دورية أكاديمية
Quantitative Chemical Proteomic Profiling of the in Vivo Targets of Reactive Drug Metabolites.
العنوان: | Quantitative Chemical Proteomic Profiling of the in Vivo Targets of Reactive Drug Metabolites. |
---|---|
المؤلفون: | Whitby LR; The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute , 10550 N. Torrey Pines Rd., La Jolla, California 92307, United States., Obach RS; Pfizer Worldwide Research and Development , Eastern Point Road, Groton, Connecticut 06340, United States., Simon GM; Vividion Therapeutics , 3033 Science Park Rd Suite D, San Diego, California 92121, United States., Hayward MM; Pfizer Worldwide Research and Development , Eastern Point Road, Groton, Connecticut 06340, United States., Cravatt BF; The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute , 10550 N. Torrey Pines Rd., La Jolla, California 92307, United States. |
المصدر: | ACS chemical biology [ACS Chem Biol] 2017 Aug 18; Vol. 12 (8), pp. 2040-2050. Date of Electronic Publication: 2017 Jun 21. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
اللغة: | English |
بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 101282906 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1554-8937 (Electronic) Linking ISSN: 15548929 NLM ISO Abbreviation: ACS Chem Biol Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Washington, D.C. : American Chemical Society, c2006- |
مواضيع طبية MeSH: | Chemical and Drug Induced Liver Injury* , Drug Delivery Systems* , Proteogenomics*, Acetaminophen/*toxicity , Hepatocytes/*drug effects, Acetaminophen/chemistry ; Acetaminophen/pharmacology ; Animals ; Liver/injuries ; Mice ; Molecular Structure |
مستخلص: | Idiosyncratic liver toxicity represents an important problem in drug research and pharmacotherapy. Reactive drug metabolites that modify proteins are thought to be a principal factor in drug-induced liver injury. Here, we describe a quantitative chemical proteomic method to identify the targets of reactive drug metabolites in vivo. Treating mice with clickable analogues of four representative hepatotoxic drugs, we demonstrate extensive covalent binding that is confined primarily to the liver. Each drug exhibited a distinct target profile that, in certain cases, showed strong enrichment for specific metabolic pathways (e.g., lipid/sterol pathways for troglitazone). Site-specific proteomics revealed that acetaminophen reacts with high stoichiometry with several conserved, functional (seleno)cysteine residues throughout the liver proteome. Our findings thus provide an advanced experimental framework to characterize the proteomic reactivity of drug metabolites in vivo, revealing target profiles that may help to explain mechanisms and identify risk factors for drug-induced liver injury. |
References: | Nat Methods. 2014 Jan;11(1):79-85. (PMID: 24292485) Toxicol Lett. 2014 Apr 21;226(2):163-72. (PMID: 24560604) Drug Metab Rev. 2015 Feb;47(1):56-70. (PMID: 25410913) Biochem Pharmacol. 2016 Feb 15;102:34-44. (PMID: 26686580) Drug Metab Rev. 1997 Feb-May;29(1-2):39-57. (PMID: 9187510) J Biol Chem. 2015 Dec 11;290(50):29941-52. (PMID: 26504085) Annu Rev Pathol. 2015;10:173-94. (PMID: 25387057) Handb Exp Pharmacol. 2010;(196 ):369-405. (PMID: 20020268) J Pharmacol Exp Ther. 1995 Mar;272(3):984-90. (PMID: 7891353) Toxicol Sci. 2010 Jun;115(2):307-21. (PMID: 20071422) Chem Res Toxicol. 2008 Jan;21(1):117-28. (PMID: 18052106) Clin Pharmacol Ther. 2014 Nov;96(5):589-98. (PMID: 25068506) J Biol Chem. 2011 Dec 16;286(50):42937-48. (PMID: 22016385) J Biol Chem. 2015 Oct 30;290(44):26491-507. (PMID: 26370081) Nat Chem Biol. 2014 Sep;10 (9):760-767. (PMID: 25038787) J Hepatol. 2011 Apr;54(4):773-94. (PMID: 21145849) Nat Prod Rep. 2016 May 4;33(5):681-708. (PMID: 27098809) Chem Biol. 2015 Oct 22;22(10 ):1394-405. (PMID: 26496688) Chem Biol Interact. 1984 Mar;48(3):349-66. (PMID: 6713598) Chem Res Toxicol. 2001 Jan;14(1):62-70. (PMID: 11170509) Nature. 2016 Jun 15;534(7608):570-4. (PMID: 27309814) Methods. 2013 Jun 15;61(3):277-86. (PMID: 23567750) Nat Rev Drug Discov. 2011 Apr;10(4):292-306. (PMID: 21455238) Toxicol Sci. 2013 Oct;135(2):390-401. (PMID: 23897987) Nat Chem Biol. 2005 Oct;1(5):252-62. (PMID: 16408053) J Biol Chem. 2016 May 6;291(19):10021-31. (PMID: 27002142) Chem Res Toxicol. 2008 Jan;21(1):189-205. (PMID: 18052110) Drug Saf. 2015 May;38(5):437-53. (PMID: 25822400) Toxicol Appl Pharmacol. 2015 Jul 1;286(1):1-9. (PMID: 25818599) J Am Chem Soc. 2009 Aug 5;131(30):10692-700. (PMID: 19583257) Chem Res Toxicol. 2016 Nov 21;29(11):1857-1864. (PMID: 27680534) Chem Res Toxicol. 2011 Sep 19;24(9):1345-410. (PMID: 21702456) Chem Res Toxicol. 2012 May 21;25(5):1145-54. (PMID: 22462724) EMBO J. 1998 May 1;17(9):2596-606. (PMID: 9564042) Chem Res Toxicol. 1995 Apr-May;8(3):403-13. (PMID: 7578927) Oncoscience. 2014 Jan 02;1(1):95-110. (PMID: 25593990) Drug Metab Rev. 2012 Feb;44(1):18-33. (PMID: 21939431) Nucleic Acids Res. 2016 Jan 4;44(D1):D336-42. (PMID: 26578592) Cell Chem Biol. 2017 Feb 16;24(2):133-140. (PMID: 28132892) Eur J Intern Med. 2016 Mar;28:9-16. (PMID: 26827101) Biochem Pharmacol. 1990 Mar 1;39(5):911-8. (PMID: 2310416) Pharmacol Rev. 2013 Mar 08;65(2):779-808. (PMID: 23476052) J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Nov 25;797(1-2):63-90. (PMID: 14630144) Pharmacoepidemiol Drug Saf. 2012 Nov;21(11):1139-54. (PMID: 22761169) J Biol Chem. 1998 Jul 10;273(28):17940-53. (PMID: 9651401) Chem Res Toxicol. 2014 May 19;27(5):882-94. (PMID: 24661219) Nature. 2010 Dec 9;468(7325):790-5. (PMID: 21085121) J Am Chem Soc. 2003 Apr 23;125(16):4686-7. (PMID: 12696868) Angew Chem Int Ed Engl. 2002 Jul 15;41(14):2596-9. (PMID: 12203546) Nat Rev Drug Discov. 2005 Jun;4(6):489-99. (PMID: 15931258) J Biol Chem. 2015 Jan 16;290(3):1885-97. (PMID: 25416785) |
معلومات مُعتمدة: | R01 CA087660 United States CA NCI NIH HHS; R37 CA087660 United States CA NCI NIH HHS |
المشرفين على المادة: | 362O9ITL9D (Acetaminophen) |
تواريخ الأحداث: | Date Created: 20170622 Date Completed: 20180220 Latest Revision: 20181113 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC5626524 |
DOI: | 10.1021/acschembio.7b00346 |
PMID: | 28636309 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1554-8937 |
---|---|
DOI: | 10.1021/acschembio.7b00346 |