Recommended Tool Compounds: Thienotriazolodiazepines-Derivatized Chemical Probes to Target BET Bromodomains

Abstract

Thienotriazolodiazepines, including (+)-JQ1 (4), are well-known inhibitors of the bromodomain (BD) and extra-terminal domain (BET) family of proteins. Despite the suboptimal physicochemical properties as a drug candidate, such as poor solubility and half-life, (+)-JQ1 (4) has proven as an effective chemical probe with high target potency and selectivity. (+)-JQ1 (4) and (+)-JQ1-derived chemical probes have played a vital role in chemical biology and drug discovery over the past decade, which is demonstrated by the high number of impactful research studies published since the disclosure of (+)-JQ1 (4) in 2010. In this review, we discuss the development of (+)-JQ1-derivatized chemical probes over the past decade and their significant contribution to scientific research. Specifically, we will summarize the development of innovative label-free and labeled (+)-JQ1-derivatized chemical probes, such as bivalent, covalent, and photoaffinity probes as well as protein degraders, with a focus on the design of these chemical probes.