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. Issue 5 (1st March 2016)

• Record Type: Journal Article
• Authors: Endo, Junichi; Hikawa, Hidemasa; Hamada, Maiko; Ishibuchi, Seigo; Fujie, Naoto; Sugiyama, Naoki; Tanaka, Minoru; Kobayashi, Haruhito; Sugahara, Kunio; Oshita, Koichi; Iwata, Kazunori; Ooike, Shinsuke; Murata, Meguru; Sumichika, Hiroshi; Chiba, Kenji; Adachi, Kunitomo
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 5(2016)
• Page Start: 1365
• Page End: 1370
• Publication Date: 2016-03-01
• Subjects: CD28 -- Phenotypic drug discovery -- Chemical biology -- BET family -- Bromodomain -- Immunosuppressant -- Anti-cancer; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.01.084
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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 that7f is a first inhibitor of epigenetic bromodomain-containing proteins.7f is expected to become an anti-cancer agent as well as an immunosuppressive agent.