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

Autor: Weichao Chen, Andrew M. Kawasaki, Dominic P. Behan, Jeff Edwards, You-An Ma, Tawfik Gharbaoui, Sun Hee Kim, Jayant Thatte, Hussien A. Al-Shamma, Carleton R. Sage, Jeremy Barden, Anthony C. Blackburn, Michelle Solomon, Xiuwen Zhu, Christopher Ronald J, David Mills, Ibragim Gaidarov, Antonio Garrido Montalban, Sangdon Han, Luis Lopez, Dipanjan Sengupta, Michael Morgan, Juerg Lehmann, Daniel J. Buzard, Graeme Semple, Kevin Whelan, Yinghong Gao, Joel Gatlin, Moody Jeanne, David J. Unett, Imelda Calderon, Lars Thoresen, Robert M. Jones, Brett Ullman, Todd Anthony, Chuan Chen, Minh Le, Khawja A. Usmani, Scott Stirn, Jaimie Karyn Rueter, Lixia Fu, Lorene Calvano, Abu J.M. Sadeque
Rok vydání: 2014
Předmět:
Zdroj: ACS Medicinal Chemistry Letters. 5:1313-1317
ISSN: 1948-5875
Popis: 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.
Databáze: OpenAIRE