAN
Experiment (3) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Allura red AC dye
Biological Activity	Ki = 4.7 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	SO2B1_HUMAN
Transmembrane channel/porin (TC/P)
DBT Name: Glycine receptor alpha-1 (GLRA1)				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	Mannitol
Biological Activity	EC50 = 12589.25 nM (estimated based on the structural similarity with CHEMBL604608 )					[11]
Structural Similarity	Tanimoto coefficient = 0.804878049
Tested Species	Homo sapiens (Human)
UniProt ID	GLRA1_HUMAN
DBT Name: GABA(A) receptor alpha-1 (GABRA1)				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	Allura red AC dye
Biological Activity	IC50 = 22 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	GBRA1_HUMAN
Nuclear receptor (NR)
DBT Name: Androgen receptor (AR)				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	Allura red AC dye
Biological Activity	IC50 = 28 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	ANDR_HUMAN
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	Allura red AC dye
Biological Activity	IC50 = 15 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	Allura red AC dye
Biological Activity	IC50 = 30 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	PRGR_HUMAN
Other protein families (OPF)
DBT Name: Thrombopoietin receptor (MPL)				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	Allura red AC dye
Biological Activity	EC50 = 300 nM (estimated based on the structural similarity with CHEMBL123373 )					[12]
Structural Similarity	Tanimoto coefficient = 0.925714286
Tested Species	Homo sapiens (Human)
UniProt ID	TPOR_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	Poloxamer 188
Biological Activity	Chylomicron secretion downregulation (tested by experiment)					[13]
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	Nonionic surfactants are strong inhibitors of cytochrome P450 3A biotransformation activity in vitro and in vivo. Eur J Pharm Sci. 2009 Mar 2;36(4-5):401-11.
3	Pharmaceutical excipients inhibit cytochrome P450 activity in cell free systems and after systemic administration. Eur J Pharm Biopharm. 2008 Sep;70(1):279-88.
4	Effects of commonly used excipients on the expression of CYP3A4 in colon and liver cells. Pharm Res. 2010 Aug;27(8):1703-12.
5	Mediation of in vitro cytochrome p450 activity by common pharmaceutical excipients. Mol Pharm. 2013 Jul 1;10(7):2739-48.
6	Reviewing Hit Discovery Literature for Difficult Targets: Glutathione Transferase Omega-1 as an Example. J Med Chem. 2018 Sep 13; 61(17):7448-7470.
7	Evans Blue and other dyes as protein tyrosine phosphatase inhibitors. Bioorg Med Chem Lett. 2004 Apr 19; 14(8):1923-6.
8	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.
9	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.
10	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.
11	Pharmacological property optimization for allosteric ligands: A medicinal chemistry perspective. Bioorg Med Chem Lett. 2017 Jun 1; 27(11):2239-2258.
12	Hydrazinonaphthalene and azonaphthalene thrombopoietin mimics are nonpeptidyl promoters of megakaryocytopoiesis. J Med Chem. 2001 Oct 25; 44(22):3730-45.
13	The effects of pluronics block copolymers and Cremophor EL on intestinal lipoprotein processing and the potential link with P-glycoprotein in Caco-2 cells. Pharm Res. 2003 Jul;20(7):1085-92.

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