2. Academic Validation
  3. Multi-therapies Based on PARP Inhibition: Potential Therapeutic Approaches for Cancer Treatment

Multi-therapies Based on PARP Inhibition: Potential Therapeutic Approaches for Cancer Treatment

  • J Med Chem. 2022 Dec 22;65(24):16099-16127. doi: 10.1021/acs.jmedchem.2c01352.
Jie Zhang 1,  Yuqi Gao 2 3,  Zipeng Zhang 3,  Jinbo Zhao 1 4,  Wenshuang Jia 3,  Chengcai Xia 1,  Fugang Wang 5,  Tingting Liu 1
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, School of Pharmacy, Shandong First Medical University and Shandong Academy of Medical Sciences, Taian, Shandong 271016, China.
  • 2 College of Radiology, Shandong First Medical University and Shandong Academy of Medical Sciences, Taian, Shandong 271016, China.
  • 3 Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan, Shandong 250117, China.
  • 4 Department of Chemistry and Biology, Jilin Provincial Key Laboratory of Carbon Fiber Development and Application, Changchun University of Technology, Changchun, Jilin 130012, China.
  • 5 Department of Pharmacology, School of Pharmacy, Shandong First Medical University and Shandong Academy of Medical Sciences, Taian, Shandong 271016, China.
PMID: 36512711 DOI: 10.1021/acs.jmedchem.2c01352
Abstract

The nuclear Enzymes called poly(ADP-ribose)polymerases (PARPs) are known to catalyze the process of PARylation, which plays a vital role in various cellular functions. They have become important targets for the discovery of novel antitumor drugs since their inhibition can induce significant lethality in tumor cells. Therefore, researchers all over the world have been focusing on developing novel and potent PARP inhibitors for Cancer therapy. Studies have shown that PARP inhibitors and Other antitumor agents, such as EZH2 and EGFR inhibitors, play a synergistic role in Cancer cells. The combined inhibition of PARP and the targets with synergistic effects may provide a rational strategy to improve the effectiveness of current Anticancer regimens. In this Perspective, we sum up the recent advance of PARP-targeted agents, including single-target inhibitors/degraders and dual-target inhibitors/degraders, discuss the fundamental theory of developing these dual-target agents, and give insight into the corresponding structure-activity relationships of these agents.

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