ACT-001(Accendatech)

Primary central nervous system lymphoma (PCNSL) is a group of malignant brain tumors with a poor prognosis, and new therapeutic approaches for this tumor urgently need to be investigated. Formulated from a long-standing anti-inflammatory drugs, ACT001 has demonstrated in clinical research to be able to pass through the blood-brain barrier (BBB) and affect the central nervous system. The effects of ACT001 on PCNSL cell apoptosis, proliferation and immune-related indexes were detected by flow cytometry, and the efficacy of ACT001 was verified in vivo by constructing a mouse PCNSL tumor model. ACT001 significantly inhibited PCNSL cell proliferation and induced apoptosis in vitro. In addition, ACT001 can significantly inhibit the PD-1/PD-L1 expression and restore the function of T cells, so that the immune system cannot allow tumor cells to escape. In vivo experiments show that co-infusion of ACT001 and T cells effectively inhibits PCNSL tumor growth in NSG mice. Our work describes the inhibitory effect of ACT001 on the PCNSL cell line and demonstrated the inhibitory effect of ACT001 on immune checkpoints.

The increasing side effects of traditional medications used to treat type II diabetes have made research into the development of safer and more effective natural medications necessary. ACT001, a derivative of parthenolide, has been shown to have good anti-inflammatory and antitumor effects; however, its role in diabetes is unclear. The short-chain fatty acid propionate is a common food preservative that has been found to cause disturbances in glucose metabolism in mice and humans. This study aimed to investigate whether sodium propionate could aggravate insulin resistance in obese mice and cause diabetes and to study the alleviative effects and potential mechanisms of action of ACT001 on insulin resistance in diabetic mice. Type II diabetic mice were adminietered sodium propionate combined with a high-fat diet (HFD + propionate) by gavage daily for four weeks. Biochemical analysis showed that ACT001 significantly affected blood glucose concentration in diabetic mice, mainly by downregulating the expression of phosphoenolpyruvate carboxykinase 2 and glucose-6-phosphatase. Meanwhile, the level of fatty acid-binding protein 4 in the liver was significantly decreased. ACT001 has a protective effect on the liver and adipose tissue of mice. In addition, the results of the running wheel experiment indicated that ACT001 alleviated the circadian rhythm disorder caused by insulin resistance to a certain extent. This study revealed the potential mechanism by which ACT001 alleviates insulin resistance and provides ideas for developing natural antidiabetic drugs.