Pharmacodynamic and Toxicity Studies of 6-Isopropyldithio-2′-guanosine Analogs in Acute T-Lymphoblastic Leukemia
Simple SummaryAcute T-lymphoblastic leukemia is a disease with a very low survival rate after relapse, and the search for new therapeutic agents is important for the clinical benefit of patients with acute T-lymphoblastic leukemia. Our study developed YLS010, a small molecule that is more sensitive to acute T-lymphoblastic leukemia cells, based on the structure of the invented small molecule YLS004. This novel small molecule demonstrated good antitumor activity in vivo and in vitro with acceptable toxicity. These findings provide a new avenue for the development of clinical drugs for patients with acute T-lymphoblastic leukemia.Abstract(1) Background: The research group has developed a new small molecule, 6-Isopropyldithio-2′-deoxyguanosine analogs-YLS004, which has been shown to be the most sensitive in acute T-lymphoblastic leukemia cells. Moreover, it was found that the structure of Nelarabine, a drug used to treat acute T-lymphoblastic leukemia, is highly similar to that of YLS004. Consequently, the structure of YLS004 was altered to produce a new small molecule inhibitor for this study, named YLS010. (2) Results: YLS010 has exhibited potent anti-tumor effects by inducing cell apoptosis and ferroptosis. A dose gradient was designed for in vivo experiments based on tentative estimates of the toxicity dose using acute toxicity in mice and long-term toxicity in rats. The study found that YLS010 at a dose of 8 mg/kg prolonged the survival of late-stage acute T-lymphoblastic leukemia mice in the mouse model study. (3) Conclusions: YLS010 has demonstrated specific killing effects against acute T-lymphoblastic leukemia both in vivo and in vitro. Preclinical studies of YLS010 offer a new opportunity for the treatment of patients with acute T-lymphoblastic leukemia in clinical settings.
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