Literature DB >> 24900540

Irreversible 4-Aminopiperidine Transglutaminase 2 Inhibitors for Huntington's Disease.

Michael E Prime1, Frederick A Brookfield1, Stephen M Courtney1, Simon Gaines1, Richard W Marston1, Osamu Ichihara1, Marie Li1, Darshan Vaidya1, Helen Williams1, Anna Pedret-Dunn1, Laura Reed1, Sabine Schaertl2, Leticia Toledo-Sherman3, Maria Beconi3, Douglas Macdonald3, Ignacio Muñoz-Sanjuan3, Celia Dominguez3, John Wityak3.   

Abstract

A new series of potent TG2 inhibitors are reported that employ a 4-aminopiperidine core bearing an acrylamide warhead. We establish the structure-activity relationship of this new series and report on the transglutaminase selectivity and in vitro ADME properties of selected compounds. We demonstrate that the compounds do not conjugate glutathione in an in vitro setting and have superior plasma stability over our previous series.

Entities:  

Keywords:  ADME; Celiac disease; SAR; acrylamides; computer-aided drug design; plasma stability

Year:  2012        PMID： 24900540      PMCID： PMC4025765          DOI： 10.1021/ml3001352

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


  20 in total

Review 1.  Role of tissue transglutaminase in celiac disease.

Authors:  O Molberg; S N McAdam; L M Sollid
Journal:  J Pediatr Gastroenterol Nutr       Date:  2000-03       Impact factor: 2.839

Review 2.  Irreversible inhibitors of tissue transglutaminase.

Authors:  Jeffrey W Keillor; Nicolas Chabot; Isabelle Roy; Amina Mulani; Olivier Leogane; Christophe Pardin
Journal:  Adv Enzymol Relat Areas Mol Biol       Date:  2011

3.  Tissue transglutaminase selectively modifies proteins associated with truncated mutant huntingtin in intact cells.

Authors:  W Chun; M Lesort; J Tucholski; P W Faber; M E MacDonald; C A Ross; G V Johnson
Journal:  Neurobiol Dis       Date:  2001-06       Impact factor: 5.996

Review 4.  Epidermal growth factor receptor irreversible inhibitors: chemical exploration of the cysteine-trap portion.

Authors:  C Carmi; A Lodola; S Rivara; F Vacondio; A Cavazzoni; R R Alfieri; A Ardizzoni; P G Petronini; M Mor
Journal:  Mini Rev Med Chem       Date:  2011-10       Impact factor: 3.862

5.  Structural basis for the guanine nucleotide-binding activity of tissue transglutaminase and its regulation of transamidation activity.

Authors:  Shenping Liu; Richard A Cerione; Jon Clardy
Journal:  Proc Natl Acad Sci U S A       Date:  2002-02-26       Impact factor: 11.205

6.  Discovery and structure-activity relationship of potent and selective covalent inhibitors of transglutaminase 2 for Huntington's disease.

Authors:  Michael E Prime; Ole A Andersen; John J Barker; Mark A Brooks; Robert K Y Cheng; Ian Toogood-Johnson; Stephen M Courtney; Frederick A Brookfield; Christopher J Yarnold; Richard W Marston; Peter D Johnson; Siw F Johnsen; Jordan J Palfrey; Darshan Vaidya; Sayeh Erfan; Osamu Ichihara; Brunella Felicetti; Shilpa Palan; Anna Pedret-Dunn; Sabine Schaertl; Ina Sternberger; Andreas Ebneth; Andreas Scheel; Dirk Winkler; Leticia Toledo-Sherman; Maria Beconi; Douglas Macdonald; Ignacio Muñoz-Sanjuan; Celia Dominguez; John Wityak
Journal:  J Med Chem       Date:  2012-01-27       Impact factor: 7.446

7.  A novel function of tissue-type transglutaminase: protein disulphide isomerase.

Authors:  Go Hasegawa; Motoi Suwa; Yasuo Ichikawa; Tetsuro Ohtsuka; Satoru Kumagai; Masashi Kikuchi; Yoshitaka Sato; Yuji Saito
Journal:  Biochem J       Date:  2003-08-01       Impact factor: 3.857

8.  Transglutaminase activity is related to CAG repeat length in patients with Huntington's disease.

Authors:  L Cariello; T de Cristofaro; L Zanetti; T Cuomo; L Di Maio; G Campanella; S Rinaldi; P Zanetti; R Di Lauro; S Varrone
Journal:  Hum Genet       Date:  1996-12       Impact factor: 4.132

Review 9.  Transglutaminases and neurodegeneration.

Authors:  Thomas M Jeitner; John T Pinto; Boris F Krasnikov; Mark Horswill; Arthur J L Cooper
Journal:  J Neurochem       Date:  2009-05       Impact factor: 5.372

10.  A simple in vitro assay for assessing the reactivity of nitrile containing compounds.

Authors:  Philip A MacFaul; Andrew D Morley; James J Crawford
Journal:  Bioorg Med Chem Lett       Date:  2009-01-01       Impact factor: 2.823
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  6 in total

1.  SAR Development of Lysine-Based Irreversible Inhibitors of Transglutaminase 2 for Huntington's Disease.

Authors:  John Wityak; Michael E Prime; Frederick A Brookfield; Stephen M Courtney; Sayeh Erfan; Siw Johnsen; Peter D Johnson; Marie Li; Richard W Marston; Laura Reed; Darshan Vaidya; Sabine Schaertl; Anna Pedret-Dunn; Maria Beconi; Douglas Macdonald; Ignacio Muñoz-Sanjuan; Celia Dominguez
Journal:  ACS Med Chem Lett       Date:  2012-10-04       Impact factor: 4.345

2.  Irreversible Antagonists for the Adenosine A2B Receptor.

Authors:  Ahmed Temirak; Jonathan G Schlegel; Jan H Voss; Victoria J Vaaßen; Christin Vielmuth; Tobias Claff; Christa E Müller
Journal:  Molecules       Date:  2022-06-13       Impact factor: 4.927

3.  Structure-Activity Relationships of Potent, Targeted Covalent Inhibitors That Abolish Both the Transamidation and GTP Binding Activities of Human Tissue Transglutaminase.

Authors:  Abdullah Akbar; Nicole M R McNeil; Marie R Albert; Viviane Ta; Gautam Adhikary; Karine Bourgeois; Richard L Eckert; Jeffrey W Keillor
Journal:  J Med Chem       Date:  2017-09-14       Impact factor: 7.446

Review 4.  Transglutaminse 2 and EGGL, the protein cross-link formed by transglutaminse 2, as therapeutic targets for disabilities of old age.

Authors:  William Bains
Journal:  Rejuvenation Res       Date:  2013-12       Impact factor: 4.663

5.  An NMR-Guided Screening Method for Selective Fragment Docking and Synthesis of a Warhead Inhibitor.

Authors:  Ram B Khattri; Daniel L Morris; Caroline M Davis; Stephanie M Bilinovich; Andrew J Caras; Matthew J Panzner; Michael A Debord; Thomas C Leeper
Journal:  Molecules       Date:  2016-07-16       Impact factor: 4.411

Review 6.  Strategies towards in vivo imaging of active transglutaminase type 2 using positron emission tomography.

Authors:  Berend van der Wildt; Adriaan A Lammertsma; Benjamin Drukarch; Albert D Windhorst
Journal:  Amino Acids       Date:  2016-07-05       Impact factor: 3.520
  6 in total

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