Literature DB >> 24900424

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

John Wityak1, Michael E Prime2, Frederick A Brookfield2, Stephen M Courtney2, Sayeh Erfan2, Siw Johnsen2, Peter D Johnson2, Marie Li2, Richard W Marston2, Laura Reed2, Darshan Vaidya2, Sabine Schaertl3, Anna Pedret-Dunn2, Maria Beconi1, Douglas Macdonald1, Ignacio Muñoz-Sanjuan1, Celia Dominguez1.   

Abstract

We report a series of irreversible transglutaminase 2 inhibitors starting from a known lysine dipeptide bearing an acrylamide warhead. We established new SARs resulting in compounds demonstrating improved potency and better physical and calculated properties. Transglutaminase selectivity profiling and in vitro ADME properties of selected compounds are also reported.

Entities:  

Keywords:  acrylamides; celiac disease; in vitro ADME; plasma stability; polar surface area

Year:  2012        PMID： 24900424      PMCID： PMC4025666          DOI： 10.1021/ml300241m

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


  24 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

2.  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 3.  The importance of integrating basic and clinical research toward the development of new therapies for Huntington disease.

Authors:  Ignacio Munoz-Sanjuan; Gillian P Bates
Journal:  J Clin Invest       Date:  2011-02-01       Impact factor: 14.808

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

Authors:  Michael E Prime; Frederick A Brookfield; Stephen M Courtney; Simon Gaines; Richard W Marston; Osamu Ichihara; Marie Li; Darshan Vaidya; Helen Williams; Anna Pedret-Dunn; Laura Reed; Sabine Schaertl; Leticia Toledo-Sherman; Maria Beconi; Douglas Macdonald; Ignacio Muñoz-Sanjuan; Celia Dominguez; John Wityak
Journal:  ACS Med Chem Lett       Date:  2012-08-09       Impact factor: 4.345

5.  Molecular properties that influence the oral bioavailability of drug candidates.

Authors:  Daniel F Veber; Stephen R Johnson; Hung-Yuan Cheng; Brian R Smith; Keith W Ward; Kenneth D Kopple
Journal:  J Med Chem       Date:  2002-06-06       Impact factor: 7.446

6.  Evaluation of novel dipeptide-bound alpha,beta-unsaturated amides and epoxides as irreversible inhibitors of guinea pig liver transglutaminase.

Authors:  C Marrano; P de Macédo; J W Keillor
Journal:  Bioorg Med Chem       Date:  2001-07       Impact factor: 3.641

7.  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

8.  Tissue transglutaminase overexpression does not modify the disease phenotype of the R6/2 mouse model of Huntington's disease.

Authors:  Ashish Kumar; Andrew Kneynsberg; Janusz Tucholski; Giselle Perry; Thomas van Groen; Peter J Detloff; Mathieu Lesort
Journal:  Exp Neurol       Date:  2012-06-12       Impact factor: 5.330

9.  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

Review 10.  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
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  9 in total

1.  Structure-activity relationships of hydrophobic alkyl acrylamides as tissue transglutaminase inhibitors.

Authors:  Alana M M Rangaswamy; Pauline Navals; Eric W J Gates; Sammir Shad; Sarah K I Watt; Jeffrey W Keillor
Journal:  RSC Med Chem       Date:  2022-01-26

2.  Application of a Fluorescence Anisotropy-Based Assay to Quantify Transglutaminase 2 Activity in Cell Lysates.

Authors:  Sandra Hauser; Paul Sommerfeld; Johanna Wodtke; Christoph Hauser; Paul Schlitterlau; Jens Pietzsch; Reik Löser; Markus Pietsch; Robert Wodtke
Journal:  Int J Mol Sci       Date:  2022-04-19       Impact factor: 6.208

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.  In vivo evaluation of two tissue transglutaminase PET tracers in an orthotopic tumour xenograft model.

Authors:  Berend van der Wildt; Micha M M Wilhelmus; Wissam Beaino; Esther J M Kooijman; Robert C Schuit; John G J M Bol; John J P Breve; Ralf Pasternack; Adriaan A Lammertsma; Albert D Windhorst; Benjamin Drukarch
Journal:  EJNMMI Res       Date:  2018-05-25       Impact factor: 3.138

6.  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

7.  The Role of Transglutaminase 2 in the Radioresistance of Melanoma Cells.

Authors:  Julia Aepler; Johanna Wodtke; Robert Wodtke; Cathleen Haase-Kohn; Reik Löser; Jens Pietzsch; Sandra Hauser
Journal:  Cells       Date:  2022-04-14       Impact factor: 7.666

8.  NMR-based investigations of acyl-functionalized piperazines concerning their conformational behavior in solution.

Authors:  Robert Wodtke; Janine Steinberg; Martin Köckerling; Reik Löser; Constantin Mamat
Journal:  RSC Adv       Date:  2018-12-06       Impact factor: 4.036

Review 9.  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
  9 in total

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