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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.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2016 Mar 01; Vol. 26 (5), pp. 1365-70. Date of Electronic Publication: 2016 Feb 02. - Publication Year :
- 2016
-
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.<br /> (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Subjects :
- Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Azepines chemical synthesis
Azepines chemistry
CD28 Antigens immunology
Cell Line, Tumor
Cell Proliferation drug effects
Cell Survival drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Histone Acetyltransferases
Histone Chaperones
Humans
Immunosuppressive Agents chemical synthesis
Immunosuppressive Agents chemistry
Molecular Structure
Nuclear Proteins antagonists & inhibitors
Nuclear Proteins metabolism
Phenotype
Structure-Activity Relationship
T-Lymphocytes immunology
T-Lymphocytes metabolism
Antineoplastic Agents pharmacology
Azepines pharmacology
CD28 Antigens metabolism
Drug Discovery
Immunosuppressive Agents pharmacology
T-Lymphocytes cytology
T-Lymphocytes drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 26
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 26869194
- Full Text :
- https://doi.org/10.1016/j.bmcl.2016.01.084