title: Discovery of APD334: Design of a Clinical Stage Functional Antagonist of the Sphingosine-1-phosphate-1 Receptor.
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.
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Buzard
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Luis
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authors.lastname: Lopez
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kawasaki
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Xiuwen
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Moody
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Lars
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authors.lastname: Thoresen
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Imelda
authors.initials: I
authors.lastname: Calderon
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Brett
authors.initials: B
authors.lastname: Ullman
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Sangdon
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authors.lastname: Han
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Juerg
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authors.lastname: Lehmann
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Tawfik
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authors.lastname: Gharbaoui
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Dipanjan
authors.initials: D
authors.lastname: Sengupta
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Lorene
authors.initials: L
authors.lastname: Calvano
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Antonio Garrido
authors.initials: AG
authors.lastname: Montalban
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: You-An
authors.initials: YA
authors.lastname: Ma
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Carleton
authors.initials: C
authors.lastname: Sage
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Yinghong
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authors.lastname: Gao
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Graeme
authors.initials: G
authors.lastname: Semple
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Jeff
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authors.lastname: Edwards
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
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authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Michael
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authors.lastname: Morgan
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Weichao
authors.initials: W
authors.lastname: Chen
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Khawja
authors.initials: K
authors.lastname: Usmani
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Chuan
authors.initials: C
authors.lastname: Chen
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Abu
authors.initials: A
authors.lastname: Sadeque
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Christopher
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Jayant
authors.initials: J
authors.lastname: Thatte
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Lixia
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authors.lastname: Fu
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Michelle
authors.initials: M
authors.lastname: Solomon
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: David
authors.initials: D
authors.lastname: Mills
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Kevin
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authors.lastname: Whelan
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Hussien
authors.initials: H
authors.lastname: Al-Shamma
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Joel
authors.initials: J
authors.lastname: Gatlin
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Minh
authors.initials: M
authors.lastname: Le
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Ibragim
authors.initials: I
authors.lastname: Gaidarov
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Todd
authors.initials: T
authors.lastname: Anthony
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: David J
authors.initials: DJ
authors.lastname: Unett
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Anthony
authors.initials: A
authors.lastname: Blackburn
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Jaimie
authors.initials: J
authors.lastname: Rueter
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Scott
authors.initials: S
authors.lastname: Stirn
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Dominic P
authors.initials: DP
authors.lastname: Behan
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Jones
keywords: APD334; FTY720; S1P1; Sphingosine-1-phosphate; fingolimod; gilenya