Literature DB >> 25210004

Discovery of a highly selective PLD2 inhibitor (ML395): a new probe with improved physiochemical properties and broad-spectrum antiviral activity against influenza strains.

Matthew C O'Reilly1, Thomas H Oguin, Sarah A Scott, Paul G Thomas, Charles W Locuson, Ryan D Morrison, J Scott Daniels, H Alex Brown, Craig W Lindsley.   

Abstract

Further chemical optimization of the halopemide-derived family of dual phospholipase D1/2 (PLD1/2) inhibitors afforded ML395 (VU0468809), a potent, >80-fold PLD2 selective allosteric inhibitor (cellular PLD1, IC50 >30,000 nM; cellular PLD2, IC50 =360 nM). Moreover, ML395 possesses an attractive in vitro DMPK profile, improved physiochemical properties, ancillary pharmacology (Eurofins Panel) cleaner than any other reported PLD inhibitor, and has been found to possess interesting activity as an antiviral agent in cellular assays against a range of influenza strains (H1, H3, H5 and H7).
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Entities:  

Keywords:  PLD2; antivirals; inhibitors; lipids; phospholipase D

Mesh：

Substances：

Year:  2014        PMID： 25210004      PMCID： PMC4535312          DOI： 10.1002/cmdc.201402333

Source DB:  PubMed          Journal:  ChemMedChem        ISSN： 1860-7179            Impact factor:   3.466


  11 in total

1.  Design, synthesis, and biological evaluation of halogenated N-(2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)ethyl)benzamides: discovery of an isoform-selective small molecule phospholipase D2 inhibitor.

Authors:  Robert R Lavieri; Sarah A Scott; Paige E Selvy; Kwangho Kim; Satyawan Jadhav; Ryan D Morrison; J Scott Daniels; H Alex Brown; Craig W Lindsley
Journal:  J Med Chem       Date:  2010-09-23       Impact factor: 7.446

2.  Phospholipase D facilitates efficient entry of influenza virus, allowing escape from innate immune inhibition.

Authors:  Thomas H Oguin; Shalini Sharma; Amanda D Stuart; Susu Duan; Sarah A Scott; Carrie K Jones; J Scott Daniels; Craig W Lindsley; Paul G Thomas; H Alex Brown
Journal:  J Biol Chem       Date:  2014-07-27       Impact factor: 5.157

Review 3.  Phospholipase D: enzymology, functionality, and chemical modulation.

Authors:  Paige E Selvy; Robert R Lavieri; Craig W Lindsley; H Alex Brown
Journal:  Chem Rev       Date:  2011-09-22       Impact factor: 60.622

4.  The clinical significance of halopemide, a dopamine-blocker related to the butyrophenones.

Authors:  H De Cuyper; H M van Praag; D Verstraeten
Journal:  Neuropsychobiology       Date:  1984       Impact factor: 2.328

5.  Design and synthesis of isoform-selective phospholipase D (PLD) inhibitors. Part II. Identification of the 1,3,8-triazaspiro[4,5]decan-4-one privileged structure that engenders PLD2 selectivity.

Authors:  Robert Lavieri; Sarah A Scott; Jana A Lewis; Paige E Selvy; Michelle D Armstrong; H Alex Brown; Craig W Lindsley
Journal:  Bioorg Med Chem Lett       Date:  2009-03-06       Impact factor: 2.823

6.  Biochemical analysis of phospholipase D.

Authors:  H Alex Brown; Lee G Henage; Anita M Preininger; Yun Xiang; John H Exton
Journal:  Methods Enzymol       Date:  2007       Impact factor: 1.600

7.  Development of dual PLD1/2 and PLD2 selective inhibitors from a common 1,3,8-Triazaspiro[4.5]decane Core: discovery of Ml298 and Ml299 that decrease invasive migration in U87-MG glioblastoma cells.

Authors:  Matthew C O'Reilly; Sarah A Scott; Kyle A Brown; Thomas H Oguin; Paul G Thomas; J Scott Daniels; Ryan Morrison; H Alex Brown; Craig W Lindsley
Journal:  J Med Chem       Date:  2013-03-13       Impact factor: 7.446

8.  Design and synthesis of isoform-selective phospholipase D (PLD) inhibitors. Part I: Impact of alternative halogenated privileged structures for PLD1 specificity.

Authors:  Jana A Lewis; Sarah A Scott; Robert Lavieri; Jason R Buck; Paige E Selvy; Sydney L Stoops; Michelle D Armstrong; H Alex Brown; Craig W Lindsley
Journal:  Bioorg Med Chem Lett       Date:  2009-02-20       Impact factor: 2.823

9.  Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness.

Authors:  Sarah A Scott; Paige E Selvy; Jason R Buck; Hyekyung P Cho; Tracy L Criswell; Ashley L Thomas; Michelle D Armstrong; Carlos L Arteaga; Craig W Lindsley; H Alex Brown
Journal:  Nat Chem Biol       Date:  2009-01-11       Impact factor: 15.040

10.  Association between adverse clinical outcome in human disease caused by novel influenza A H7N9 virus and sustained viral shedding and emergence of antiviral resistance.

Authors:  Yunwen Hu; Shuihua Lu; Zhigang Song; Wei Wang; Pei Hao; Jianhua Li; Xiaonan Zhang; Hui-Ling Yen; Bisheng Shi; Tao Li; Wencai Guan; Lei Xu; Yi Liu; Sen Wang; Xiaoling Zhang; Di Tian; Zhaoqin Zhu; Jing He; Kai Huang; Huijie Chen; Lulu Zheng; Xuan Li; Jie Ping; Bin Kang; Xiuhong Xi; Lijun Zha; Yixue Li; Zhiyong Zhang; Malik Peiris; Zhenghong Yuan
Journal:  Lancet       Date:  2013-05-29       Impact factor: 79.321
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  7 in total

1.  Further evaluation of novel structural modifications to scaffolds that engender PLD isoform selective inhibition.

Authors:  Matthew C O'Reilly; Sarah A Scott; H Alex Brown; Craig W Lindsley
Journal:  Bioorg Med Chem Lett       Date:  2014-11-15       Impact factor: 2.823

2.  Human PLD structures enable drug design and characterization of isoenzyme selectivity.

Authors:  Claire M Metrick; Emily A Peterson; Joseph C Santoro; Istvan J Enyedy; Paramasivam Murugan; TeYu Chen; Klaus Michelsen; Michael Cullivan; Kerri A Spilker; P Rajesh Kumar; Tricia L May-Dracka; Jayanth V Chodaparambil
Journal:  Nat Chem Biol       Date:  2020-02-10       Impact factor: 15.040

3.  Crystal structure of plant PLDα1 reveals catalytic and regulatory mechanisms of eukaryotic phospholipase D.

Authors:  Jianxu Li; Fang Yu; Hui Guo; Renxue Xiong; Wenjing Zhang; Fangyuan He; Minhua Zhang; Peng Zhang
Journal:  Cell Res       Date:  2019-10-16       Impact factor: 46.297

Review 4.  Progress of small molecular inhibitors in the development of anti-influenza virus agents.

Authors:  Xiaoai Wu; Xiuli Wu; Qizheng Sun; Chunhui Zhang; Shengyong Yang; Lin Li; Zhiyun Jia
Journal:  Theranostics       Date:  2017-02-08       Impact factor: 11.556

Review 5.  Targeting phospholipase D in cancer, infection and neurodegenerative disorders.

Authors:  H Alex Brown; Paul G Thomas; Craig W Lindsley
Journal:  Nat Rev Drug Discov       Date:  2017-02-17       Impact factor: 84.694

6.  Fate of Liposomes in the Presence of Phospholipase C and D: From Atomic to Supramolecular Lipid Arrangement.

Authors:  Margaret N Holme; M Harunur Rashid; Michael R Thomas; Hanna M G Barriga; Karla Luise Herpoldt; Richard K Heenan; Cécile A Dreiss; José Leobardo Bañuelos; Hai-Nan Xie; Irene Yarovsky; Molly M Stevens
Journal:  ACS Cent Sci       Date:  2018-08-06       Impact factor: 14.553

7.  Spatiotemporal control of phosphatidic acid signaling with optogenetic, engineered phospholipase Ds.

Authors:  Reika Tei; Jeremy M Baskin
Journal:  J Cell Biol       Date:  2020-03-02       Impact factor: 10.539
  7 in total

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