Literature DB >> 24900670

Discovery of BAF312 (Siponimod), a Potent and Selective S1P Receptor Modulator.

Shifeng Pan1, Nathanael S Gray1, Wenqi Gao1, Yuan Mi1, Yi Fan1, Xing Wang1, Tove Tuntland1, Jianwei Che1, Sophie Lefebvre1, Yu Chen1, Alan Chu1, Klaus Hinterding2, Anne Gardin2, Peter End2, Peter Heining2, Christian Bruns2, Nigel G Cooke2, Barbara Nuesslein-Hildesheim2.   

Abstract

A novel series of alkoxyimino derivatives as S1P1 agonists were discovered through de novo design using FTY720 as the chemical starting point. Extensive structure-activity relationship studies led to the discovery of (E)-1-(4-(1-(((4-cyclohexyl-3-(trifluoromethyl)benzyl)oxy)imino)ethyl)-2-ethylbenzyl)azetidine-3-carboxylic acid (32, BAF312, Siponimod), which has recently completed phase 2 clinical trials in patients with relapsing-remitting multiple sclerosis.

Entities:  

Keywords:  S1P receptor; S1P1 agonist; lymphocytes

Year:  2013        PMID： 24900670      PMCID： PMC4027137          DOI： 10.1021/ml300396r

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


  21 in total

1.  Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists.

Authors:  Suzanne Mandala; Richard Hajdu; James Bergstrom; Elizabeth Quackenbush; Jenny Xie; James Milligan; Rosemary Thornton; Gan-Ju Shei; Deborah Card; CarolAnn Keohane; Mark Rosenbach; Jeffrey Hale; Christopher L Lynch; Kathleen Rupprecht; William Parsons; Hugh Rosen
Journal:  Science       Date:  2002-03-28       Impact factor: 47.728

2.  Fused tricyclic indoles as S1P₁ agonists with robust efficacy in animal models of autoimmune disease.

Authors:  Daniel J Buzard; Sangdon Han; Luis Lopez; Andrew Kawasaki; Jeanne Moody; Lars Thoresen; Brett Ullman; Juerg Lehmann; Imelda Calderon; Xiuwen Zhu; Tawfik Gharbaoui; Dipanjan Sengupta; Ashwin Krishnan; Yinghong Gao; Jeff Edwards; Jeremy Barden; Michael Morgan; Khawja Usmani; Chuan Chen; Abu Sadeque; Jayant Thatte; Michelle Solomon; Lixia Fu; Kevin Whelan; Ling Liu; Hussien Al-Shamma; Joel Gatlin; Minh Le; Charles Xing; Sheryll Espinola; Robert M Jones
Journal:  Bioorg Med Chem Lett       Date:  2012-05-07       Impact factor: 2.823

3.  A monoselective sphingosine-1-phosphate receptor-1 agonist prevents allograft rejection in a stringent rat heart transplantation model.

Authors:  Shifeng Pan; Yuan Mi; Charles Pally; Christian Beerli; Alice Chen; Danilo Guerini; Klaus Hinterding; Barbara Nuesslein-Hildesheim; Tove Tuntland; Sophie Lefebvre; Yi Liu; Wenqi Gao; Alan Chu; Volker Brinkmann; Christian Bruns; Markus Streiff; Catherine Cannet; Nigel Cooke; Nathanael Gray
Journal:  Chem Biol       Date:  2006-11

Review 4.  Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis.

Authors:  Volker Brinkmann; Andreas Billich; Thomas Baumruker; Peter Heining; Robert Schmouder; Gordon Francis; Shreeram Aradhye; Pascale Burtin
Journal:  Nat Rev Drug Discov       Date:  2010-10-29       Impact factor: 84.694

Review 5.  Chemokines, sphingosine-1-phosphate, and cell migration in secondary lymphoid organs.

Authors:  Jason G Cyster
Journal:  Annu Rev Immunol       Date:  2005       Impact factor: 28.527

6.  FTY720: placebo-controlled study of the effect on cardiac rate and rhythm in healthy subjects.

Authors:  Robert Schmouder; Denise Serra; Yibin Wang; John M Kovarik; John DiMarco; Thomas L Hunt; Marie-Claude Bastien
Journal:  J Clin Pharmacol       Date:  2006-08       Impact factor: 3.126

Review 7.  Synthetic sphingosine 1-phosphate receptor modulators--opportunities and potential pitfalls.

Authors:  Martin H Bolli; Cyrille Lescop; Oliver Nayler
Journal:  Curr Top Med Chem       Date:  2011       Impact factor: 3.295

Review 8.  The outs and the ins of sphingosine-1-phosphate in immunity.

Authors:  Sarah Spiegel; Sheldon Milstien
Journal:  Nat Rev Immunol       Date:  2011-05-06       Impact factor: 53.106

9.  Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate.

Authors:  M Germana Sanna; Jiayu Liao; Euijung Jo; Christopher Alfonso; Min-Young Ahn; Melissa S Peterson; Bill Webb; Sophie Lefebvre; Jerold Chun; Nathanael Gray; Hugh Rosen
Journal:  J Biol Chem       Date:  2004-01-19       Impact factor: 5.157

10.  Sphingosine 1-phosphate (S1P) regulates vascular contraction via S1P3 receptor: investigation based on a new S1P3 receptor antagonist.

Authors:  Akira Murakami; Hiroshi Takasugi; Shinya Ohnuma; Yuuki Koide; Atsuko Sakurai; Satoshi Takeda; Takeshi Hasegawa; Jun Sasamori; Takashi Konno; Kenji Hayashi; Yoshiaki Watanabe; Koji Mori; Yoshimichi Sato; Atsuo Takahashi; Naoki Mochizuki; Nobuyuki Takakura
Journal:  Mol Pharmacol       Date:  2010-01-22       Impact factor: 4.436
View more
  43 in total

Review 1.  Modulators of the Sphingosine 1-phosphate receptor 1.

Authors:  Mariangela Urbano; Miguel Guerrero; Hugh Rosen; Edward Roberts
Journal:  Bioorg Med Chem Lett       Date:  2013-09-29       Impact factor: 2.823

Review 2.  Pharmacological Approaches to the Management of Secondary Progressive Multiple Sclerosis.

Authors:  A Nandoskar; J Raffel; A S Scalfari; T Friede; R S Nicholas
Journal:  Drugs       Date:  2017-05       Impact factor: 9.546

3.  Identification and Preclinical Pharmacology of BMS-986104: A Differentiated S1P1 Receptor Modulator in Clinical Trials.

Authors:  T G Murali Dhar; Hai-Yun Xiao; Jenny Xie; Lois D Lehman-McKeeman; Dauh-Rurng Wu; Marta Dabros; Xiaoxia Yang; Tracy L Taylor; Xia D Zhou; Elizabeth M Heimrich; Rochelle Thomas; Kim W McIntyre; Bethanne Warrack; Hong Shi; Paul C Levesque; Jia L Zhu; James Hennan; Praveen Balimane; Zheng Yang; Anthony M Marino; Georgia Cornelius; Celia J D'Arienzo; Arvind Mathur; Ding Ren Shen; Mary Ellen Cvijic; Luisa Salter-Cid; Joel C Barrish; Percy H Carter; Alaric J Dyckman
Journal:  ACS Med Chem Lett       Date:  2016-01-19       Impact factor: 4.345

4.  Harnessing the power of yeast to elucidate the role of sphingolipids in metabolic and signaling processes pertinent to psychiatric disorders.

Authors:  Shyamalagauri Jadhav; Miriam L Greenberg
Journal:  Clin Lipidol       Date:  2014-11-01

5.  Siponimod enriches regulatory T and B lymphocytes in secondary progressive multiple sclerosis.

Authors:  Qi Wu; Elizabeth A Mills; Qin Wang; Catherine A Dowling; Caitlyn Fisher; Britany Kirch; Steven K Lundy; David A Fox; Yang Mao-Draayer
Journal:  JCI Insight       Date:  2020-02-13

Review 6.  Sphingosine 1-Phosphate Receptor Modulators for the Treatment of Multiple Sclerosis.

Authors:  Burhan Z Chaudhry; Jeffrey A Cohen; Devon S Conway
Journal:  Neurotherapeutics       Date:  2017-10       Impact factor: 7.620

7.  Sphingosine 1-phosphate receptor modulation suppresses pathogenic astrocyte activation and chronic progressive CNS inflammation.

Authors:  Veit Rothhammer; Jessica E Kenison; Emily Tjon; Maisa C Takenaka; Kalil Alves de Lima; Davis M Borucki; Chun-Cheih Chao; Annabel Wilz; Manon Blain; Luke Healy; Jack Antel; Francisco J Quintana
Journal:  Proc Natl Acad Sci U S A       Date:  2017-02-06       Impact factor: 11.205

8.  Discovery of APD334: Design of a Clinical Stage Functional Antagonist of the Sphingosine-1-phosphate-1 Receptor.

Authors:  Daniel J Buzard; Sun Hee Kim; Luis Lopez; Andrew Kawasaki; Xiuwen Zhu; Jeanne Moody; Lars Thoresen; Imelda Calderon; Brett Ullman; Sangdon Han; Juerg Lehmann; Tawfik Gharbaoui; Dipanjan Sengupta; Lorene Calvano; Antonio Garrido Montalban; You-An Ma; Carleton Sage; Yinghong Gao; Graeme Semple; Jeff Edwards; Jeremy Barden; Michael Morgan; Weichao Chen; Khawja Usmani; Chuan Chen; Abu Sadeque; Ronald J Christopher; Jayant Thatte; Lixia Fu; Michelle Solomon; David Mills; Kevin Whelan; Hussien Al-Shamma; Joel Gatlin; Minh Le; Ibragim Gaidarov; Todd Anthony; David J Unett; Anthony Blackburn; Jaimie Rueter; Scott Stirn; Dominic P Behan; Robert M Jones
Journal:  ACS Med Chem Lett       Date:  2014-11-04       Impact factor: 4.345

9.  Sphingosine-1-phosphate receptor 1 activation in astrocytes contributes to neuropathic pain.

Authors:  Zhoumou Chen; Timothy M Doyle; Livio Luongo; Tally M Largent-Milnes; Luigino Antonio Giancotti; Grant Kolar; Silvia Squillace; Serena Boccella; John K Walker; Alexander Pendleton; Sarah Spiegel; William L Neumann; Todd W Vanderah; Daniela Salvemini
Journal:  Proc Natl Acad Sci U S A       Date:  2019-05-08       Impact factor: 11.205

10.  Siponimod Chips Away at Progressive MS.

Authors:  Erin E Longbrake; David A Hafler
Journal:  Cell       Date:  2019-12-12       Impact factor: 41.582
View more

北京卡尤迪生物科技股份有限公司 © 2022-2023.