General Information of DFM (ID: F20261)
Name	Sirolimus 0.5 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
	E09QIG	DIG Info	Citric acid monohydrate	Acidulant ...
	E0M0IE	DIG Info	Ferric hydroxide oxide yellow	Colorant
	E08XEK	DIG Info	Hydrazine yellow	Colorant
	E00DHW	DIG Info	Lactose monohydrate	Binding agent ...
	E09KOV	DIG Info	Poloxamer 188	Emulsifying agent ...
	E0Q3PU	DIG Info	Saccharose	Binding agent ...
	E0QY1F	DIG Info	Talc	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: Opioid receptor mu (OPRM1)				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	Hydrazine yellow
Biological Activity	IC50 = 16 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	OPRM_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	Hydrazine yellow
Biological Activity	IC50 = 23 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	DRD1_HUMAN
Oxidoreductase (ORase)
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 for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Poloxamer 188
Biological Activity	IC50 = 60 uM (tested by experiment)					[3]
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)					[3]
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)					[3]
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)					[3]
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)					[3]
Tested Species	Homo sapiens (Human)
UniProt ID	CP3A5_HUMAN
Hydrolase (HDase)
DBT Name: Tyrosyl-DNA phosphodiesterase 2 (TDP2)				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	Hydrazine yellow
Biological Activity	IC50 = 3500 nM (estimated based on the structural similarity with CHEMBL3813826 )					[4]
Structural Similarity	Tanimoto coefficient = 0.777777778
Tested Species	Homo sapiens (Human)
UniProt ID	TYDP2_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)					[5]
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)					[6]
Tested Species	Homo sapiens (Human)
UniProt ID	MRP2_HUMAN
Transmembrane channel/porin (TC/P)
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	Hydrazine yellow
Biological Activity	IC50 = 13 uM (tested by experiment)					[1]
Tested Species	Homo sapiens (Human)
UniProt ID	GBRA1_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)					[7]
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	Mediation of in vitro cytochrome p450 activity by common pharmaceutical excipients. Mol Pharm. 2013 Jul 1;10(7):2739-48.
4	Discovery of selective inhibitors of tyrosyl-DNA phosphodiesterase 2 by targeting the enzyme DNA-binding cleft. Bioorg Med Chem Lett. 2016 Jul 15; 26(14):3232-3236.
5	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.
6	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.
7	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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