Literature DB >> 24900560

Structure-Based Design of Irreversible Human KAT II Inhibitors: Discovery of New Potency-Enhancing Interactions.

Jamison B Tuttle1, Marie Anderson1, Bruce M Bechle1, Brian M Campbell1, Cheng Chang1, Amy B Dounay1, Edelweiss Evrard1, Kari R Fonseca1, Xinmin Gan1, Somraj Ghosh1, Weldon Horner1, Larry C James1, Ji-Young Kim1, Laura A McAllister1, Jayvardhan Pandit1, Vinod D Parikh1, Brian J Rago1, Michelle A Salafia1, Christine A Strick1, Laura E Zawadzke1, Patrick R Verhoest1.   

Abstract

A series of aryl hydroxamates recently have been disclosed as irreversible inhibitors of kynurenine amino transferase II (KAT II), an enzyme that may play a role in schizophrenia and other psychiatric and neurological disorders. The utilization of structure-activity relationships (SAR) in conjunction with X-ray crystallography led to the discovery of hydroxamate 4, a disubstituted analogue that has a significant potency enhancement due to a novel interaction with KAT II. The use of k inact/K i to assess potency was critical for understanding the SAR in this series and for identifying compounds with improved pharmacodynamic profiles.

Entities:  

Keywords:  aryl hydrocarbon receptor; dose response modeling; hydroxamic acid; in vivo microdialysis; irreversible inhibition; kynurenic acid; kynurenine amino transferase; schizophrenia

Year:  2012        PMID： 24900560      PMCID： PMC4027135          DOI： 10.1021/ml300237v

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  18 in total

1.  Evaluation of enzyme inhibitors in drug discovery. A guide for medicinal chemists and pharmacologists.

Authors:  Robert A Copeland
Journal:  Methods Biochem Anal       Date:  2005

2.  Modulators of the kynurenine pathway of tryptophan metabolism: synthesis and preliminary biological evaluation of (S)-4-(ethylsulfonyl)benzoylalanine, a potent and selective kynurenine aminotransferase II (KAT II) inhibitor.

Authors:  Roberto Pellicciari; Rosa C Rizzo; Gabriele Costantino; Maura Marinozzi; Laura Amori; Paolo Guidetti; Hui-Qiu Wu; Robert Schwarcz
Journal:  ChemMedChem       Date:  2006-05       Impact factor: 3.466

3.  Cation-pi interactions in protein-protein interfaces.

Authors:  Peter B Crowley; Adel Golovin
Journal:  Proteins       Date:  2005-05-01

Review 4.  Kynurenic acid: a metabolite with multiple actions and multiple targets in brain and periphery.

Authors:  Flavio Moroni; Andrea Cozzi; Maria Sili; Guido Mannaioni
Journal:  J Neural Transm (Vienna)       Date:  2012-01-04       Impact factor: 3.575

5.  Elevated levels of kynurenic acid in the cerebrospinal fluid of patients with bipolar disorder.

Authors:  Sara K Olsson; Martin Samuelsson; Peter Saetre; Leif Lindström; Erik G Jönsson; Conny Nordin; Göran Engberg; Sophie Erhardt; Mikael Landén
Journal:  J Psychiatry Neurosci       Date:  2010-05       Impact factor: 6.186

6.  Cation-pi interactions in structural biology.

Authors:  J P Gallivan; D A Dougherty
Journal:  Proc Natl Acad Sci U S A       Date:  1999-08-17       Impact factor: 11.205

7.  The brain metabolite kynurenic acid inhibits alpha7 nicotinic receptor activity and increases non-alpha7 nicotinic receptor expression: physiopathological implications.

Authors:  C Hilmas; E F Pereira; M Alkondon; A Rassoulpour; R Schwarcz; E X Albuquerque
Journal:  J Neurosci       Date:  2001-10-01       Impact factor: 6.167

8.  Elevated levels of kynurenic acid in the cerebrospinal fluid of male patients with schizophrenia.

Authors:  L K Nilsson; K R Linderholm; G Engberg; L Paulson; K Blennow; L H Lindström; C Nordin; A Karanti; P Persson; S Erhardt
Journal:  Schizophr Res       Date:  2005-08-25       Impact factor: 4.939

9.  Increased cortical kynurenate content in schizophrenia.

Authors:  R Schwarcz; A Rassoulpour; H Q Wu; D Medoff; C A Tamminga; R C Roberts
Journal:  Biol Psychiatry       Date:  2001-10-01       Impact factor: 13.382

10.  Characterization of human brain kynurenine aminotransferases using [3H]kynurenine as a substrate.

Authors:  W Schmidt; P Guidetti; E Okuno; R Schwarcz
Journal:  Neuroscience       Date:  1993-07       Impact factor: 3.590
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  10 in total

1.  High resolution crystal structures of human kynurenine aminotransferase-I bound to PLP cofactor, and in complex with aminooxyacetate.

Authors:  Naveed A Nadvi; Noeris K Salam; Joohong Park; Fady N Akladios; Vimal Kapoor; Charles A Collyer; Mark D Gorrell; William Bret Church
Journal:  Protein Sci       Date:  2017-03-06       Impact factor: 6.725

2.  Ligand-enabled β-C-H arylation of α-amino acids using a simple and practical auxiliary.

Authors:  Gang Chen; Toshihiko Shigenari; Pankaj Jain; Zhipeng Zhang; Zhong Jin; Jian He; Suhua Li; Claudio Mapelli; Michael M Miller; Michael A Poss; Paul M Scola; Kap-Sun Yeung; Jin-Quan Yu
Journal:  J Am Chem Soc       Date:  2015-03-03       Impact factor: 15.419

3.  Oral administration of a specific kynurenic acid synthesis (KAT II) inhibitor attenuates evoked glutamate release in rat prefrontal cortex.

Authors:  D M Bortz; H-Q Wu; R Schwarcz; J P Bruno
Journal:  Neuropharmacology       Date:  2017-04-15       Impact factor: 5.250

4.  Rational Optimization of Mechanism-Based Inhibitors through Determination of the Microscopic Rate Constants of Inactivation.

Authors:  Carter G Eiden; Kimberly M Maize; Barry C Finzel; John D Lipscomb; Courtney C Aldrich
Journal:  J Am Chem Soc       Date:  2017-05-18       Impact factor: 15.419

Review 5.  Major Developments in the Design of Inhibitors along the Kynurenine Pathway.

Authors:  Kelly R Jacobs; Gloria Castellano-Gonzalez; Gilles J Guillemin; David B Lovejoy
Journal:  Curr Med Chem       Date:  2017       Impact factor: 4.530

6.  Structural basis for substrate specificity in ArnB. A key enzyme in the polymyxin resistance pathway of Gram-negative bacteria.

Authors:  Myeongseon Lee; Marcelo C Sousa
Journal:  Biochemistry       Date:  2014-01-24       Impact factor: 3.162

7.  Structure of the PLP-Form of the Human Kynurenine Aminotransferase II in a Novel Spacegroup at 1.83 Å Resolution.

Authors:  Alireza Nematollahi; Guanchen Sun; Stephen J Harrop; Jane R Hanrahan; W Bret Church
Journal:  Int J Mol Sci       Date:  2016-03-25       Impact factor: 5.923

8.  Crystal structures of Mycobacterium tuberculosis HspAT and ArAT reveal structural basis of their distinct substrate specificities.

Authors:  Nazia Nasir; Avishek Anant; Rajan Vyas; Bichitra Kumar Biswal
Journal:  Sci Rep       Date:  2016-01-07       Impact factor: 4.379

Review 9.  Kynurenine Aminotransferase Isozyme Inhibitors: A Review.

Authors:  Alireza Nematollahi; Guanchen Sun; Gayan S Jayawickrama; W Bret Church
Journal:  Int J Mol Sci       Date:  2016-06-15       Impact factor: 5.923

10.  Heterocyclic Cathinones as Inhibitors of Kynurenine Aminotransferase II-Design, Synthesis, and Evaluation.

Authors:  Michal Maryška; Lucie Svobodová; Wim Dehaen; Martina Hrabinová; Michaela Rumlová; Ondřej Soukup; Martin Kuchař
Journal:  Pharmaceuticals (Basel)       Date:  2021-12-10
  10 in total

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