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

Autor: Koichi Oshita, Shinsuke Ooike, Kunitomo Adachi, Naoto Fujie, Kunio Sugahara, Hidemasa Hikawa, Endo Junichi, Naoki Sugiyama, Kazunori Iwata, Maiko Hamada, Seigo Ishibuchi, Meguru Murata, Kenji Chiba, Haruhito Kobayashi, Minoru Tanaka, Hiroshi Sumichika
Rok vydání: 2015
Předmět:
0301 basic medicine
Cell Survival
T cell
Phenotypic screening
T-Lymphocytes
Clinical Biochemistry
Pharmaceutical Science
Antineoplastic Agents
Pharmacology
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
Structure-Activity Relationship
0302 clinical medicine
CD28 Antigens
Cell Line
Tumor
Drug Discovery
medicine
Humans
Histone Chaperones
Antigen-presenting cell
Molecular Biology
Cell Proliferation
Histone Acetyltransferases
Dose-Response Relationship
Drug
Molecular Structure
Drug discovery
Organic Chemistry
CD28
Nuclear Proteins
Azepines
Bromodomain
030104 developmental biology
medicine.anatomical_structure
Phenotype
chemistry
030220 oncology & carcinogenesis
Thienodiazepine
Molecular Medicine
Classical pharmacology
Drug Screening Assays
Antitumor
Immunosuppressive Agents
Zdroj: Bioorganicmedicinal chemistry letters. 26(5)
ISSN: 1464-3405
Popis: 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.
Databáze: OpenAIRE
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