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

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.

 

Comments:

The review you mentioned discusses VX-970 (also known as berzosertib or M6620), a small-molecule inhibitor that targets the ATM and Rad3-related (ATR) kinase. ATR is a key player in the DNA damage response and is overactive in tumor cells, contributing to chemoresistance and radioresistance.

The review highlights that VX-970 has shown promise as a potent and selective ATR inhibitor. It summarizes preclinical data that supports its potential as an anticancer therapy. The drug is currently undergoing phase I/II clinical trials, along with three other ATR inhibitors: AZD6738, VX-803 (M4344), and BAY1895344.

The results from preclinical studies suggest that VX-970 could be an effective anticancer drug, both as a standalone treatment and in combination with chemotherapy or radiotherapy. By targeting ATR, it aims to disrupt the DNA damage response in cancer cells, potentially enhancing the effectiveness of existing treatments. The review also suggests that VX-970 could be used in personalized medicine approaches, where patient history and biomarker identification could help identify individuals who would benefit most from the drug.

Overall, the review indicates that VX-970 has the potential to become a valuable tool for oncologists in the battle against cancer, and its progression from preclinical studies to clinical trials is an important step towards evaluating its safety and efficacy in human patients.

Related Products

Cat.No.	Product Name	Information
S9639	VX-803 (M4344)	VX-803 (M4344, ATR inhibitor 2) is an ATP-competitive, orally active, and selective inhibitor of ataxia telangiectasia and Rad3 related (ATR) kinase with Ki of < 150 pM. VX-803 (M4344) potently inhibits ATR-driven phosphorylated checkpoint kinase-1 (P-Chk1) phosphorylation with IC50 of 8 nM. VX-803 (M4344) exhibits potential antineoplastic activity.

Related Targets

ATM/ATR Chk