Discovery of ATR kinase inhibitor berzosertib (VX-970, M6620): Clinical candidate for cancer therapy
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't, Review
PubMed
32109490
DOI
10.1016/j.pharmthera.2020.107518
PII: S0163-7258(20)30046-2
Knihovny.cz E-resources
- Keywords
- ATR kinase inhibitor, Berzosertib, DNA damage response, M6620, VX-970, cancer, drug development, replication stress,
- MeSH
- Ataxia Telangiectasia Mutated Proteins antagonists & inhibitors metabolism MeSH
- Molecular Targeted Therapy MeSH
- Protein Kinase Inhibitors adverse effects therapeutic use MeSH
- Isoxazoles adverse effects therapeutic use MeSH
- Humans MeSH
- Neoplasms drug therapy enzymology pathology MeSH
- Drug Discovery * MeSH
- Antineoplastic Agents adverse effects therapeutic use MeSH
- Antineoplastic Combined Chemotherapy Protocols therapeutic use MeSH
- Pyrazines adverse effects therapeutic use MeSH
- Signal Transduction MeSH
- Sulfones therapeutic use MeSH
- Drug Synergism MeSH
- Treatment Outcome MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- 3-amino-6-(4-(methylsulfonyl)phenyl)-N-phenylpyrazine-2-carboxamide MeSH Browser
- Ataxia Telangiectasia Mutated Proteins MeSH
- ATR protein, human MeSH Browser
- berzosertib MeSH Browser
- Protein Kinase Inhibitors MeSH
- Isoxazoles MeSH
- Antineoplastic Agents MeSH
- Pyrazines MeSH
- Sulfones MeSH
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.
References provided by Crossref.org
Clinical Candidates Targeting the ATR-CHK1-WEE1 Axis in Cancer
