Discovery of ATR kinase inhibitor berzosertib (VX-970, M6620): Clinical candidate for cancer therapy
Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem, přehledy
PubMed
32109490
DOI
10.1016/j.pharmthera.2020.107518
PII: S0163-7258(20)30046-2
Knihovny.cz E-zdroje
- Klíčová slova
- ATR kinase inhibitor, Berzosertib, DNA damage response, M6620, VX-970, cancer, drug development, replication stress,
- MeSH
- ATM protein antagonisté a inhibitory metabolismus MeSH
- cílená molekulární terapie MeSH
- inhibitory proteinkinas škodlivé účinky terapeutické užití MeSH
- isoxazoly škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- nádory farmakoterapie enzymologie patologie MeSH
- objevování léků * MeSH
- protinádorové látky škodlivé účinky terapeutické užití MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- pyraziny škodlivé účinky terapeutické užití MeSH
- signální transdukce MeSH
- sulfony terapeutické užití MeSH
- synergismus léků MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- 3-amino-6-(4-(methylsulfonyl)phenyl)-N-phenylpyrazine-2-carboxamide MeSH Prohlížeč
- ATM protein MeSH
- ATR protein, human MeSH Prohlížeč
- berzosertib MeSH Prohlížeč
- inhibitory proteinkinas MeSH
- isoxazoly MeSH
- protinádorové látky MeSH
- pyraziny MeSH
- sulfony 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.
Citace poskytuje Crossref.org
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