An Overview of ATR
Ataxia telangiectasia mutant gene Rad3 associated kinase (ATR) is an important regulatory factor for the mechanism of DNA damage repair (DDR). ATR is a member of phosphatidylinositol 3-kinase associated kinase protein family. It consists of 2644 amino acids, and its N-terminal is ATR interaction protein (ATR-interacting-protein, ATRIP) binding domain, which is an important domain activated by ATR. It has been found that ATR molecular pathways regulate DNA damage and repair through a variety of cytokines, leading to the development of normal cells into tumor cells. Some of these inhibitors have shown significant anti-tumor effects and have entered clinical trials.
Inhibition of ATR
At present, many ATR inhibitors have been reported, such as VX-970 and AZD6738. According to the structural characteristics of the existing ATR inhibitors, the inhibitors can be classified into pyrimidines, pyrazines and pyridines. In addition to the representative compounds mentioned above, it was found that other inhibitors including caffeine, schisandrin B, wortmannin and so on, had inhibitory effects on ATR. Caffeine can interfere with the cell cycle arrest and breakdown induced by DNA damage. The mechanism of DNA damage response promotes tumor cell death.
ATR and diseases
As a mechanism of DNA damage response, ATR pathway plays an important role in tumor survival. The inhibition of ATR, a key factor, can induce the death of ATR pathway dependent malignant tumor cells and have little effect on the reproduction and growth of normal cells. It is an ideal target for the development of low toxicity and high efficiency targeted antitumor drugs. The results showed that ATR was mainly blocked by cell cycle progression. Stable replication forks and promoting DNA repair to promote cell survival. ATR inhibitors alone or in conjunction with other antitumor drugs have a strong inhibitory effect on ATR dependent tumor cells. Therefore, selective inhibition of ATR provides a new approach to limping treatment and a new tool for tumor research.
Products for ATR