Discovery of a Novel Bromodomain and Extra Terminal Domain (BET) Protein Inhibitor, I-BET282E, Suitable for Clinical Progression.

Basic Information

ID: ALA4842350

Journal: J Med Chem

Title: Discovery of a Novel Bromodomain and Extra Terminal Domain (BET) Protein Inhibitor, I-BET282E, Suitable for Clinical Progression.

Authors: Jones KL, Beaumont DM, Bernard SG, Bit RA, Campbell SP, Chung CW, Cutler L, Demont EH, Dennis K, Gordon L, Gray JR, Haase MV, Lewis AJ, McCleary S, Mitchell DJ, Moore SM, Parr N, Robb OJ, Smithers N, Soden PE, Suckling CJ, Taylor S, Walker AL, Watson RJ, Prinjha RK.

Abstract: The functions of the bromodomain and extra terminal (BET) family of proteins have been implicated in a wide range of diseases, particularly in the oncology and immuno-inflammatory areas, and several inhibitors are under investigation in the clinic. To mitigate the risk of attrition of these compounds due to structurally related toxicity findings, additional molecules from distinct chemical series were required. Here we describe the structure- and property-based optimization of the in vivo tool molecule I-BET151 toward I-BET282E, a molecule with properties suitable for progression into clinical studies.

CiteXplore: 34387088

DOI: 10.1021/acs.jmedchem.1c00855

Patent ID: