Details of the Drug Formulation (DFM)

General Information of DFM (ID: F14852)
Name
Naloxegol 12.5 mg tablet
Company
AstraZeneca
Active Pharmaceutical Ingredient (API) Naloxegol API Info click to show the detail info of this API
Irritable bowel syndrome ICD-11: DD91 Approved
Drug Inactive Ingredient (DIGs)
DIG ID DIG Info DIG Name DIG Functional Class
E03SQI DIG Info Carmellose sodium Disintegrant
E09YYN DIG Info Eisenoxyd Colorant
E02FBG DIG Info Ferrosoferric oxide Colorant
E01UTP DIG Info Magnesium stearate lubricant
E0Q6DQ DIG Info Mannitol Diluent ...
E0PC2L DIG Info Polyethylene glycol 400 Coating agent ...
E0U9NK DIG Info Propyl gallate Antimicrobial preservative ...
E05BSD DIG Info Titanium dioxide Coating agent ...
E0H2SC DIG Info Water Solvent
Full List of Biological Targets of DIG (DBTs) Regulated by DIG(s) in This DFM
      Oxidoreductase (ORase)
            DBT Name: N1-methyl adenine demethylase (FTO) 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 Propyl gallate
                    Biological Activity Ki = 3 uM (tested by experiment) [1]
                    Tested Species Homo sapiens (Human)
                    UniProt ID FTO_HUMAN
            DBT Name: Arachidonate 5-lipoxygenase (ALOX5) 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 Propyl gallate
                    Biological Activity Ki = 0.43 uM (tested by experiment) [1]
                    Tested Species Homo sapiens (Human)
                    UniProt ID LOX5_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 for Assessing the Biological Activity of the Studied DIG on This DBT
                    Interacting DIG Propyl gallate
                    Biological Activity IC50 = 7.2 uM (tested by experiment) [1]
                    Tested Species Homo sapiens (Human)
                    UniProt ID PGH2_HUMAN
            DBT Name: Lysine-specific demethylase 4C (KDM4C) 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 Propyl gallate
                    Biological Activity Ki = 39 uM (tested by experiment) [1]
                    Tested Species Homo sapiens (Human)
                    UniProt ID KDM4C_HUMAN
            DBT Name: Tyrosine 3-monooxygenase (TH) 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 Propyl gallate
                    Biological Activity Ki = 1.9 uM (tested by experiment) [1]
                    Tested Species Homo sapiens (Human)
                    UniProt ID TY3H_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 Magnesium stearate
                    Biological Activity Protein expression downregulation (tested by experiment) [2]
                    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) [2]
                    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) [2]
                    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) [3]
                    Tested Species Homo sapiens (Human)
                    UniProt ID CP3A4_HUMAN
      Cation-dependent O-methyltransferase
            DBT Name: Catechol O-methyltransferase (COMT) 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 Propyl gallate
                    Biological Activity Ki = 0.015 uM (tested by experiment) [1]
                    Tested Species Homo sapiens (Human)
                    UniProt ID COMT_HUMAN
      Hydrolase (HDase)
            DBT Name: Phosphodiesterase 4D (PDE4D) 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 Propyl gallate
                    Biological Activity IC50 = 26 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) [4]
                    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) [5]
                    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) [6]
                    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) [7]
                    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 for Assessing the Biological Activity of the Studied DIG on This DBT
                    Interacting DIG Propyl gallate
                    Biological Activity Inhibition ratio = 29.6 % (tested by experiment) [8]
                    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) [9]
                    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) [9]
                    Tested Species Homo sapiens (Human)
                    UniProt ID SO1A2_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 ) [10]
                    Structural Similarity Tanimoto coefficient = 0.804878049
                    Tested Species Homo sapiens (Human)
                    UniProt ID GLRA1_HUMAN
      Other protein families (OPF)
            DBT Name: Anthrax toxin receptor 2 (CMG-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 Propyl gallate
                    Biological Activity IC50 > 300000 nM (tested by experiment) [11]
                    Tested Species Homo sapiens (Human)
                    UniProt ID ANTR2_HUMAN
References
1 The activities of drug inactive ingredients on biological targets. Science. 2020 Jul 24;369(6502):403-413.
2 Effects of commonly used excipients on the expression of CYP3A4 in colon and liver cells. Pharm Res. 2010 Aug;27(8):1703-12.
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 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.
5 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.
6 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.
7 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.
8 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.
9 Pharmaceutical excipients influence the function of human uptake transporting proteins. Mol Pharm. 2012 Sep 4;9(9):2577-81.
10 Pharmacological property optimization for allosteric ligands: A medicinal chemistry perspective. Bioorg Med Chem Lett. 2017 Jun 1; 27(11):2239-2258.
11 1,2,3,4,6-Penta-O-galloyl--D-glucopyranose inhibits angiogenesis via inhibition of capillary morphogenesis gene 2. J Med Chem. 2013 Mar 14; 56(5):1940-5.

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