A phenotypic drug discovery study on thienodiazepine derivatives as inhibitors of T cell proliferation induced by CD28 co-stimulation leads to the dis...

Basic Information

ID: ALA3769406

Journal: Bioorg Med Chem Lett

Title: A phenotypic drug discovery study on thienodiazepine derivatives as inhibitors of T cell proliferation induced by CD28 co-stimulation leads to the discovery of a first bromodomain inhibitor.

Authors: Endo J, Hikawa H, Hamada M, Ishibuchi S, Fujie N, Sugiyama N, Tanaka M, Kobayashi H, Sugahara K, Oshita K, Iwata K, Ooike S, Murata M, Sumichika H, Chiba K, Adachi K.

Abstract: A phenotypic screening of thienodiazepines derived from a hit compound found through a binding assay targeting co-stimulatory molecules on T cells and antigen presenting cells successfully led to the discovery of a thienotriazolodiazepine compound (7f) possessing potent immunosuppressive activity. A chemical biology approach has succeeded in revealing that 7f is a first inhibitor of epigenetic bromodomain-containing proteins. 7f is expected to become an anti-cancer agent as well as an immunosuppressive agent.

CiteXplore: 26869194

DOI: 10.1016/j.bmcl.2016.01.084

Patent ID: