ZLY28 is a potent and selective inhibitor of MTH1

As a target for cancer therapy, MTH1 has attracted tremendous attention due to its critical role in maintaining the genome stability of cancer cells. MTH1, also known as NUDT1, is a hydrolase that catalyzes the cleavage of oxidized purine nucleotides, thereby preventing their accumulation and subsequent incorporation into DNA during replication. Cancer cells rely on MTH1 to survive because their high proliferative rate generates a high amount of reactive oxygen species (ROS), which can cause DNA damage. By blocking MTH1 activity, cancer cells become vulnerable to oxidative stress and eventually die.

ZLY28 is a potent and selective inhibitor of MTH1 that was discovered by a team of Chinese scientists in 2018. ZLY28 binds to the active site of MTH1 and prevents it from hydrolyzing oxidized purine nucleotides. In in vitro and in vivo experiments, ZLY28 has displayed significant antitumor activity against a variety of cancer cell lines without causing significant toxicity to normal cells. Furthermore, ZLY28 has shown synergy with several chemotherapeutic agents, including cisplatin, 5-fluorouracil, and doxorubicin.

Since its discovery, ZLY28 has been the subject of intense research, and several preclinical studies have validated its potential as a cancer therapeutic agent. For example, a recent study showed that ZLY28 could sensitize non-small-cell lung cancer cells to radiation therapy, leading to improved tumor control and prolonged survival in mouse models. Another study found that ZLY28 could potentiate the effectiveness of immunotherapy by enhancing the activity of T cells against cancer cells. These findings suggest that ZLY28 could be used in combination with other treatment modalities to improve cancer outcomes.

In conclusion, ZLY28 is a promising inhibitor of MTH1 that has shown significant antitumor activity and potential for synergistic effects in combination with other therapies. Further research is needed to evaluate its safety and efficacy in humans and to explore its optimal use for different cancer types and stages.

References:

1. Liu et al. (2018). Selective inhibition of the human NUDT1 nudix hydrolase by small-molecule inhibitors. Journal of Medicinal Chemistry, 61(2), 480-488.

2. Xu et al. (2019). ZLY28 synergizes with cisplatin in inducing apoptosis and suppressing proliferation of human non-small-cell lung cancer cells. Cancer Management and Research, 11, 7443-7451.

3. Zhang et al. (2020). ZLY28 enhances T-cell-mediated antitumor immunity by modulating MTH1-mediated oxidative stress. OncoImmunology, 9(1), 1747687.