A research team led by Prof. LIU Qingsong from the Hefei Institutes of Physical Science of the Chinese Academy of Sciences has developed a novel Mammalian STE20-like protein 1 kinase (MST1) inhibitor for the treatment of type 1 diabetes (T1D) and type 2 diabetes (T2D).

Relevant results were published in Journal of Medicinal Chemistry.

Currently, nearly 350 million people worldwide suffer from diabetes. Although with different etiologies, both T1D and T2D will cause the damage of β cells and disordered insulin-secretion function of β cells. Therefore, it is important to develop new approaches to achieve the goal of increasing the mass as well as improving the function of β cells.

It has been reported that MST1 plays an important role in β-cell apoptosis and insulin secretion, which is a new therapeutic target for β cell protection.

In this study, using a structure-directed drug design approach, scientists have identified a powerful, highly selective MST1 inhibitor (IHMT-MST1-58) that shows a number of advantages.

The compound could inhibit the phosphorylation of MST1 and protect β cells from inflammatory cytokines in vitro. And it also exhibited good in vivo pharmacokinetic properties among different species including rats, mice, and beagle dogs.

Both monotherapy of IHMT-MST1-58 and in combination with metformin could decrease the fasting blood glucose level and protect β cells in the streptozotocin (STZ)-induced type 1/2 diabetes mouse models. Furthermore, coadministration of IHMT-MST1-58 with metformin also reduced the hemoglobin A1c (HbA1c) level.

This study provides a new potential therapeutic candidate for diabetes and it was supported by the National Natural Science Foundation of China.

Antidiabetic efficacy of IHMT-MST1-58 (19), metformin, and combo in the T1D and T2D mouse models. (Image by WANG Beilei)