| Literature DB >> 12672234 |
Daniel R Goldberg1, Tanja Butz, Mario G Cardozo, Robert J Eckner, Abdelhakim Hammach, Jessica Huang, Scott Jakes, Suresh Kapadia, Mohammed Kashem, Susan Lukas, Tina M Morwick, Maret Panzenbeck, Usha Patel, Susan Pav, Gregory W Peet, Jeffrey D Peterson, Anthony S Prokopowicz, Roger J Snow, Rosemarie Sellati, Hidenori Takahashi, Jonathan Tan, Matt A Tschantz, Xiao-Jun Wang, Yong Wang, John Wolak, Pla Xiong, Neil Moss.
Abstract
The tyrosine kinase p56lck (lck) is essential for T cell activation; thus, inhibitors of lck have potential utility as autoimmune agents. Our initial disclosure of a new class of lck inhibitors based on the phenylaminoimidazoisoquinolin-9-one showed reasonable cellular activity but did not work in vivo upon oral administration. Our current work highlights the further use of rational drug design and molecular modeling to produce a series of lck inhibitors that demonstrate cellular activity below 100 nM and are as efficacious as cyclosporin A in an in vivo mouse model of anti-CD3-induced IL-2 production.Entities:
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Year: 2003 PMID： 12672234 DOI： 10.1021/jm020446l
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446