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Identification
Name Troglitazone
Accession Number DB00197 (APRD00488)
Type small molecule
Groups withdrawn
Description

Troglitazone was withdrawn in 2000 due to risk of hepatotoxicity. It was superseded by pioglitazone and rosiglitazone.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Noscal
Prelay
Resulin
Rezulin
Romglizone
Romozin
Brand mixtures Not Available
Categories
  • Antineoplastic Agents
  • Hypoglycemic Agents
  • Vasodilator Agents
  • Platelet Aggregation Inhibitors
  • Fibrinolytic Agents
CAS number 97322-87-7
Weight Average: 441.54
Monoisotopic: 441.160993669
Chemical Formula C24H27NO5S
InChI Key InChIKey=GXPHKUHSUJUWKP-UHFFFAOYSA-N
InChI
InChI=1S/C24H27NO5S/c1-13-14(2)21-18(15(3)20(13)26)9-10-24(4,30-21)12-29-17-7-5-16(6-8-17)11-19-22(27)25-23(28)31-19/h5-8,19,26H,9-12H2,1-4H3,(H,25,27,28)
Plain Text
IUPAC Name
5-({4-[(6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-1-benzopyran-2-yl)methoxy]phenyl}methyl)-1,3-thiazolidine-2,4-dione
SMILES
CC1=C(C)C2=C(CCC(C)(COC3=CC=C(CC4SC(=O)NC4=O)C=C3)O2)C(C)=C1O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Methoxyphenols
  • Benzopyrans
  • Phenylpropylamines
Substructures
  • Hydroxy Compounds
  • Pyrans
  • Carboxylic Acids and Derivatives
  • Phenols and Derivatives
  • Amino Ketones
  • Ethers
  • Benzene and Derivatives
  • Hydroquinones
  • Methoxyphenols
  • Benzopyrans
  • Thiazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Thiazolidines
  • Anisoles
  • Carboxamides and Derivatives
  • Phenylpropylamines
  • Phenyl Esters
Pharmacology
Indication For the treatment of Type II diabetes mellitus. It is used alone or in combination with a sulfonylurea, metformin, or insulin as an adjunct to diet and exercise.
Pharmacodynamics Troglitazone is an oral antihyperglycemic agent which acts primarily by decreasing insulin resistance. Troglitazone is used in the management of type II diabetes (noninsulin-dependent diabetes mellitus (NIDDM) also known as adult-onset diabetes). It improves sensitivity to insulin in muscle and adipose tissue and inhibits hepatic gluconeogenesis. Troglitazone is not chemically or functionally related to either the sulfonylureas, the biguanides, or the g-glucosidase inhibitors. Troglitazone may be used concomitantly with a sulfonylurea or insulin to improve glycemic control.
Mechanism of action Troglitazone is a thiazolidinedione antidiabetic agent that lowers blood glucose by improving target cell response to insulin. It has a unique mechanism of action that is dependent on the presence of insulin for activity. Troglitazone decreases hepatic glucose output and increases insulin dependent glucose disposal in skeletal muscle. Its mechanism of action is thought to involve binding to nuclear receptors (PPAR) that regulate the transcription of a number of insulin responsive genes critical for the control of glucose and lipid metabolism. Troglitazone is a ligand to both PPARα and PPARγ, with a highter affinity for PPARγ. The drug also contains an α-tocopheroyl moiety, potentially giving it vitamin E-like activity. Troglitazone has been shown to reduce inflammation, and is associated with a decrase in nuclear factor kappa-B (NF-κB) and a concomitant increase in its inhibitor (IκB). NF-κB is an important cellular transcription regulator for the immune response. Unlike sulfonylureas, troglitazone is not an insulin secretagogue.
Absorption Absorbed rapidly. Food increases the extent of absorption by 30% to 85%.
Volume of distribution Not Available
Protein binding > 99% (primarily to serum albumin)
Metabolism A sulfate conjugate metabolite (Metabolite 1) and a quinone metabolite (Metabolite 3) have been detected in the plasma of healthy males. A glucuronide conjugate (Metabolite 2) has been detected in the urine and also in negligible amounts in the plasma. In healthy volunteers and in patients with type 2 diabetes, the steady-state concentration of Metabolite 1 is six to seven times that of troglitazone and Metabolite 3. In in vivo drug interaction studies, troglitazone has been shown to induce cytochrome P450 CYP3A4 at clinically relevant doses.
Route of elimination Not Available
Half life 16-34 hours
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Sankyo usa corp
  • Pfizer pharmaceuticals ltd
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices Not Available
Patents
Country Patent Number Approved Expires (estimated)
United States 5859037 1997-11-13 2017-11-13
United States 5602133 1993-09-15 2013-09-15
Properties
State solid
Experimental Properties
Property Value Source
melting point 184-186 °C Not Available
logP 3.6 Not Available
Predicted Properties
Property Value Source
water solubility 1.21e-03 g/l ALOGPS
logP 4.16 ALOGPS
logP 5.5 ChemAxon
logS -5.6 ALOGPS
pKa (strongest acidic) 6.61 ChemAxon
pKa (strongest basic) -4.6 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 5 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 84.86 ChemAxon
rotatable bond count 5 ChemAxon
refractivity 120.99 ChemAxon
polarizability 47.08 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Aljada A, Garg R, Ghanim H, Mohanty P, Hamouda W, Assian E, Dandona P: Nuclear factor-kappaB suppressive and inhibitor-kappaB stimulatory effects of troglitazone in obese patients with type 2 diabetes: evidence of an antiinflammatory action? J Clin Endocrinol Metab. 2001 Jul;86(7):3250-6. Pubmed
External Links
Resource Link
KEGG Drug D00395 Link_out
PubChem Compound 5591 Link_out
PubChem Substance 46504655 Link_out
ChemSpider 5389 Link_out
ChEBI 9753 Link_out
ChEMBL 9753 Link_out
Therapeutic Targets Database DAP001337 Link_out
PharmGKB PA451799 Link_out
IUPHAR 2693 Link_out
Guide to Pharmacology 2693 Link_out
RxList http://www.rxlist.com/cgi/generic/troglitazone.htm Link_out
Drugs.com http://www.drugs.com/mtm/troglitazone.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Troglitazone Link_out
ATC Codes
  • A10BG01
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (501 KB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Cholestyramine Decreases the effect of troglitazone
Cyclosporine Troglitazone decreases the effect of the immunosuppressant
Ethinyl Estradiol Possible loss of contracepitve effect
Norethindrone Possible loss of contraceptive effect
Food Interactions Not Available
Targets

1. Peroxisome proliferator-activated receptor gamma

Pharmacological action: yes
Actions: agonist

Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the receptor binds to a promoter element in the gene for acyl-CoA oxidase and activates its transcription. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis

Organism class: human
UniProt ID: P37231 Link_out
Gene: PPARG Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Kitamura S, Miyazaki Y, Shinomura Y, Kondo S, Kanayama S, Matsuzawa Y: Peroxisome proliferator-activated receptor gamma induces growth arrest and differentiation markers of human colon cancer cells. Jpn J Cancer Res. 1999 Jan;90(1):75-80. Pubmed
  2. Demetri GD, Fletcher CD, Mueller E, Sarraf P, Naujoks R, Campbell N, Spiegelman BM, Singer S: Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-gamma ligand troglitazone in patients with liposarcoma. Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3951-6. Pubmed
  3. Petrova TV, Akama KT, Van Eldik LJ: Cyclopentenone prostaglandins suppress activation of microglia: down-regulation of inducible nitric-oxide synthase by 15-deoxy-Delta12,14-prostaglandin J2. Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4668-73. Pubmed
  4. Camp HS, Whitton AL, Tafuri SR: PPARgamma activators down-regulate the expression of PPARgamma in 3T3-L1 adipocytes. FEBS Lett. 1999 Mar 26;447(2-3):186-90. Pubmed
  5. Satoh T, Furuta K, Suzuki M, Watanabe Y: Prostaglandin J2 and its metabolites promote neurite outgrowth induced by nerve growth factor in PC12 cells. Biochem Biophys Res Commun. 1999 Apr 29;258(1):50-3. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  7. Baek SJ, Wilson LC, Hsi LC, Eling TE: Troglitazone, a peroxisome proliferator-activated receptor gamma (PPAR gamma ) ligand, selectively induces the early growth response-1 gene independently of PPAR gamma. A novel mechanism for its anti-tumorigenic activity. J Biol Chem. 2003 Feb 21;278(8):5845-53. Epub 2002 Dec 9. Pubmed

2. Long-chain-fatty-acid--CoA ligase 4

Pharmacological action: no
Actions: inhibitor

Activation of long-chain fatty acids for both synthesis of cellular lipids, and degradation via beta-oxidation. Preferentially uses arachidonate and eicosapentaenoate as substrates

Organism class: human
UniProt ID: O60488 Link_out
Gene: ACSL4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Kim JH, Lewin TM, Coleman RA: Expression and characterization of recombinant rat Acyl-CoA synthetases 1, 4, and 5. Selective inhibition by triacsin C and thiazolidinediones. J Biol Chem. 2001 Jul 6;276(27):24667-73. Epub 2001 Apr 23. Pubmed
  2. Lewin TM, Van Horn CG, Krisans SK, Coleman RA: Rat liver acyl-CoA synthetase 4 is a peripheral-membrane protein located in two distinct subcellular organelles, peroxisomes, and mitochondrial-associated membrane. Arch Biochem Biophys. 2002 Aug 15;404(2):263-70. Pubmed
  3. Lewin TM, Kim JH, Granger DA, Vance JE, Coleman RA: Acyl-CoA synthetase isoforms 1, 4, and 5 are present in different subcellular membranes in rat liver and can be inhibited independently. J Biol Chem. 2001 Jul 6;276(27):24674-9. Epub 2001 Apr 23. Pubmed

3. Plasminogen activator inhibitor 1

Pharmacological action: unknown
Actions: antagonist

This inhibitor acts as 'bait' for tissue plasminogen activator, urokinase, and protein C. Its rapid interaction with TPA may function as a major control point in the regulation of fibrinolysis

Organism class: human
UniProt ID: P05121 Link_out
Gene: SERPINE1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Sobel BE: Insulin resistance and thrombosis: a cardiologist’s view. Am J Cardiol. 1999 Jul 8;84(1A):37J-41J. Pubmed
  2. Gottschling-Zeller H, Rohrig K, Hauner H: Troglitazone reduces plasminogen activator inhibitor-1 expression and secretion in cultured human adipocytes. Diabetologia. 2000 Mar;43(3):377-83. Pubmed
  3. Nordt TK, Peter K, Bode C, Sobel BE: Differential regulation by troglitazone of plasminogen activator inhibitor type 1 in human hepatic and vascular cells. J Clin Endocrinol Metab. 2000 Apr;85(4):1563-8. Pubmed
  4. Kato K, Yamada D, Midorikawa S, Sato W, Watanabe T: Improvement by the insulin-sensitizing agent, troglitazone, of abnormal fibrinolysis in type 2 diabetes mellitus. Metabolism. 2000 May;49(5):662-5. Pubmed
  5. Kruszynska YT, Yu JG, Olefsky JM, Sobel BE: Effects of troglitazone on blood concentrations of plasminogen activator inhibitor 1 in patients with type 2 diabetes and in lean and obese normal subjects. Diabetes. 2000 Apr;49(4):633-9. Pubmed

4. Equilibrative nucleoside transporter 1

Pharmacological action: no
Actions: inhibitor

Mediates both influx and efflux of nucleosides across the membrane (equilibrative transporter). It is sensitive (ES) to low concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR) and is sodium-independent. It has a higher affinity for adenosine. Inhibited by dipyridamole and dilazep (anticancer chemotherapeutics drugs)

Organism class: human
UniProt ID: Q99808 Link_out
Gene: SLC29A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Leung GP, Man RY, Tse CM: Effect of thiazolidinediones on equilibrative nucleoside transporter-1 in human aortic smooth muscle cells. Biochem Pharmacol. 2005 Aug 1;70(3):355-62. Pubmed

5. Estrogen-related receptor gamma

Pharmacological action: no
Actions: inverse agonist

Orphan receptor. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response elements

Organism class: human
UniProt ID: P62508 Link_out
Gene: ESRRG Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wang Y, Fang F, Wong CW: Troglitazone is an estrogen-related receptor alpha and gamma inverse agonist. Biochem Pharmacol. 2010 Jul 1;80(1):80-5. Epub 2010 Mar 16. Pubmed

6. Steroid hormone receptor ERR1

Pharmacological action: no
Actions: inverse agonist

Binds to an ERR-alpha response element (ERRE) containing a single consensus half-site, 5'-TNAAGGTCA-3'. Can bind to the medium-chain acyl coenzyme A dehydrogenase (MCAD) response element NRRE-1 and may act as an important regulator of MCAD promoter. Binds to the C1 region of the lactoferrin gene promoter. Requires dimerization and the coactivator, PGC-1A, for full activity. The ERRalpha/PGC1alpha complex is a regulator of energy metabolism

Organism class: human
UniProt ID: P11474 Link_out
Gene: ESRRA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wang Y, Fang F, Wong CW: Troglitazone is an estrogen-related receptor alpha and gamma inverse agonist. Biochem Pharmacol. 2010 Jul 1;80(1):80-5. Epub 2010 Mar 16. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate, inhibitor, inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2C8

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Schoch GA, Yano JK, Sansen S, Dansette PM, Stout CD, Johnson EF: Determinants of cytochrome P450 2C8 substrate binding: structures of complexes with montelukast, troglitazone, felodipine, and 9-cis-retinoic acid. J Biol Chem. 2008 Jun 20;283(25):17227-37. Epub 2008 Apr 15. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. UDP-glucuronosyltransferase 1-1

Actions: substrate

UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX- alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate

UniProt ID: P22309 Link_out
Gene: UGT1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Watanabe Y, Nakajima M, Yokoi T: Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9. Pubmed

4. Cytochrome P450 2C19

Actions: substrate, inhibitor

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 19A1

Actions: inhibitor

Catalyzes the formation of aromatic C18 estrogens from C19 androgens

UniProt ID: P11511 Link_out
Gene: CYP19A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 1A1

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P04798 Link_out
Gene: CYP1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

7. Cytochrome P450 2B6

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20813 Link_out
Gene: CYP2B6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

8. Cytochrome P450 2C9

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

9. Cytochrome P450 3A5

Actions: inhibitor, inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

10. Cytochrome P450 3A7

Actions: inhibitor, inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

11. UDP-glucuronosyltransferase 1-3

Actions: substrate

UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds

UniProt ID: P35503 Link_out
Gene: UGT1A3 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Watanabe Y, Nakajima M, Yokoi T: Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9. Pubmed

12. UDP-glucuronosyltransferase 1-4

Actions: substrate

UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX- alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate

UniProt ID: P22310 Link_out
Gene: UGT1A4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Watanabe Y, Nakajima M, Yokoi T: Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9. Pubmed

13. UDP-glucuronosyltransferase 1-6

Actions: substrate, inhibitor
UniProt ID: P19224 Link_out

References:
  1. Watanabe Y, Nakajima M, Yokoi T: Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9. Pubmed
  2. Ito M, Yamamoto K, Sato H, Fujiyama Y, Bamba T: Inhibitory effect of troglitazone on glucuronidation catalyzed by human uridine diphosphate-glucuronosyltransferase 1A6. Eur J Clin Pharmacol. 2001 Mar;56(12):893-5. Pubmed

14. UDP-glucuronosyltransferase 1-7

Actions: substrate
UniProt ID: Q9HAW7 Link_out

References:
  1. Watanabe Y, Nakajima M, Yokoi T: Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9. Pubmed

15. UDP-glucuronosyltransferase 1-8

Actions: substrate

UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds

UniProt ID: Q9HAW9 Link_out
Gene: UGT1A8 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Watanabe Y, Nakajima M, Yokoi T: Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9. Pubmed

16. UDP-glucuronosyltransferase 1-9

Actions: substrate

UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols

UniProt ID: O60656 Link_out
Gene: UGT1A9 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Watanabe Y, Nakajima M, Yokoi T: Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9. Pubmed
  2. Barbier O, Villeneuve L, Bocher V, Fontaine C, Torra IP, Duhem C, Kosykh V, Fruchart JC, Guillemette C, Staels B: The UDP-glucuronosyltransferase 1A9 enzyme is a peroxisome proliferator-activated receptor alpha and gamma target gene. J Biol Chem. 2003 Apr 18;278(16):13975-83. Epub 2003 Feb 11. Pubmed

17. UDP-glucuronosyltransferase 1-10

Actions: substrate

UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds

UniProt ID: Q9HAW8 Link_out
Gene: UGT1A10 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Watanabe Y, Nakajima M, Yokoi T: Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9. Pubmed

18. UDP-glucuronosyltransferase 2B7

Actions: substrate

Its unique specificity for 3,4-catechol estrogens and estriol suggests it may play an important role in regulating the level and activity of these potent and active estrogen metabolites

UniProt ID: P16662 Link_out
Gene: UGT2B7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Watanabe Y, Nakajima M, Yokoi T: Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9. Pubmed

19. UDP-glucuronosyltransferase 2B15

Actions: substrate
UniProt ID: P54855 Link_out

References:
  1. Watanabe Y, Nakajima M, Yokoi T: Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9. Pubmed
Transporters

1. Bile salt export pump

Actions: inhibitor

Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes

UniProt ID: O95342 Link_out
Gene: ABCB11 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Fluorescent substrates of sister-P-glycoprotein (BSEP) evaluated as markers of active transport and inhibition: evidence for contingent unequal binding sites. Pharm Res. 2003 Apr;20(4):537-44. Pubmed
  2. Funk C, Pantze M, Jehle L, Ponelle C, Scheuermann G, Lazendic M, Gasser R: Troglitazone-induced intrahepatic cholestasis by an interference with the hepatobiliary export of bile acids in male and female rats. Correlation with the gender difference in troglitazone sulfate formation and the inhibition of the canalicular bile salt export pump (Bsep) by troglitazone and troglitazone sulfate. Toxicology. 2001 Oct 5;167(1):83-98. Pubmed
  3. Saito H, Osumi M, Hirano H, Shin W, Nakamura R, Ishikawa T: Technical pitfalls and improvements for high-speed screening and QSAR analysis to predict inhibitors of the human bile salt export pump (ABCB11/BSEP). AAPS J. 2009 Sep;11(3):581-9. Epub 2009 Aug 18. Pubmed

2. Solute carrier organic anion transporter family member 1B1

Actions: inhibitor

Mediates the Na(+)-independent transport of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. May play an important role in the clearance of bile acids and organic anions from the liver

UniProt ID: Q9Y6L6 Link_out
Gene: SLCO1B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Nozawa T, Sugiura S, Nakajima M, Goto A, Yokoi T, Nezu J, Tsuji A, Tamai I: Involvement of organic anion transporting polypeptides in the transport of troglitazone sulfate: implications for understanding troglitazone hepatotoxicity. Drug Metab Dispos. 2004 Mar;32(3):291-4. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19