66909-27-1Relevant articles and documents
Discovery of a Potent and Selective ATAD2 Bromodomain Inhibitor with Antiproliferative Activity in Breast Cancer Models
Winter-Holt, Jon J.,Bardelle, Catherine,Chiarparin, Elisabetta,Dale, Ian L.,Davey, Paul R. J.,Davies, Nichola L.,Denz, Christopher,Fillery, Shaun M.,Guérot, Carine M.,Han, Fujin,Hughes, Samantha J.,Kulkarni, Meghana,Liu, Zhaoqun,Milbradt, Alexander,Moss, Thomas A.,Niu, Huijun,Patel, Joe,Rabow, Alfred A.,Schimpl, Marianne,Shi, Junjie,Sun, Dongqing,Yang, Dejian,Guichard, Sylvie
, p. 3306 - 3331 (2022/02/23)
ATAD2 is an epigenetic bromodomain-containing target which is overexpressed in many cancers and has been suggested as a potential oncology target. While several small molecule inhibitors have been described in the literature, their cellular activity has proved to be underwhelming. In this work, we describe the identification of a novel series of ATAD2 inhibitors by high throughput screening, confirmation of the bromodomain region as the site of action, and the optimization campaign undertaken to improve the potency, selectivity, and permeability of the initial hit. The result is compound 5 (AZ13824374), a highly potent and selective ATAD2 inhibitor which shows cellular target engagement and antiproliferative activity in a range of breast cancer models.
PYRIDINONES
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Page/Page column 44; 45; 46; 47; 48, (2015/02/25)
The present invention encompasses compounds of general formula (I) wherein the groups R1 to R3 and X1 through X6 have the meanings given in the claims and in the specification. The compounds of the invention are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation pharmaceutical preparations containing such compounds and their uses as a medicament.
