Synthesis, SAR, and application of JQ1 analogs as PROTACs for cancer therapy.

[Display omitted] • First extensive review on the synthesis and anti-cancer activity of (+)-JQ1 analogs are discussed. • SAR of the (+)-JQ1 scaffolds are also demonstrated. • Application of JQ1 scaffolds in PROTAC technology has been presented. • Mechanism of protein degradation by PROTACs are explained. • Challenges of PROTAC for medicinal chemists are also outlined. JQ1 is a wonder therapeutic molecule that selectively inhibits the BRD4 signaling pathway and is thus widely used in the anticancer drug discovery program. Due to its unique selective BRD4 binding property, its applications are further extended in the design and synthesis of bi-functional PROTAC molecules. This BRD4 targeting PROTAC molecule selectively degrades the protein by proteolysis. There are several modifications of JQ1 known to date and extensively explored for their applications in PROTAC technology by several research groups in academia as well as industry for targeting oncogenic genes. In this review, we have covered the discovery and synthesis of the JQ1 molecule. The SAR of the JQ1 analogs will help researchers develop potent JQ1 compounds with improved inhibitory properties against malignant cells. Furthermore, we explored the potential application of JQ1 analogs in PROTAC technology. The brief history of the bromodomain family of proteins, as well as the obstacles connected with PROTAC technology, can help comprehend the context of the current research, which has the potential to improve the drug development process. Overall, this review comprehensively appraises JQ1 molecules and their prior implementation in PROTAC technology and cancer therapy. [ABSTRACT FROM AUTHOR]