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

Autor: De S; School of Chemical Sciences, National Institute of Science Education and Research (NISER), Bhubaneswar, An OCC of Homi Bhabha National Institute (HBNI), Khurda, Odisha 752050, India., Sahu R; College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea., Palei S; Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302, India., Narayan Nanda L; Chemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Harvard Medical School, Cambridge 02142, United States; P.G. Department of Chemistry, Government Autonomous College, Utkal University, Angul 759143, Odisha, India. Electronic address: lnnanda.gaca@gmail.com.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2024 Oct 01; Vol. 112, pp. 117875. Date of Electronic Publication: 2024 Aug 16.
DOI: 10.1016/j.bmc.2024.117875
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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