Literature DB >> 26819662

Potent, Selective, and CNS-Penetrant Tetrasubstituted Cyclopropane Class IIa Histone Deacetylase (HDAC) Inhibitors.

Christopher A Luckhurst1, Perla Breccia1, Andrew J Stott1, Omar Aziz1, Helen L Birch1, Roland W Bürli1, Samantha J Hughes1, Rebecca E Jarvis1, Marieke Lamers1, Philip M Leonard1, Kim L Matthews1, George McAllister1, Scott Pollack1, Elizabeth Saville-Stones1, Grant Wishart1, Dawn Yates1, Celia Dominguez2.   

Abstract

Potent and selective class IIa HDAC tetrasubstituted cyclopropane hydroxamic acid inhibitors were identified with high oral bioavailability that exhibited good brain and muscle exposure. Compound 14 displayed suitable properties for assessment of the impact of class IIa HDAC catalytic site inhibition in preclinical disease models.

Entities:  

Keywords:  CNS exposure; Class IIa HDAC inhibitors; Huntington’s disease; cyclopropanation; hydroxamic acid; tetrasubstituted cyclopropane

Year:  2015        PMID： 26819662      PMCID： PMC4716601          DOI： 10.1021/acsmedchemlett.5b00302

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


  13 in total

Review 1.  Class II histone deacetylases: structure, function, and regulation.

Authors:  N R Bertos; A H Wang; X J Yang
Journal:  Biochem Cell Biol       Date:  2001       Impact factor: 3.626

2.  (Z)- and (E)-[2-Fluoro-2-(hydroxymethyl)cyclopropylidene]methylpurines and -pyrimidines, a new class of methylenecyclopropane analogues of nucleosides: synthesis and antiviral activity.

Authors:  Shaoman Zhou; Earl R Kern; Elizabeth Gullen; Yung-Chi Cheng; John C Drach; Shintaro Matsumi; Hiroaki Mitsuya; Jiri Zemlicka
Journal:  J Med Chem       Date:  2004-12-30       Impact factor: 7.446

3.  Histone deacetylase (HDAC) inhibitor kinetic rate constants correlate with cellular histone acetylation but not transcription and cell viability.

Authors:  Benjamin E L Lauffer; Robert Mintzer; Rina Fong; Susmith Mukund; Christine Tam; Inna Zilberleyb; Birgit Flicke; Allegra Ritscher; Grazyna Fedorowicz; Roxanne Vallero; Daniel F Ortwine; Janet Gunzner; Zora Modrusan; Lars Neumann; Christopher M Koth; Patrick J Lupardus; Joshua S Kaminker; Christopher E Heise; Pascal Steiner
Journal:  J Biol Chem       Date:  2013-07-29       Impact factor: 5.157

4.  Design, synthesis, and biological evaluation of potent and selective class IIa histone deacetylase (HDAC) inhibitors as a potential therapy for Huntington's disease.

Authors:  Roland W Bürli; Christopher A Luckhurst; Omar Aziz; Kim L Matthews; Dawn Yates; Kathy A Lyons; Maria Beconi; George McAllister; Perla Breccia; Andrew J Stott; Stephen D Penrose; Michael Wall; Marieke Lamers; Philip Leonard; Ilka Müller; Christine M Richardson; Rebecca Jarvis; Liz Stones; Samantha Hughes; Grant Wishart; Alan F Haughan; Catherine O'Connell; Tania Mead; Hannah McNeil; Julie Vann; John Mangette; Michel Maillard; Vahri Beaumont; Ignacio Munoz-Sanjuan; Celia Dominguez
Journal:  J Med Chem       Date:  2013-12-05       Impact factor: 7.446

5.  Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs.

Authors:  Kelly M Mahar Doan; Joan E Humphreys; Lindsey O Webster; Stephen A Wring; Larry J Shampine; Cosette J Serabjit-Singh; Kimberly K Adkison; Joseph W Polli
Journal:  J Pharmacol Exp Ther       Date:  2002-12       Impact factor: 4.030

6.  Unraveling the hidden catalytic activity of vertebrate class IIa histone deacetylases.

Authors:  A Lahm; C Paolini; M Pallaoro; M C Nardi; P Jones; P Neddermann; S Sambucini; M J Bottomley; P Lo Surdo; A Carfí; U Koch; R De Francesco; C Steinkühler; P Gallinari
Journal:  Proc Natl Acad Sci U S A       Date:  2007-10-23       Impact factor: 11.205

7.  Structural and functional analysis of the human HDAC4 catalytic domain reveals a regulatory structural zinc-binding domain.

Authors:  Matthew J Bottomley; Paola Lo Surdo; Paolo Di Giovine; Agostino Cirillo; Rita Scarpelli; Federica Ferrigno; Philip Jones; Petra Neddermann; Raffaele De Francesco; Christian Steinkühler; Paola Gallinari; Andrea Carfí
Journal:  J Biol Chem       Date:  2008-07-08       Impact factor: 5.157

8.  SAHA decreases HDAC 2 and 4 levels in vivo and improves molecular phenotypes in the R6/2 mouse model of Huntington's disease.

Authors:  Michal Mielcarek; Caroline L Benn; Sophie A Franklin; Donna L Smith; Ben Woodman; Paul A Marks; Gillian P Bates
Journal:  PLoS One       Date:  2011-11-28       Impact factor: 3.240

Review 9.  HDAC4 as a potential therapeutic target in neurodegenerative diseases: a summary of recent achievements.

Authors:  Michal Mielcarek; Daniel Zielonka; Alisia Carnemolla; Jerzy T Marcinkowski; Fabien Guidez
Journal:  Front Cell Neurosci       Date:  2015-02-24       Impact factor: 5.505

10.  HDAC4 reduction: a novel therapeutic strategy to target cytoplasmic huntingtin and ameliorate neurodegeneration.

Authors:  Michal Mielcarek; Christian Landles; Andreas Weiss; Amyaouch Bradaia; Tamara Seredenina; Linda Inuabasi; Georgina F Osborne; Kristian Wadel; Chrystelle Touller; Rachel Butler; Janette Robertson; Sophie A Franklin; Donna L Smith; Larry Park; Paul A Marks; Erich E Wanker; Eric N Olson; Ruth Luthi-Carter; Herman van der Putten; Vahri Beaumont; Gillian P Bates
Journal:  PLoS Biol       Date:  2013-11-26       Impact factor: 8.029
View more
  8 in total

1.  Development of a Novel, Small-Molecule Brain-Penetrant Histone Deacetylase Inhibitor That Enhances Spatial Memory Formation in Mice.

Authors:  Jawad B Belayet; Sarah Beamish; Mizzanoor Rahaman; Samer Alanani; Rajdeep S Virdi; David N Frick; A F M Towheedur Rahman; Joseph S Ulicki; Sreya Biswas; Leggy A Arnold; M S Rashid Roni; Eric Y Cheng; Douglas A Steeber; Karyn M Frick; M Mahmun Hossain
Journal:  J Med Chem       Date:  2022-02-08       Impact factor: 8.039

2.  Synthesis and Characterization of Reversible Covalent HDAC4 Inhibitors.

Authors:  Anton Frühauf; Benjamin Wolff; Markus Schweipert; Franz-Josef Meyer-Almes
Journal:  Methods Mol Biol       Date:  2023

3.  Fragment-Based Discovery of a Novel, Brain Penetrant, Orally Active HDAC2 Inhibitor.

Authors:  Emiliano Tamanini; Shin Miyamura; Ildiko M Buck; Benjamin D Cons; Lee Dawson; Charlotte East; Takashi Futamura; Shintaro Goto; Charlotte Griffiths-Jones; Tetsuya Hashimoto; Tom D Heightman; Shunpei Ishikawa; Hideki Ito; Yosuke Kaneko; Tatsuya Kawato; Kazumi Kondo; Naoki Kurihara; James M McCarthy; Yukiko Mori; Tsuyoshi Nagase; Yuichiro Nakaishi; Judith Reeks; Akimasa Sato; Patrick Schöpf; Kuninori Tai; Taichi Tamai; Dominic Tisi; Alison J-A Woolford
Journal:  ACS Med Chem Lett       Date:  2022-09-06       Impact factor: 4.632

4.  Target deconvolution of HDAC pharmacopoeia reveals MBLAC2 as common off-target.

Authors:  Severin Lechner; Martin Ian P Malgapo; Christian Grätz; Raphael R Steimbach; Agnes Baron; Patrick Rüther; Simon Nadal; Carmen Stumpf; Christina Loos; Xin Ku; Polina Prokofeva; Ludwig Lautenbacher; Tino Heimburg; Vivian Würf; Chen Meng; Mathias Wilhelm; Wolfgang Sippl; Karin Kleigrewe; Josch K Pauling; Karl Kramer; Aubry K Miller; Michael W Pfaffl; Maurine E Linder; Bernhard Kuster; Guillaume Médard
Journal:  Nat Chem Biol       Date:  2022-04-28       Impact factor: 16.174

Review 5.  Modern Approaches for Asymmetric Construction of Carbon-Fluorine Quaternary Stereogenic Centers: Synthetic Challenges and Pharmaceutical Needs.

Authors:  Yi Zhu; Jianlin Han; Jiandong Wang; Norio Shibata; Mikiko Sodeoka; Vadim A Soloshonok; Jaime A S Coelho; F Dean Toste
Journal:  Chem Rev       Date:  2018-04-02       Impact factor: 60.622

6.  Evaluation of 5-(Trifluoromethyl)-1,2,4-oxadiazole-Based Class IIa HDAC Inhibitors for Huntington's Disease.

Authors:  Andrew J Stott; Michel C Maillard; Vahri Beaumont; David Allcock; Omar Aziz; Alexander H Borchers; Wesley Blackaby; Perla Breccia; Gillian Creighton-Gutteridge; Alan F Haughan; Rebecca E Jarvis; Christopher A Luckhurst; Kim L Matthews; George McAllister; Scott Pollack; Elizabeth Saville-Stones; Amanda J Van de Poël; Huw D Vater; Julie Vann; Rachel Williams; Dawn Yates; Ignacio Muñoz-Sanjuán; Celia Dominguez
Journal:  ACS Med Chem Lett       Date:  2021-02-11       Impact factor: 4.345

7.  Design, synthesis and biological evaluation of a series of CNS penetrant HDAC inhibitors structurally derived from amyloid-β probes.

Authors:  Myeong A Choi; Sun You Park; Hye Yun Chae; Yoojin Song; Chiranjeev Sharma; Young Ho Seo
Journal:  Sci Rep       Date:  2019-09-12       Impact factor: 4.379

8.  In silico Design of Novel Histone Deacetylase 4 Inhibitors: Design Guidelines for Improved Binding Affinity.

Authors:  Shana V Stoddard; Kyra Dodson; Kamesha Adams; Davita L Watkins
Journal:  Int J Mol Sci       Date:  2019-12-28       Impact factor: 5.923
  8 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.