2. Academic Validation
  3. Discovery of APD334: Design of a Clinical Stage Functional Antagonist of the Sphingosine-1-phosphate-1 Receptor

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

  • ACS Med Chem Lett. 2014 Nov 4;5(12):1313-7. doi: 10.1021/ml500389m.
Daniel J Buzard 1,  Sun Hee Kim 1,  Luis Lopez 1,  Andrew Kawasaki 1,  Xiuwen Zhu 1,  Jeanne Moody 1,  Lars Thoresen 1,  Imelda Calderon 1,  Brett Ullman 1,  Sangdon Han 1,  Juerg Lehmann 1,  Tawfik Gharbaoui 1,  Dipanjan Sengupta 1,  Lorene Calvano 1,  Antonio Garrido Montalban 1,  You-An Ma 1,  Carleton Sage 1,  Yinghong Gao 1,  Graeme Semple 1,  Jeff Edwards 1,  Jeremy Barden 1,  Michael Morgan 1,  Weichao Chen 1,  Khawja Usmani 1,  Chuan Chen 1,  Abu Sadeque 1,  Ronald J Christopher 1,  Jayant Thatte 1,  Lixia Fu 1,  Michelle Solomon 1,  David Mills 1,  Kevin Whelan 1,  Hussien Al-Shamma 1,  Joel Gatlin 1,  Minh Le 1,  Ibragim Gaidarov 1,  Todd Anthony 1,  David J Unett 1,  Anthony Blackburn 1,  Jaimie Rueter 1,  Scott Stirn 1,  Dominic P Behan 1,  Robert M Jones 1
Affiliations

Affiliation

  • 1 Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
PMID: 25516790 DOI: 10.1021/ml500389m
Abstract

APD334 was discovered as part of our internal effort to identify potent, centrally available, functional antagonists of the S1P1 receptor for use as next generation therapeutics for treating multiple sclerosis (MS) and other autoimmune diseases. APD334 is a potent functional antagonist of S1P1 and has a favorable PK/PD profile, producing robust lymphocyte lowering at relatively low plasma concentrations in several preclinical species. This new agent was efficacious in a mouse experimental autoimmune encephalomyelitis (EAE) model of MS and a rat collagen induced arthritis (CIA) model and was found to have appreciable central exposure.

Keywords

APD334; FTY720; S1P1; Sphingosine-1-phosphate; fingolimod; gilenya.

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