Details of the Drug Formulation (DFM)

General Information of DFM (ID: F20263)
Name
Sirolimus 0.5 mg tablet
Company
Zydus Pharmaceuticals
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 ...
E0PE9M DIG Info Crospovidone Disintegrant
E0M0IE DIG Info Ferric hydroxide oxide yellow Colorant
E00PSA DIG Info Glyceryl monooleate Bioadhesive material ...
E08XEK DIG Info Hydrazine yellow Colorant
E00DHW DIG Info Lactose monohydrate Binding agent ...
E09KOV DIG Info Poloxamer 188 Emulsifying agent ...
E0Q7IF DIG Info Povidone Binding agent ...
E0Q3PU DIG Info Saccharose Binding agent ...
E0QY1F DIG Info Talc Anticaking agent ...
E05BSD DIG Info Titanium dioxide Coating agent ...
E09WWS DIG Info Tocopheryl acetate Antioxidant
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 (1) for Assessing the Biological Activity of the Studied DIG on This DBT
                    Interacting DIG Crospovidone
                    Biological Activity Protein expression downregulation (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 Poloxamer 188
                    Biological Activity IC50 = 60 uM (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 Povidone
                    Biological Activity IC50 = 107 uM (tested by experiment) [4]
                    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 Povidone
                    Biological Activity Protein expression upregulation (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) [4]
                    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) [4]
                    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) [4]
                    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) [4]
                    Tested Species Homo sapiens (Human)
                    UniProt ID CP3A5_HUMAN
      Transferase (TFase)
            DBT Name: Diacylglycerol kinase alpha (DGKA) 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 Glyceryl monooleate
                    Biological Activity Ki = 91000 nM (tested by experiment) [5]
                    Tested Species Homo sapiens (Human)
                    UniProt ID DGKA_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 ) [6]
                    Structural Similarity Tanimoto coefficient = 0.777777778
                    Tested Species Homo sapiens (Human)
                    UniProt ID TYDP2_HUMAN
      Lyase/isomerase/ligase (L/I/G)
            DBT Name: Cholesterol 25-hydroxylase (CYP1A2) 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 Povidone
                    Biological Activity IC50 = 78.3 uM (tested by experiment) [4]
                    Tested Species Homo sapiens (Human)
                    UniProt ID CP1A2_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 Glyceryl monooleate
                    Biological Activity Inhibition ratio = 62 % (tested by experiment) [7]
                    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 = 53 % (tested by experiment) [8]
                    Tested Species Homo sapiens (Human)
                    UniProt ID MRP2_HUMAN
               Experiment (3) 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
            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 Glyceryl monooleate
                    Biological Activity Protein expression downregulation = 39.1 % (tested by experiment) [10]
                    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 Glyceryl monooleate
                    Biological Activity Inhibition ratio = 39 % (tested by experiment) [10]
                    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 Glyceryl monooleate
                    Biological Activity Inhibition ratio = 63 % (tested by experiment) [10]
                    Tested Species Homo sapiens (Human)
                    UniProt ID MDR1_HUMAN ; MDR3_HUMAN ; ABCB5_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) [11]
                    Tested Species Homo sapiens (Human)
            DBT Name: Prostate cancer LNCaP cells (LNCaP) 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 Tocopheryl acetate
                    Biological Activity EC50 = 38000 nM (estimated based on the structural similarity with CHEMBL242495 ) [12]
                    Structural Similarity Tanimoto coefficient = 0.933333333
                    Tested Species Homo sapiens (Human)
                    Cellosaurus ID CVCL_0395
            DBT Name: Breast cancer MCF7 cells (MCF7) 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 Tocopheryl acetate
                    Biological Activity IC50 > 500000 nM (tested by experiment) [13]
                    Tested Species Homo sapiens (Human)
                    Cellosaurus ID CVCL_0031
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 Effects of commonly used excipients on the expression of CYP3A4 in colon and liver cells. Pharm Res. 2010 Aug;27(8):1703-12.
4 Mediation of in vitro cytochrome p450 activity by common pharmaceutical excipients. Mol Pharm. 2013 Jul 1;10(7):2739-48.
5 Identification of a novel DGKalpha inhibitor for XLP-1 therapy by virtual screening. Eur J Med Chem. 2019; 164:378-390.
6 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.
7 Effects of monoglycerides on rhodamine 123 accumulation, estradiol 17 beta-D-glucuronide bidirectional transport and MRP2 protein expression within Caco-2 cells. J Pharm Pharm Sci. 2008;11(3):45-62.
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 Effects of monoglycerides on P-glycoprotein: modulation of the activity and expression in Caco-2 cell monolayers. Mol Pharm. Sep-Oct 2008;5(5):863-75.
11 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.
12 First pharmacophore-based identification of androgen receptor down-regulating agents: discovery of potent anti-prostate cancer agents. Bioorg Med Chem. 2007 May 15; 15(10):3413-21.
13 Design and synthesis of analogs of vitamin E: antiproliferative activity against human breast adenocarcinoma cells. Bioorg Med Chem Lett. 1998 Sep 22; 8(18):2433-8.

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