2. Academic Validation
  3. Discovery of ATR kinase inhibitor berzosertib (VX-970, M6620): Clinical candidate for cancer therapy

Discovery of ATR kinase inhibitor berzosertib (VX-970, M6620): Clinical candidate for cancer therapy

  • Pharmacol Ther. 2020 Jun;210:107518. doi: 10.1016/j.pharmthera.2020.107518.
Lukas Gorecki 1,  Martin Andrs 2,  Martina Rezacova 3,  Jan Korabecny 4
Affiliations

Affiliations

  • 1 Biomedical Research Center, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic.
  • 2 Biomedical Research Center, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic; Laboratory of Cancer Cell Biology, Institute of Molecular Genetics of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic.
  • 3 Department of Medical Biochemistry, Faculty of Medicine in Hradec Kralove, Charles University, Simkova 870, 500 38 Hradec Kralove, Czech Republic.
  • 4 Biomedical Research Center, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic. Electronic address: jan.korabecny@fnhk.cz.
PMID: 32109490 DOI: 10.1016/j.pharmthera.2020.107518
Abstract

Chemoresistance, radioresistance, and the challenge of achieving complete resection are major driving forces in the search for more robust and targeted Anticancer therapies. Targeting the DNA damage response has recently attracted research interest, as these processes are enhanced in tumour cells. The major replication stress responder is ATM and Rad3-related (ATR) kinase, which is attracting attention worldwide with four drug candidates currently in phase I/II clinical trials. This review addresses a potent and selective small-molecule ATR Inhibitor, which is known as VX-970 (also known as berzosertib or M6620), and summarizes the existing preclinical data to provide deep insight regarding its real potential. We also outline the transition from preclinical to clinical studies, as well as its relationships with other clinical candidates (AZD6738, VX-803 [M4344], and BAY1895344). The results suggest that VX-970 is indeed a promising Anticancer drug that can be used both as monotherapy and in combination with either chemotherapy or radiotherapy strategies. Based on patient anamnesis and biomarker identification, VX-970 could become a valuable tool for oncologists in the fight against Cancer.

Keywords

ATR kinase inhibitor; Berzosertib; DNA damage response; M6620; VX-970; cancer; drug development; replication stress.

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